title: Cohorte Non Interventionnelle Ambispective Nationale Multicentrique de Patients Suivis Pour Cancer et infectés Par le SARS-CoV-2

summary:
Since December 2019, China and then the rest of the world have been affected by the rapid development of a new coronavirus, SARS-CoV-2 (severe acute respiratory syndrome corona virus 2). The disease caused by this coronavirus (COVID-19), which is transmitted by air via droplets, is potentially responsible for a severe respiratory syndrome but also for a multivisceral deficiency that can lead to death.

Cancer patients are generally more susceptible to infections than people without cancer due to immunosuppression caused by their tumor disease and/or conventional anti-cancer treatments used such as cytotoxic chemotherapy, several targeted therapies, radiotherapy or recent surgery. These patients may therefore be at particular risk for COVID-19.

This is suggested by the very first analysis on the subject, which reports data from the Chinese prospective database of 2007 patients with proven COVID-19 infection in 575 hospitals in 31 Chinese provinces. The authors of this publication conclude with 3 measures to be proposed to patients undergoing cancer follow-up: 1/ consider postponing adjuvant chemotherapy or surgery in the case of localized and stable cancer, 2/ reinforce protective measures for these patients, and 3/ monitor very closely and treat these patients more intensively when they have a COVID-19.

However, the increased risk of SARS-CoV-2 infection and severe forms of COVID-19 in cancer patients suggested by this first study remains to be demonstrated given its limitations, already highlighted by other authors. Indeed, the number of patients is small and the population of cancer patients is very heterogeneous, with in particular 12 patients out of 16 who had recovered from initial cancer treatments (therefore without immunosuppression), half of whom had a disease course of more than 4 years.

Nevertheless, a second Chinese study has just recently been published, reporting COVID-19 data among 1524 cancer patients admitted between December 30, 2019 and February 17, 2020 in the Department of Radiotherapy and Medical Oncology of the University Hospital of Wuhan, the source city of the COVID-19 epidemic. Although the rate of CoV-2 SARS infection was lower than that reported in the first study, it was still 0.79% (n=12), which is much higher than the rate of COVID-19 diagnosed in Wuhan City during the same period (0.37%, 41 152/11 081 000). Again, lung cancer was the main tumour location observed in 7 patients (58%), of which 5 (42%) were undergoing chemotherapy +/- immunotherapy. Three deaths (25%) were reported. Patients over 60 years of age with lung cancer had a higher incidence of COVID-19 (4.3% vs. 1.8%). Thus, it appears that the risk of COVID-19 is actually increased in cancer patients, although again, less than half of the patients with lung cancer had a higher incidence of COVID-19.

Moreover, two more recent studies performed in patients treated in Hubei Province of China and in New-York city found that patients with cancer had significantly increased risk of death compared to non-cancer COVID-19 patients, especially patients with metastatic cancer and those who had recent surgery.

Therefore, many questions remain to date on the level of risk and the severity of COVID-19 in patients with active cancer, in particular those under anti-cancer treatment and in patients recently operated for localized cancer.

location_facility: PRIVE - Clinique Mutualiste de l'Estuaire

location_facility: CH - Germon et Gauthier - Service de Gastroentérologie

location_facility: ICAN - Institut de Cancérologie de Strasbourg Europe

location_facility: PRIVE - Institut de Cancérologie de Bourgogne GRReCC

location_facility: CHR - Centre Hospitalier Régional La Source

location_facility: PRIVE - La Louvière Institut de Cancérologie Lille Métropole

location_facility: CH - GHI de l'Est Francilien Site de Meaux

location_facility: Groupe Hospitalier Diaconesses Croix Saint Simon


title: Hospital Registry of Acute Myocarditis: Evolution of the Proportion of Positive SARS-COV-2 Cases During the Covid-19 Pandemic, Case Characteristics and Prognoses

acronym: MYOCOVID

summary: To date, the effects of SARS-Cov-2 (Covid-19) on the myocardium and the role it plays in the evolution towards an acute myocarditis are badly understood. The current pandemic of this emerging virus is an opportunity to assess the proportion of acute myocarditis attributable to SARS-Cov-2(Covid-19) and to assess the clinical, biological and imaging presentations, by means of a national prospective multicentre hospital registry of cases of acute myocarditis.

study_start_date_type: Actual

status: Unknown status

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Prospective

enrollment_type: Anticipated

lead_sponsor: University Hospital, Toulouse

location_country: France Mayotte Martinique Réunion

location_facility: Marie Lannelongue Hospital - Pediatric Cardiology

location_facility: Robert Debré Hospital - Pediatric cardiology

intervention_type: Diagnostic Test

lead_sponsor_type: academique

status_simplified: Unknown


title: Characterization of Fungal Infections in COVID-19 Infected and Mechanically Ventilated Patients in ICU

acronym: MY-CO-VID

summary: Characterization of fungal infections in COVID-19 infected and mechanically ventilated patients in ICU

status: Completed

study_completion_date_type: Actual

time_perspective: Other

enrollment_type: Actual

ReferenceType: derived

ReferenceCitation: Gangneux JP, Dannaoui E, Fekkar A, Luyt CE, Botterel F, De Prost N, Tadié JM, Reizine F, Houzé S, Timsit JF, Iriart X, Riu-Poulenc B, Sendid B, Nseir S, Persat F, Wallet F, Le Pape P, Canet E, Novara A, Manai M, Cateau E, Thille AW, Brun S, Cohen Y, Alanio A, Mégarbane B, Cornet M, Terzi N, Lamhaut L, Sabourin E, Desoubeaux G, Ehrmann S, Hennequin C, Voiriot G, Nevez G, Aubron C, Letscher-Bru V, Meziani F, Blaize M, Mayaux J, Monsel A, Boquel F, Robert-Gangneux F, Le Tulzo Y, Seguin P, Guegan H, Autier B, Lesouhaitier M, Pelletier R, Belaz S, Bonnal C, Berry A, Leroy J, François N, Richard JC, Paulus S, Argaud L, Dupont D, Menotti J, Morio F, Soulié M, Schwebel C, Garnaud C, Guitard J, Le Gal S, Quinio D, Morcet J, Laviolle B, Zahar JR, Bougnoux ME. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study. Lancet Respir Med. 2022 Feb;10(2):180-190. doi: 10.1016/S2213-2600(21)00442-2. Epub 2021 Nov 26.

lead_sponsor: Rennes University Hospital

location_facility:
CHU Strasbourg
CHU Lille
CHU Angers
Hôpital Lariboisière/ St Louis
CHU Toulouse
CHU Marseille
CHU Paris - Avicenne
CHU Rennes
CHU Paris - Bichat
CHU Paris - Mondor
CHU Tours
CHU Paris - HEGP
CHU de Nice
CHU Poitiers
CHU Grenoble
Hôpital Necker-Enfants Malades
CHU Nantes
CHU Lyon
CHU de Dijon
CHU de Brest
CHU Paris - Tenon
Hôpital Pitié-Salpêtrière

status_simplified: Completed


title: Prospective Analysis of Morbi-mortality of Patients With Cancers in Active Phase of Treatment Suspected or Diagnosed of a SARS-CoV-2 Infection

summary: National multicentre epidemiological study to describe retrospectively and prospectively the clinical outcomes of patients with a suspected coronavirus infection (either confirmed or not) while receiving a medical treatment for the underlying cancer

ReferenceCitation: Assaad S, Zrounba P, Cropet C; ONCOVID-19 study Consortium, Blay JY. Mortality of patients with solid and haematological cancers presenting with symptoms of COVID-19 with vs without detectable SARS-COV-2: a French nationwide prospective cohort study. Br J Cancer. 2021 Aug;125(5):658-671. doi: 10.1038/s41416-021-01452-4. Epub 2021 Jun 16.

lead_sponsor: Centre Leon Berard

location_facility: Institut de cancérologie Strasbourg Europe (ICANS)

location_facility: Institut Universitaire du Cancer de Toulouse - IUCT Oncopole

location_facility: Groupement Hospitalier Porte de Provence


title: Impact of Prone Position in Patients Under Spontaneous Breathing on Intubation or Non-invasive Ventilation or Death Incidence During COVID-19 Acute Respiratory Distress

summary:
The SARS-Cov2 viral pandemic is responsible for a new infectious disease called COVID-19 (CoronaVIrus Disease), is a major health problem. Respiratory complications occur in 15 to 40%, the most serious is acute respiratory distress syndrome (ARDS).

The management of COVID-19 is essentially symptomatic with respiratory oxygen supplementation in mild forms to invasive mechanical ventilation in the most severe forms.

Prone position (PP) reduced mortality in patients with ARDS in intensive care. Ding et al showed that PP and high flow oxygenation reduced the intubation in patients with moderate to severe ARDS.

The investigators hypothesize that the use of PP in spontaneously ventilation patients under oxygen standard could decrease incidence of intubation or non-invasive ventilation or death compared to conventional positioning management in medical departments.

status: Recruiting

study_type: Interventional

design_allocation: Randomized

primary_purpose: Supportive Care

ReferenceType: background

ReferenceCitation: Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill Patients With COVID-19. JAMA. 2020 Apr 21;323(15):1499-1500. doi: 10.1001/jama.2020.3633.

ReferenceCitation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:.

ReferenceCitation: Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.

ReferenceCitation: Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum in: JAMA Intern Med. 2020 Jul 1;180(7):1031.

ReferenceCitation: Nay MA, Planquette B, Perrin C, Clément J, Plantier L, Sève A, Druelle S, Morrier M, Lainé JB, Colombain L, Corvaisier G, Bizien N, Pouget-Abadie X, Bigot A, Bernard L, Nyamankolly E, Fossat G, Boulain T. Does awake prone positioning prevent the use of mechanical respiratory support or death in COVID-19 patients on standard oxygen therapy hospitalised in general wards? A multicentre randomised controlled trial: the PROVID-19 protocol. BMJ Open. 2022 Jul 8;12(7):e060320. doi: 10.1136/bmjopen-2021-060320.

lead_sponsor: Centre Hospitalier Régional d'Orléans

location_country: France Monaco

location_facility: CH de PERPIGNAN - Service Maladies infectieuses

location_facility: Centre Hospitalier Intercommunal de Cornouaille - Quimper Concarneau

location_facility: CHRU DE TOURS - Service Médecine interne et maladies infectieuses

location_facility: CHR d'Orleans - Service Maladies Infectieuses

location_facility: CHRU de Tours - Service Médecine interne et immunologie Clinique

location_facility: HOPITAL LARIBOISIERE - Service diabétologie, endocrinologie, nutrition

intervention_type: Other

status_simplified: Ongoing


type: Other Identifier

title: Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome

summary:
Acute Respiratory Distress Syndrome (ARDS) induces high mortality, particularly in the context of COVID-19 disease. Preliminary data from patients with ARDS related to COVID-19 disease appear to show significant effectiveness of prone positioning in intubated patients in terms of oxygenation as well as nasal high flow therapy before intubation. It should be noted that in Jiangsu province, secondarily affected, nasal high flow combined with the prone position was successfully integrated into care protocols.

The investigators hypothesize that the combined application of nasal high flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for tracheal intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

Investigators hypothesize that the combined application of nasal high-flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

primary_purpose: Treatment

ReferenceCitation: Ehrmann S, Li J, Ibarra-Estrada M, Perez Y, Pavlov I, McNicholas B, Roca O, Mirza S, Vines D, Garcia-Salcido R, Aguirre-Avalos G, Trump MW, Nay MA, Dellamonica J, Nseir S, Mogri I, Cosgrave D, Jayaraman D, Masclans JR, Laffey JG, Tavernier E; Awake Prone Positioning Meta-Trial Group. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med. 2021 Dec;9(12):1387-1395. doi: 10.1016/S2213-2600(21)00356-8. Epub 2021 Aug 20.

ReferenceCitation: Tavernier E, McNicholas B, Pavlov I, Roca O, Perez Y, Laffey J, Mirza S, Cosgrave D, Vines D, Frat JP, Ehrmann S, Li J. Awake prone positioning of hypoxaemic patients with COVID-19: protocol for a randomised controlled open-label superiority meta-trial. BMJ Open. 2020 Nov 11;10(11):e041520. doi: 10.1136/bmjopen-2020-041520.

ipd_sharing: Yes

ipd_sharing_description: Individual participant data after de-identification can be obtained by contacting the corresponding author.

lead_sponsor: University Hospital, Tours

location_facility: Surgical Intensive Care Unit, University Hospital, Tours

location_facility: Medical Intensive Care Unit, University Hospital, Amiens

location_facility: Medical Intensive Care Unit, Hospital, Orléans

location_facility: Intensive Care Unit, University Hospital, Lille

location_facility: Medical Intensive Care Unit, University Hospital, Dijon

location_facility: Medical Intensive Care Unit, University Hospital, Caen

location_facility: Medical Intensive Care Unit, University Hospital, Nantes

location_facility: Medical Intensive Care Unit, University Hospital, Nancy

location_facility: Medical Intensive Care Unit, Hospital, Béthune

location_facility: Intensive Care Unit, Hospital, Argenteuil

location_facility: Medical Intensive Care Unit, University Hospital, Nice

location_facility: Medical Intensive Care Unit, University Hospital, Poitiers

location_facility: Medical Intensive Care Unit, University Hospital, Tours

location_facility: Medical Intensive Care Unit, University Hospital, Brest

location_facility: Medical Intensive Care Unit, University Hospital, Grenoble

location_facility: Intensive Care Unit, Hospital, La Roche-sur-Yon

location_facility: Intensive Care Unit, University Hospital, Aix


type: EudraCT Number

title: Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy, a Multicenter Prospective Randomized Double-blind Placebo-controlled Trial.

acronym: CHASAP

summary: A randomized clinical trial to assess the efficiency of acetylsalicylic acid (aspirin) 150 mg/day started before 20 weeks of gestation in the prevention on maternal and fœtal complications in pregnant women with chronic hypertension.

ipd_sharing: No

lead_sponsor: Centre Hospitalier Intercommunal Creteil

location_facility: Centre Hospitalier Intercommunal de Créteil

intervention_type: Drug


title: A National, Multicenter, Randomized Controlled Trial to Assess the Efficacy of a Physical Activity Program to Improve Quality of Life and Reduce Fatigue in Women With Metastatic Breast Cancer

summary:
INTRODUCTION: Patients with a metastatic breast cancer suffer from a deteriorated quality of life and numerous symptoms such as pain, severe fatigue and a decrease of their physical fitness. As the feasibility of a physical activity program has been demonstrated in this population, ABLE02 aims to assess the efficacy of a 6 month-physical activity program based on connected devices to improve health-related quality of life and to reduce fatigue in women with metastatic breast cancer.

METHODS/ANALYSIS: ABLE02 is a prospective, multicenter, randomized, controlled and, open-label study. 244 patients with a metastatic breast cancer , at least one positive hormone receptor and a first-line chemotherapy planned will be randomly assigned (1:1 ratio) to: (i) the intervention arm to receive physical activity recommendations, an activity tracker to wear 24 hours a day during the whole intervention (6 months) with at least three walking sessions weekly and quizzes to answer each week on physical activity and nutrition (ii) the control arm to receive physical activity recommendations only. Assessments will be conducted at baseline, M3, M6, M12 and M18 to evaluate the clinical, physical, biological and psychological parameters and survival of participants. All questionnaires will be completed on a dedicated application.

DISCUSSION: An activity program based on smartphone application linked to an activity tracker may help to improve quality of life and reduce fatigue of patients with a metastatic breast cancer. The growth of e-health offers the opportunity to get real-time data as well as improving patient empowerment in order to change long-term behaviors.

ReferenceCitation: Delrieu L, Anota A, Trédan O, Freyssenet D, Maire A, Canada B, Fournier B, Febvey-Combes O, Pilleul F, Bouhamama A, Caux C, Joly F, Fervers B, Pialoux V, Pérol D, Pérol O. Design and methods of a national, multicenter, randomized and controlled trial to assess the efficacy of a physical activity program to improve health-related quality of life and reduce fatigue in women with metastatic breast cancer: ABLE02 trial. BMC Cancer. 2020 Jul 3;20(1):622. doi: 10.1186/s12885-020-07093-9.

location_facility: Institut de Cancérologie Lucien Neuwirth (ICLN)

location_facility: Institut de Cancérologie de l'Ouest (ICO)

intervention_type: Device


acronym: ICAR

title: Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

lead_sponsor: Centre Hospitalier St Anne

source: euctr

ReferenceCitation: Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. Erratum in: Lancet Respir Med. 2020 Feb 25;:.

ReferenceCitation: Chaigne B, Mouthon L. Mechanisms of action of intravenous immunoglobulin. Transfus Apher Sci. 2017 Feb;56(1):45-49. doi: 10.1016/j.transci.2016.12.017. Epub 2016 Dec 30. Review.

ReferenceCitation: Arish N, Eldor R, Fellig Y, Bogot N, Laxer U, Izhar U, Rokach A. Lymphocytic interstitial pneumonia associated with common variable immunodeficiency resolved with intravenous immunoglobulins. Thorax. 2006 Dec;61(12):1096-7.

ReferenceCitation: Oates-Whitehead RM, Baumer JH, Haines L, Love S, Maconochie IK, Gupta A, Roman K, Dua JS, Flynn I. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003;(4):CD004000. Review.

ReferenceCitation: Alejandria MM, Lansang MA, Dans LF, Mantaring JB 3rd. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013 Sep 16;(9):CD001090. doi: 10.1002/14651858.CD001090.pub2. Review.

ReferenceCitation: Mazeraud A, Jamme M, Mancusi RL, Latroche C, Megarbane B, Siami S, Zarka J, Moneger G, Santoli F, Argaud L, Chillet P, Muller G, Bruel C, Asfar P, Beloncle F, Reignier J, Vinsonneau C, Schimpf C, Amour J, Goulenok C, Lemaitre C, Rohaut B, Mateu P, De Rudnicki S, Mourvillier B, Declercq PL, Schwebel C, Stoclin A, Garnier M, Madeux B, Gaudry S, Bailly K, Lamer C, Aegerter P, Rieu C, Sylla K, Lucas B, Sharshar T. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Feb;10(2):158-166. doi: 10.1016/S2213-2600(21)00440-9. Epub 2021 Nov 11.

ReferenceCitation: Mazeraud A, Gonçalves B, Aegerter P, Mancusi L, Rieu C, Bozza F, Sylla K, Siami S, Sharshar T. Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial. Trials. 2021 Feb 28;22(1):170. doi: 10.1186/s13063-021-05118-7.

location_facility: Grand hopital de l'est Francilien - site de Jossigny

location_facility: Hôpital de la Croix Rousse Novembre 2019

location_facility: Service de Médecine Intensive-Réanimation, CHU

location_facility: CHU Pitié Salpétriere Service de réanimation chirurgicale

location_facility: Service de réanimation polyvalente, rond point de Girac

location_facility: Pôle de Médecine intensive/réanimation Hôpital Salengro, CHRU de Lille

summary: As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.


title: MAZEPPA: Phase II PRODIGE-GERCOR Study to Evaluate MAintenance Therapy With Olaparib or Selumetinib Plus Durvalumab According to BRCAness and KRAS Somatic Status Personalized in Metastatic Pancreatic Adenocarcinoma Patients

summary:
MAZEPPA is open-label, phase II study to assess the efficacy of a genomic-driven maintenance therapy in terms of PFS in Pancreatic ductal adenocarcinoma (PDAC) patients with disease controlled after 4 months of mFOLFIRINOX chemotherapy as following:

Patients with a BRCAness somatic profile: olaparib Arm A. Patients with no BRCAness profile and with KRAS mutation randomization between durvalumab plus selumetinib Arm B, versus FOLFIRI Arm C.

lead_sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group

location_facility:
centre Léon Bérard
CHU Robert Debré
Centre Georges François Leclerc
Centre Paul Strauss
Hôpital Nord Franche Comté
Hôpital Privé Jean Mermoz
GH Diaconesses Croix Saint Simon
Centre François Baclesse
Institut Mutualiste Montsouris
CHRU Jean Minjoz
CHU Grenoble Alpes Hôpital Michallon
GHPSO Site de Creil
Hôpital Pitié Salpêtrière
Hôpital Beaujon
Polyclinique Bordeaux Nord Aquitaine
CHRU Lille
ICO Site de Saint Herblain
Hôpital Saint Antoine
Hôpital Saint Joseph Saint Luc
Institut Paoli Calmette
Hôpital Franco-Britannique
Hôpital Européen
CHU Poitiers
Hôpital Européen Georges Pompidou
CHU Toulouse IUCT Rangueil
Institut Sainte Catherine
CHU La Timone
Hôpital Trousseau
CHU Dijon

lead_sponsor_type: industriel


title: Prospective Descriptive Study on the Evolution of Pulmonary Ultrasound in Patients Hospitalized for Covid19

summary:
Clinical thoracic ultrasound plays an important role in the exploration, diagnosis and follow-up of thoracic pathologies.

The COVID (Coronavirus Disease) epidemic is leading to a large influx of patients in the emergency department with respiratory disorders. The rapid diagnosis of respiratory disorders in infected patients is important for further management.

Chest ultrasound has already demonstrated its value in the diagnosis of pneumonia in the emergency department with superiority over chest X-ray.

However, there is little data on the thoracic ultrasound semiology of viral pneumonia in general and of COVID in particular.


title: French Register Of Patients With Hemopathy Eligible For CAR-T Cell Treatment (DESCAR-T)

summary: This study is a registry including prospective and retrospective data on all patients who have been presented in a Multidisciplinary tumor board or RCP to be eligible for CAR-T cell treatment.

ReferenceCitation: Bachy E, Le Gouill S, Di Blasi R, Sesques P, Manson G, Cartron G, Beauvais D, Roulin L, Gros FX, Rubio MT, Bories P, Bay JO, Llorente CC, Choquet S, Casasnovas RO, Mohty M, Guidez S, Joris M, Loschi M, Carras S, Abraham J, Chauchet A, Drieu La Rochelle L, Deau-Fischer B, Hermine O, Gastinne T, Tudesq JJ, Gat E, Broussais F, Thieblemont C, Houot R, Morschhauser F. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022 Oct;28(10):2145-2154. doi: 10.1038/s41591-022-01969-y. Epub 2022 Sep 22.

lead_sponsor: The Lymphoma Academic Research Organisation

location_facility: Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)

location_facility: APHP - Hôpital Universitaire Robert Debré

location_facility: Institut d'Hématologie et d'Oncologie Pédiatrique (IHOP)

location_facility: Institut de Cancérologie Hématologie Universitaire de Saint Etienne

location_facility: Hôpital de la Milétrie - CHU de Poitiers

location_facility: ICANS (Institut de Cancérologie Strasbourg Europe)

location_facility: Institut d'Hématologie de Basse Normandie


status: Terminated

acronym: HYCOVID

title: Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study

lead_sponsor: University Hospital, Angers

ReferenceCitation: Dubée V, Roy PM, Vielle B, Parot-Schinkel E, Blanchet O, Darsonval A, Lefeuvre C, Abbara C, Boucher S, Devaud E, Robineau O, Rispal P, Guimard T, d'Anglejean E, Diamantis S, Custaud MA, Pellier I, Mercat A; HYCOVID study group; HYCOVID investigators; Angers University Hospital; Cholet Hospital; Laval Hospital; Le Mans Hospital; Tours University Hospital; Quimper Hospital; La Roche sur Yon Hospital; Tourcoing Hospital; Orléans Hospital; Nantes University Hospital; Niort Hospital; Lorient Hospital; Brest University Hospital; Cherbourg Hospital; Saint-Brieuc Hospital; Créteil - APHP University Hospital; Saint-Antoine - APHP University Hospital; Saint-Etienne University Hospital; Toulouse University Hospital; Melun Hospital; Dijon University Hospital; Princesse Grace - Monaco Hospital; Versailles Hospital; Colmar Hospital; Agen-Nerac Hospital; Caen University Hospital; Saint-Nazaire Hospital; Nantes - Confluent Hospital; Limoges University Hospital; Poitiers University Hospital; Amiens University Hospital; Bobigny - APHP University Hospital; Cergy-Pontoise Hospital; Valencienne Hospital; Valencienne - Clinique Tessier Hospital; Henri-Mondor - APHP University Hospital; Chalon-sur-Saône Hospital; Marseille European Hospital; Auxerre Hospital; Diaconnesses Croix-Saint-Simon Hospital; Marseille - Saint Joseph Hospital; HYCOVID management team: Steering committee (authors); HYCOVID management team: Independant data safety and monitoring board; HYCOVID management team: Independent adjudication of clinical events committee; Study management: Coordination; Study management: Data management. Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial. Clin Microbiol Infect. 2021 Aug;27(8):1124-1130. doi: 10.1016/j.cmi.2021.03.005. Epub 2021 Apr 1.

location_facility:
CH Valenciennes
CH Cholet
CH Agen
APHP Saint-Antoine
CHU Angers
CHU Toulouse
CH Lorient
CH Princesse Grace
CH Quimper
APHP Avicenne
CH Cherbroug
APHP Joffre Dupuytren
La Pitié-Salpétrière
APHP Henri Mondor
Hôpital Privé du Confluent
Hôpital Européen - Marseille
CH Tourcoing
CH Laval
CHU Tours
CHR Orléans
CHU Poitiers
GH Croix Saint Simon
CH Melun
CH Vannes
CH Niort
CHD Vendée
CH Compiègne
CH Saint-Nazaire
CH Emile Roux
CHU Nantes
Clinique Tessier Valenciennes
CHU Saint-Etienne
CH Saint-Brieuc
CHU Caen
Hôpital Saint-Joseph
CH Versailles
CHU Brest
CH Le Mans
CHU Limoges
CH Auxerre
APHP Emile ROUX
CH Chalon Sur Saône
CH Intercommunal Créteil
CHU Amiens
CH Pointoise
CHU Dijon
CH Colmar

summary:
A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated.

Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening.

The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.


title: Interest of Peri Operative CHemotherapy In Patients With CINSARC High-risk Localized Soft Tissue Sarcoma

summary:
Phase III, multicenter, randomized open-label and comparative study designed to demonstrate whether adding 4 cycles of peri-operative doxorubicin-based chemotherapy improves metastasis-free survival as compared with standard management in patients with resectable STS, considered as high-risk according to CINSARC (Complexity Index in SARComas) signature.

After signed informed consent, patients considered as eligible to CHIC-STS study by the investigator will be enrolled in the study and a molecular screening will be performed (600 patients will be screened).

Patients considered as low-risk according to CINSARC signature will be treated at the discretion of the clinicians (prospective cohort).

Patients considered as high-risk according to CINSARC signature will be randomized in the open-label multicenter phase III trial and assigned in one of the two following treatments arms:

Arm A (control arm): Standard of care (surgical excision +/- external radiotherapy).
Arm B (experimental arm): Standard of care + 4 cycles of intravenous chemotherapy during 12 weeks.

A total of 250 patients will have to be randomized with 125 patients in each arm.

ReferenceCitation: Filleron T, Le Guellec S, Chevreau C, Cabarrou B, Lesluyes T, Lodin S, Massoubre A, Mounier M, Poublanc M, Chibon F, Valentin T. Value of peri-operative chemotherapy in patients with CINSARC high-risk localized grade 1 or 2 soft tissue sarcoma: study protocol of the target selection phase III CHIC-STS trial. BMC Cancer. 2020 Jul 31;20(1):716. doi: 10.1186/s12885-020-07207-3.

lead_sponsor: Institut Claudius Regaud

location_facility: Institut de Cancérologie de Lorraine - Centre Alexis Vautrin

location_facility: Institut de Cancérologie Strasbourg Europe

location_facility: Institut Universitaire du Cancer Toulouse Oncopole


title: EVALUATION OF HIGH INTENSITY FOCUSED ULTRASOUND (HIFU) IN CURATIVE TREATMENT OF LOCALIZED PROSTATE CANCER AT LOW OR INTERMEDIATE RISK AND IN TREATMENT OF RECURRENCE AFTER RADIOTHERAPY (FORFAIT INNOVATION ART L165-1-1 Social Security Code)

acronym: HIFI

summary:
to compare the efficacy of HIFU treatment with standard treatment in two situations:

as first-line cancer treatment, HIFU is compared to radical prostatectomy.
for patients with recurrence after external beam radiotherapy, HIFU treatment is compared to radical prostatectomy.

design_allocation: Non-Randomized

lead_sponsor: Association Francaise d'Urologie

location_country: France Guadeloupe

location_facility: Fondation St Jean de Dieu - Clinique Oudinot

intervention_type: Procedure


title: Multicentric Phase III Trial Comparing Two Strategies in Intermediate-risk Differentiated Thyroid Cancer Patients: Systematic Radioiodine Administration Versus Decision of Radioiodine Treatment Guided by a Post-operative Work-up Based on Serum Tg Values and Diagnostic RAI Scintigraphy

acronym: INTERMEDIATE

summary: This trial is comparing two strategies in intermediate-risk differentiated thyroid cancer patients: Systematic radioiodine administration versus decision of radioiodine treatment guided by a post-operative work-up based on serum Tg values and diagnostic RAI scintigraphy

lead_sponsor: Centre Francois Baclesse

location_facility: Institu de Cancérologie de l'Ouest - Site St Herblain

location_facility: Institu de Cancérologie de l'Ouest - Site Angers


status: Active, not recruiting

acronym: SWIFT

title: A One-year, Single-arm, Open-label, Multicenter Study Assessing the Effect of Brolucizumab on Disease Control in Adult Patients With Suboptimal Anatomically Controlled Neovascular Age-related Macular Degeneration (SWIFT)

lead_sponsor: Novartis Pharmaceuticals

ipd_sharing_description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

summary:
Neovascular age-related macular degeneration is characterized by the presence of choroidal neovascularization (CNV), which consists of abnormal blood vessels originating from the choroid that can lead to hemorrhage, fluid exudation, and fibrosis, resulting in photoreceptor damage and vision loss.

The safety and efficacy of brolucizumab were assessed in 2 randomized, multicenter, double-masked, active treatment-controlled Phase 3 studies in nAMD patients (the HAWK study (RTH258-C001 [NCT02307682]) and the HARRIER study (RTH258-C002 [NCT02434328]). Accordingly, a new Phase 3b study (TALON, CRTH258A2303) is being conducted to evaluate the efficacy and safety of brolucizumab in a Treat-to-Control (TtC) regimen for the treatment of naïve patients with nAMD. In this TtC regimen, patients receive 3 consecutive injections every 4 weeks and then the injection interval is extended by 4 weeks up to a maximum of a 16-week interval. The decision to extend or reduce the injection interval is taken by the Investigator at each visit based on his/her judgment of disease activity, according to the patient visual and/or anatomic outcomes. If there is no disease activity, the injection interval can be extended by 4 weeks ; if disease activity occurs or recurs, the injection interval should be shortened accordingly by 4 weeks at a time or to a minimal interval of 8 weeks. The injection interval can also be maintained if the Investigator deems that the patient do not benefit from injection interval adjustment.

Since all these studies were conducted in a naïve nAMD patient population, no data are available on the efficacy and safety of brolucizumab in pretreated nAMD patients who still present active exudation.


title: Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study

acronym: POCHI

summary:
About 85% of cases of non-metastatic colorectal cancer (CRC) are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR); which are also called CRC with microsatellite stability (MSS). Other CRC, i.e. 15%, are "microsatellite unstable" (MSI) with deficient DNA Mismatch-Repair system (dMMR). These latter are characterised by generation of many neo-antigens, which result in a high anti-tumour immune response and a high peri- and/or intra-tumour lymphocyte infiltration (TIL). Investigators recently showed, with a prospectively validated immune score, that 14% of localised MSS/pMMR CRC are also highly infiltrated by CD3+ lymphocytes. This same immune score has made it possible to measure high lymphocyte infiltration in hepatic metastases, in particular, in patients treated with XELOX/FOLFOX.

Pembrolizumab, an anti-PD1 monoclonal antibody (programmed death-1) is an immune checkpoint inhibitor (ICI) of PD1/PD-L1 axis, recently approved in many cancers. Anti-PD1 antibodies have recently been reported as being very effective in patients with dMMR metastatic CRC (mCRC). In the study by Le DT et al. pMMR mCRC did not seem to benefit from anti-PD1 antibodies. However, it is possible that 20% of pMMR mCRC with a high CD3+ infiltrate in the tumour may be a subgroup of pMMR mCRC sensitive to ICI, as is the case for dMMR mCRC. Lastly, immunogenic cell death induced by chemotherapy, such as oxaliplatin, can increase the efficacy of ICI.

The prognostic value of lymphocyte infiltrate has been demonstrated in CRC by several teams. However, no validated test is used in routine clinical practice. Previously, investigators described an automated and reproducible method for analysis of TIL and investigators validated it for clinical use. Automated tests evaluating TIL are performed on virtual slides and have showed that, out of 1,220 tumours tested, 20% were highly infiltrated by CD3+ T cells. Patients presenting with a pMMR CRC with a high immune infiltrate had a better progression-free survival (HR=0.70; p=0.02). An immunoscore® described by Galon et al. has also a high prognostic value in CRC and is based on CD3+ and CD8+ T cells infiltration in the center and periphery of the tumour. Finally, approximately 14% of tumours with a high immune infiltrate have been found in patients with metastatic CRC.

Investigators formulated the hypothesis that patients with a pMMR CRC with a high immune infiltrate can be sensitive to ICI . Therefore, blocks of resected primary tumour will be collected and analysed prospectively. For each patient, slides containing tumour tissue and adjacent non-tumour tissue will be analysed using two techniques : immunoscore® and TuLIS score.It consist in Immunohistochemistry with CD3 and CD8 staining. Slides will be scanned and analysed by image analysis as previously described . Tumours will then be classified as having a "high" or "low" immune response according to type of lymphocyte infiltrate, which is independent of pre-analytic conditions. Only patients with a high immune response will be eligible for the POCHI trial. Other biomarkers will be analysed like other immune populations or mutational load. If investigators identify an immune score which seems clinically relevant to predict sensitivity to ICI in pMMR mCRC, this will make it possible to plan a randomised phase III trial comparing chemotherapy and anti-angiogenic antibody versus chemotherapy and anti-angiogenic antibody plus pembrolizumab in patients with a pMMR mCRC with a high immune score and/or a hypermutated genotype.

Investigators choose PFS at 10 months as primary endpoint in POCHI trial because it is a surrogate marker of OS. Actually median PFS in first-line setting with a doublet plus a biological agent is range from 8 to 11 months in unresectable mCRC, corresponding to a PFS of 50% at 10 months. The alternative clinical hypothesis to obtain 70% of patients alive and without progression at 10 months is ambitious and currently not achieved with current chemotherapies plus a biological agent. Up until now there is no data concerning survivals outcomes of patients with a MSS mCRC with high immune infiltration score.

ReferenceCitation: Carbonnel F, Soularue E, Coutzac C, Chaput N, Mateus C, Lepage P, Robert C. Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora? Semin Immunopathol. 2017 Apr;39(3):327-331. doi: 10.1007/s00281-016-0613-x. Epub 2017 Jan 16. Review.

ReferenceCitation: Caulet M, Lecomte T, Bouché O, Rollin J, Gouilleux-Gruart V, Azzopardi N, Léger J, Borg C, Douillard JY, Manfredi S, Smith D, Capitain O, Ferru A, Moussata D, Terrebone E, Paintaud G, Ternant D. Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients. Clin Pharmacokinet. 2016 Nov;55(11):1381-1394.

ReferenceCitation: Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012 Jun 28;486(7404):537-40. doi: 10.1038/nature11219.

ReferenceCitation: Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012 Mar 15;12(4):298-306. doi: 10.1038/nrc3245. Review.

ReferenceCitation: Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.

ReferenceCitation: Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001 Feb 1;19(3):843-50.

ReferenceCitation: Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.

ReferenceCitation: Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D'Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017 May 4;545(7652):60-65. doi: 10.1038/nature22079. Epub 2017 Apr 10.

ReferenceCitation: Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, Konieczny BT, Daugherty CZ, Koenig L, Yu K, Sica GL, Sharpe AH, Freeman GJ, Blazar BR, Turka LA, Owonikoko TK, Pillai RN, Ramalingam SS, Araki K, Ahmed R. Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science. 2017 Mar 31;355(6332):1423-1427. doi: 10.1126/science.aaf0683. Epub 2017 Mar 9.

ReferenceCitation: Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016 Jun;22(6):598-605. doi: 10.1038/nm.4102. Epub 2016 May 9.

ReferenceCitation: Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, Chen CT, Veronese S, Zanon C, Sartore-Bianchi A, Gambacorta M, Gallicchio M, Vakiani E, Boscaro V, Medico E, Weiser M, Siena S, Di Nicolantonio F, Solit D, Bardelli A. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012 Jun 28;486(7404):532-6. doi: 10.1038/nature11156.

ReferenceCitation: Pauken KE, Wherry EJ. Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 2015 Apr;36(4):265-76. doi: 10.1016/j.it.2015.02.008. Epub 2015 Mar 18. Review.

ReferenceCitation: Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. doi: 10.1038/nature08821.

ReferenceCitation: Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan 5;359(6371):91-97. doi: 10.1126/science.aan3706. Epub 2017 Nov 2.

ReferenceCitation: Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011 Jun;11(6):426-37. doi: 10.1038/nrc3066. Epub 2011 May 12. Review.

ReferenceCitation: Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I, Cosnes J, Seksik P, Langella P, Skurnik D, Richard ML, Beaugerie L. Fungal microbiota dysbiosis in IBD. Gut. 2017 Jun;66(6):1039-1048. doi: 10.1136/gutjnl-2015-310746. Epub 2016 Feb 3.

ReferenceCitation: Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta. 2001 Nov;313(1-2):139-42.

ReferenceCitation: Thierry AR, Mouliere F, El Messaoudi S, Mollevi C, Lopez-Crapez E, Rolet F, Gillet B, Gongora C, Dechelotte P, Robert B, Del Rio M, Lamy PJ, Bibeau F, Nouaille M, Loriot V, Jarrousse AS, Molina F, Mathonnet M, Pezet D, Ychou M. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med. 2014 Apr;20(4):430-5. doi: 10.1038/nm.3511. Epub 2014 Mar 23.

ReferenceCitation: Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014 Nov 27;515(7528):568-71. doi: 10.1038/nature13954.

ReferenceCitation: Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Bérard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Doré J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013 Nov 22;342(6161):971-6. doi: 10.1126/science.1240537.

ReferenceCitation: Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013 Mar 29;339(6127):1546-58. doi: 10.1126/science.1235122. Review.

lead_sponsor: Federation Francophone de Cancerologie Digestive

location_facility: Privé - Cac - Paul Strauss / Institut de Cancérologie de Strasbourg Europe

location_facility: CH - GROUPE HOSPITALIER DE La Rochelle RE AUNIS

location_facility: Chu - Hôpital Morvan - Institut de Cancérologie

location_facility: Privé - Groupe Hospitalier Diaconesses Croix Saint Simon

location_facility: Ch - Centre Hospitalier de La Côte Basque

location_facility: Ch - Ghi - Groupe Hospitalier de L'Est Francilien - Site de Meaux

location_facility: Chu - Hôpital Ambroise Paré - Service Anatomie Pathologique

location_facility: Chu - Centre Hospitalier Universitaire de Saint Etienne - Hôpital Nord - Service Hge

location_facility: Privé - Polyclinique de Blois - 3Eme Etage

location_facility: Chu - Centre Hospitalier Universitaire Pontchaillou

location_facility: Privé - Cac - Institut de Cancerologie de Lorraine

location_facility: Privé - Cac - Ico - Site René Gauducheau

location_facility: Privé - Cac - Centre Georges-Francois Leclerc

location_facility: Chu - Centre Hospitalier Universitaire Robert Debre

location_facility: Prive - Institut Du Cancer Avignon Provence

location_facility: Chu - Centre Hospitalier Universitaire de Poitiers - La Miletrie


title: Sevoflurane for Sedation in Acute Respiratory Distress Syndrome: A Multicenter Prospective Randomized Trial

acronym: SESAR

summary:
This study evaluates whether a sedation with inhaled sevoflurane will decrease mortality and increase time off the ventilator at 28 days in patients with acute respiratory distress syndrome (ARDS).

Half of the patients will receive inhaled sedation with sevoflurane and the other half will receive intravenous sedation with propofol.

lead_sponsor: University Hospital, Clermont-Ferrand

location_facility: Hautepierre Hospital, University Hospitals

location_facility: Saint-Louis University Hospital - Assistance Publique-Hôpitaux

location_facility: Hotel Dieu Hospital - University Hospital

location_facility: Cavale Blanche Hospital - University Hospital

location_facility: Lapeyronie Hospital - University Hospital

location_facility: Pitié-Salpêtrière Hospital, - Assistance Publique-Hôpitaux

location_facility: Pasteur 2 Hospital - University Hospital

location_facility: Timone Hospital - Assistance Publique-Hôpitaux

location_facility: Saint-Antoine University Hospital - Assistance Publique-Hôpitaux

location_facility: Saint-Eloi Hospital - University Hospital


type: Other Grant/Funding Number

title: Eosinophil-driven Corticotherapy for Patients Hospitalized for COPD Exacerbation: a Double-blind, Randomized, Controlled Trial

acronym: eo-Drive

summary:
The primary objective of this study is to compare treatment failure rates between a group of eosinophilic (eosinophilia > 2% on day 1 of hospitalization) patients hospitalised for a COPD exacerbation treated via corticotherapy versus a similar group treated via placebo.

Secondarily, treatment failure rates will also be compared between a group of non-eosinophilic patients hospitalised for a COPD exacerbation treated via corticotherapy versus a similar group treated via placebo. Study arms will also be compared for additional aspects of efficacy and safety:

speed of recovery during the initial hospitalization;
corticosteroid side effects / induced comorbidities;
changes in symptoms and episodes of exacerbation;
pulmonary function, oxygen use and ventilation;
patient trajectories and resource use (e.g. survival, consults, episodes of hospitalization, medications);
drug consumption (especially as relates to COPD management, exacerbations and induced comorbidities);
health status, quality of life, activity/disability;
patient safety / adverse events in general.

Eosinophilia thresholds optimizing the prediction of corticosteroid response and COPD outcomes will be re-evaluated. The relationships between corticosteroid response and key biomarkers (e.g. infectious groups) will be thoroughly explored, including within eosinophil strata. Potential gender subgroups differences will also be evaluated.

Finally, in prevision of further exploratory studies, a biological collection and an imaging library will be created in association with this protocol. The biological collection will be used to explore the genetic basis and physiology linked with treatment response, gender and patient trajectories. The image library will be used as a platform for the exploration of new imaging markers developed, for example, via machine learning and affiliated techniques.

ReferenceCitation: Suehs CM, Zysman M, Chenivesse C, Burgel PR, Couturaud F, Deslee G, Berger P, Raherison C, Devouassoux G, Brousse C, Roche N, Molimard M, Chinet T, Devillier P, Chanez P, Kessler R, Didier A, Martinat Y, Le Rouzic O, Bourdin A. Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study. BMJ Open. 2020 Jul 1;10(7):e035811. doi: 10.1136/bmjopen-2019-035811.

ipd_sharing_description:
The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study. Data (and an accompanying data dictionary) will be de-identified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity.

Data will be made available to persons who address a reasonable dataset request to the sponsor coordinating team (c/o Dr Carey Suehs, Department of Medical Information, Hôpital La Colombière, 39 avenue Charles Flahault, 34295 Montpellier Cedex 5, France).

In accordance with French law, dataset usage requests must by approved by the French CNIL (Commission Nationale de l'Informatique et des Libertés : https://www.cnil.fr/professionnel) prior to access.

lead_sponsor: University Hospital, Montpellier

location_facility: Centre hospitalier intercommunal de Créteil

location_facility: APHP - Hôpital Universitaire Pitié-Salpétrière

location_facility: APHP - Hopital Européen Georges Pompidou


title: A Phase II, Multi-centre Study, to Evaluate the Efficacy and Safety of Osimertinib Treatment for Patients With EGFR-mutated Non-small Cell Lung Cancer (NSCLC) With Brain or Leptomeningeal Metastases

acronym: ORBITAL

summary:
Treatment of non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutation is mainly based on tyrosine kinase inhibitors (TKIs) targeting EGFR. 1st or 2nd generation inhibitors have been shown to be superior to chemotherapy in terms of Progression-Free Survival (PFS) when used as 1st line treatment.

In case of progression at several metastatic sites, systemic treatment will be considered and will depend on the presence of the TKI resistance mutation, the T790M mutation. In the presence of the T790M mutation, osimertinib is superior to chemotherapy in terms of progression-free survival, while in the absence of the T790M mutation, platinum salt chemotherapy is recommended. In case of local progression, treatment of the site in progression by radiotherapy and/or surgery is considered. As these local treatments can cause long-term adverse effects, systemic treatments are increasingly being considered in this indication.

Brain and leptomeningeal metastases are the most frequent isolated site of progression in EGFR mutated patients treated with TKI. The high frequency of isolated cerebral and leptomeningeal progression is a consequence of the lower diffusion of 1st and 2nd generation TKIs in the central nervous system (CNS). Osimertinib is a 3rd generation TKI that has the particularity of overcoming the T790M mutation and having greater brain penetration than 1st or 2nd generation TKIs, which could make it an attractive therapeutic option in the event of brain progression or leptomeningeal progression. However, its efficacy in patients with cerebral or leptomeningeal metastases is still poorly understood.

ipd_sharing: Undecided

lead_sponsor: Intergroupe Francophone de Cancerologie Thoracique

location_facility: Centre Hospitalier de Villefranche-sur-Saône

location_facility: Institut de Cancérologie de l'Ouest - René Gauducheau

location_facility: Centre Hospitalier Régional - Hôpital de la Source

location_facility: Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

location_facility: Lyon - URCOT Centre Hospitalier Universitaire

location_facility: Centre Hospitalier Intercommunal de Créteil


title: Study on the Dimethyl Fumarate (DMF, Tecfidera®) Persistence of Remitting-relapsing Multiple Sclerosis (RR-MS) Patients Included in the French Patient Support Program (PSP) OroSEP

acronym: TEC-ADHERE

summary:
The primary objective is to compare oral dimethyl fumarate (DMF) persistence at six months in relapsing-remitting multiple sclerosis (RR-MS) participants initiating DMF with and without OroSEP patient support program (PSP), respectively.

The secondary objectives are: to compare oral DMF persistence at one month and three months in RR-MS participants initiating DMF with and without OroSEP PSP, respectively; To compare oral DMF adherence at six months in RR-MS participants initiating DMF with and without OroSEP PSP; To compare at three months and six months the reason of oral DMF discontinuation, in the two groups; To describe the percentage of participants with treatment-related adverse events globally and by class of adverse events, in the two groups of participants; To assess the evolution of participants' anxiety globally and to compare it at inclusion and at six months in participants with and without OroSEP PSP, respectively; To describe participants' satisfaction regarding oral DMF initiation and follow-up globally at six months and to compare it in patients with and without OroSEP PSP, respectively;

For OroSEP PSP group: To assess participants' satisfaction regarding their participation in OroSEP PSP at six months; To assess neurologists' satisfaction regarding their participation in OroSEP PSP, after the last participant last visit of center.

ipd_sharing_description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

lead_sponsor: Biogen

location_facility:
Research site
Research Site


title: Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation With Stabilized Coronary Artery Disease

acronym: AQUATIC

summary:
Long-term aspirin (ASA) is the standard recommended antithrombotic therapy in patients with stable coronary artery disease (CAD), especially following stenting (Class I, Level A).
Long-term oral anticoagulation (OAC) is the standard antithrombotic therapy in patients with atrial fibrillation (AF) associated with one or more risk factor for stroke (Class I, Level A).
During the first year following acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), several studies evaluating the combination of OAC treatment and antiplatelet therapy are either already published or ongoing.
At distance of the index ACS and/or PCI, patients with stable CAD and concomitant AF remain at particular high-risk of ischemic (3 to 4 times higher as compared to patients with stable CAD without AF) and bleeding events. Antithrombotic management of these patients is subsequently highly challenging in clinical practice. The European task force suggests that the use of a full-dose anticoagulant monotherapy without any antiplatelet therapy should be the default strategy in such patients with both, AF and stable CAD.
However, evidences are sparse and weak to support such a strategy (only observational studies with many biases) and no randomized trial has assessed this question. These patients, especially those at high-risk of recurrent ischemic events (post- ACS, diabetes, multivessel CAD…) may benefit from the combination of OAC and aspirin at long-term. Indeed the crude event rate of ischemic events is much higher than the crude event rate of bleeding in this specific population. Ischemic events are 2 to 3 times more frequent than bleeding in daily practice.
The benefit/risk ratio of these two different strategies (ASA in combination with OAC vs. OAC alone) in patients at high-risk of recurrent coronary and vascular events remains unknown. Dual therapy with full-dose anticoagulation and ASA may lead to higher risk of major bleeding, while stopping ASA in stabilized high-risk patients after PCI may lead to poorer outcome regarding ischemic events.
The coordinating investigators therefore designed a double blind placebo controlled trial in order to assess the optimal antithrombotic regimen that should be pursued long-life in this subset of patients.

study_start_date_type: Anticipated

status: Not yet recruiting

lead_sponsor: University Hospital, Brest

location_facility: Centre Hospitalier René Dubos - Cergy Pontoise

location_facility: CH Louis Pasteur - Chartres - Le Coudray

location_facility: Hôpital Haut Lévêque -CHU Bordeaux-Pessac


title: A National Prospective Cohort for Pregnancies in Patients With Rare Vascular Anomalies: COGRare5 Study

summary:
There are no prospective studies of pregnancies for the diseases studied here in (Heredity Hemorrhagic Telangiectasia, Marfan syndrome, primary lower limb lymphedema, superficial arteriovenous malformations, and cerebro-spinal arteriovenous malformations) although complications of these can present life-threatening health problems for the mother and her baby.

The purpose of this National prospective study is to obtain greater insight into obstetrical complications associated with rare maternal vascular genetic disorders in order to improve prevention and to reduce risk of death.

In this context, experts and patient associations consider that there is a need to make real progress in the formulation of recommendations based on scientific data.

lead_sponsor: Hospices Civils de Lyon

location_facility: Service de Génétique Médicale, Hôpital de Hautepierre

location_facility: Service Médecine Interne - Médecine vasculaire - CHU de Rouen, Hôpital Charles Nicolle

location_facility: Centre de Référence pour la maladie de Rendu-Osler - Service Génétique Clinique - Hôpital Femme-Mère-Enfant - Hospices Civils de Lyon

location_facility: Service de Médecine interne et immunologie clinique + Service de Médecine Vasculaire - Hôpital Saint André, CHU de Bordeaux

location_facility: Unité de neuro-interventionnelle CHU Nice, Hôpital Pasteur 2

location_facility: Service Pneumologie + Service de Dermatologie _ Hôpital Bretonneau Centre Hospitalier Régional Universitaire de TOURS

location_facility: Service de Médecine Interne et Maladies Vasculaires + Service Neuropédiatrie et neurochirurgie de l'enfant - CHU Angers

location_facility: Service de Médecine Interne + Service Médecine Vasculaire _ Hôpital RANGUEIL

location_facility: Service Médecine Interne Estaing CHU de Clermont-Ferrand - Hôpital d'Estaing

location_facility: Unité de Génétique médicale, CHU de Rennes, Hôpital Sud

location_facility: Service de Lymphologie - Hôpital Cognacq-Jay - Paris

location_facility: Service d'imagerie médicale - Neuroradiologie interventionnelle - Hôpital Neurologique P. Wertheimer - HCL

location_facility: Service de neuroradiologie diagnostique et interventionnelle - CHU de Nancy, Hôpital St-Julien

location_facility: Service d'Imagerie Pédiatrique et Fœtale et Consultation Pluridisciplinaire des Angiomes - Hôpital Femme-Mère-Enfant - HCL

location_facility: Service de Médecine Vasculaire - Hôpital de la Côte de Nacre

location_facility: Service de Cardiologie - Hôpital Bichat, AP-HP

location_facility: Service Pneumologie et Oncologie Thoracique - AP-HP Hôpital Ambroise Paré

location_facility: Service Médecine interne - CHRU de Lille - Hôpital Claude Huriez

location_facility: Service de Cardiologie _ Hôpital des Enfants (Purpan)

location_facility: Service de Médecine vasculaire et HTA - Hôpital Albert Calmette, CHRU de Lille

location_facility: Service Médecine Interne - Hôpital Saint-Eloi, CHU de Montpellier

location_facility: Service de Pneumologie CHU de Rennes - Hôpital Pontchaillou

location_facility: Service de Neuroradiologie Interventionnelle - Hôpital Foch

location_facility: Service Radiologie-pneumologie interventionnelle - Hôpital Tenon AP-HP

location_facility: Service de Neuroradiologie - AP-HP - Paris (Hôpital Lariboisière)

location_facility: Clinique cardiologique et des maladies vasculaires CHU de Nantes, Hôpital G. R. LAENNEC

location_facility: Service de Médecine Vasculaire et Thérapeutique, Explorations Fonctionnelles Vasculaires - CHU de Saint-Etienne - Hôpital Nord

location_facility: Service de Neuroradiologie Interventionnelle - Fondation Adolphe de Rothschild

location_facility: CHU Dijon Bourgogne - Hôpital François Mitterrand


title: Evaluation of a Marine OXYgen Carrier for Organ Preservation : a Multicenter Randomized Study Evaluating the Efficacy of HEMO2life® Versus Standard of Care in Renal Transplantation

acronym: OXYOP 2

summary:
Preventing ischemia/reperfusion injuries (IRIs) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRIs is delayed graft function (DGF).

The medical device HEMO2life®, an oxygen carrier developed by the Hemarina French Company, is a natural extracellular hemoglobin (Hb) isolated from the marine lugworm Arenicola marina. This biopolymer of high molecular weight (~3,600 kDa) has a large oxygen binding capacity, carrying up to 156 oxygen molecules when saturated (4 for human Hb). It releases oxygen according to a simple gradient and exhibits an intrinsic superoxide dismutase-like activity preventing both the occurrence of potentially harmful heme-protein-associated free radical species and the release of Hb degradation products.

Recently a safety study in 60 renal grafts using HEMO2life® as additive to organ preservation solution (Oxyop study, NCT02652520) was completed, that confirmed that the use of HEMO2life® is safe for patients and grafts.

In the Oxyop study, even if the protocol was not designed to show a benefit of the use of HEMO2life®, significantly less delayed graft function (DGF) and a shorter renal function recovery was observed.

The present research focuses on the efficacy of HEMO2life®, which is an oxygen carrier added in preservation solution in kidney transplantation.

primary_purpose: Other

ipd_sharing_description: All collected data that underlie results in a publication

location_facility:
Clermont-Ferrand
La Réunion
Lille
Besançon
Reims
Association Hopital Foch
Lyon
Nantes
Rennes
Angers
APHP Henri Mondor
Paris La Salpétrière
Poitiers
Dijon
Nancy
Saint-Etienne
Tours
Bordeaux
Caen
APHP Bicêtre
Rouen
Strasbourg
CHRU de Brest
Grenoble
Limoges
Nice
Toulouse
Marseille
APHP Necker
Montpellier
APHP Saint-Louis
Amiens


title: Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

acronym: MPN-BIOCLOT

summary: Thrombosis is the main cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPN). However, the pathogenesis of thrombosis in MPN is still largely elusive. Neutrophils can release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". NETs are known to be procoagulant. Our main objective is to quantify NETs biomarkers expression in MPN patients and define if they could be used as prognostic factors in the outcome of thrombosis in these patients.

lead_sponsor: University Hospital, Bordeaux

location_facility: Hôpital Européen Georges Pompidou - APHP

location_facility: CHU Bordeaux, Hématologie Clinique et Thérapie Cellulaire

intervention_type: Biological


title: LONsurf and G-CSF Use: Being On A Right Dose-intensity to Optimize Treatment Efficacy

acronym: LONGBOARD

summary: Prospective cohort of patients treated with trifluridine/tipiracil, maximal sample size 250 patients. It is expected, that 89 patients will experience a grade 3-4 neutropenia and will be included in the phase II.

location_facility:
Hôpital Henri Mondor
Centre Georges François Leclerc
Groupe Hospitalier Pitié Sapêtrière
CHU Robert Debré
Hôpital Nord Franche Comté
Hôpital Privé Jean Mermoz
Hôpital Cochin
CHU Amiens
Centre hospitalier de Chauny
CHRU Jean Minjoz
Hôpital Haut Lévêque
Polyclinique Sainte Côme
Institut de cancérologie de l'Ouest
Hôpital Layne
Hôpital Saint Antoine
CHU Poitiers
Hôpital Franco-Britannique
Hôpital Européen
CHD Vendée
Polyclinique Bordeaux Nord
Clinique de Flandre
centre Pierre Curie


title: Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion: a Randomized Controlled Multi-center Trial

acronym: ADAPT

summary:
Sepsis induces both a systolic and diastolic cardiac dysfunction. The prevalence of this septic cardiomyopathy ranges between 30 and 60% according to the timing of assessment and definition used. Although the prognostic role of septic cardiomyopathy remains debated, sepsis-induced left ventricular (LV) systolic dysfunction may be severe and associated with tissue hypoperfusion, while it appears to fully recover in survivors. Accordingly, optimization of therapeutic management of septic cardiomyopathy may contribute to improve tissue hypoperfusion in increasing oxygen delivery, and to reduce related organ dysfunctions in septic shock patients.

Echocardiography is currently the recommended first-line modality to assess patients with acute circulatory failure.

Current Surviving Sepsis Campaign strongly recommends Norepinephrine as the first-choice vasopressor in fluid-filled patients with septic shock. In contrast, the use of Dobutamine is only suggested (weak recommendation, low quality of evidence) in patients with persistent tissue hypoperfusion despite adequate fluid resuscitation and vasopressor support. Levosimendan, an alternative inodilator, has failed preventing acute organ dysfunction in septic patients and has induced more supraventricular tachyarrhythmias than in the control group. Data supporting Dobutamine in this setting are scarce and primarily physiologic and based on monitored effects of this drug on hemodynamics and indices of tissue perfusion.

No randomized controlled trials have yet compared the effects of Dobutamine versus placebo on clinical outcomes. In open-labelled, small sample trials, the ability of septic patients to increase their oxygen delivery during Dobutamine administration appears to be associated with lower mortality.

The tested hypothesis in the ADAPT trial is that Dobutamine will reduce tissue hypoperfusion and associated organ dysfunctions in patients with septic shock and associated septic cardiomyopathy. In doing so, it may participate in improving clinical outcomes.

lead_sponsor: University Hospital, Limoges

location_facility:
Lille University Hospital
Dijon university hospital
Montpellier University Hospital
Angouleme Hospital
Hôpital Cochin - service de Réanimation
University Hospital
Poitiers University Hospital
Argenteuil Hospital
Limoges University Hospital
Aphp - Henri Mondor
CHU Orléans - service de Réanimation
Aphp - Ambroise Paré
Nice University Hospital
CHU Tours - Service de Réanimation
Le Mans Hospital
CHU Strasbourg - service de Réanimation
CHU de Nancy


title: Comparison of Corticosteroids Versus Placebo on Duration of Ventilatory Support During Severe Acute Exacerbations of COPD Patients in the Intensive Care Unit: a Multicentre Randomized Controlled Trial

acronym: Corticop

summary: The main objective of this study is to determine if the systemic (intravenous) administration of corticosteroids, as compared to placebo, increases the number of ventilator-free days (VFD) and alive at day 28 in COPD patients admitted to an ICU, a step-up unit or a respiratory care unit for an ACRF requiring ventilatory support, either invasive or non-invasive.

lead_sponsor: Versailles Hospital

location_facility: André Mignot Hospital, Intensive care unit


title: Observational Retrospective Cohort Study in Patients With Relapsed Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Treated With Olaparib Following Response to Platinium-based Chemotherapy

acronym: RETROLA

summary: This is a national, multi center, retrospective observational cohort study that will be carried out by reviewing the medical records of patients with relapsed epithelial ovarian, fallopian tube, or peritoneal cancer treated with olaparib following response to platinum-based chemotherapy.

time_perspective: Retrospective

lead_sponsor: ARCAGY/ GINECO GROUP

location_facility: Institut de Cancérologie Lucien Neuwirth

location_facility: Groupe Hospitalier Mutualiste de Grenoble

location_facility: ICL Institut de Cancérologie de Lorraine

location_facility: Clinique Mutualiste de l'Estuaire, Cité Sanitaire

location_facility: Hôpital Morvan - Centre Hospitalier Universitaire


title: Phase II, Open Label Study of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC) for Advanced Breast Cancer Patients, With Biomarkers Analysis to Characterize Response/Resistance to Therapy

acronym: DAISY

summary: Multicenter, open-label phase II trial assessing the efficacy of DS-8201a monotherapy in patients with metastatic breast cancer.

lead_sponsor: UNICANCER

location_facility: Institut de Cancérologie de l'Ouest - Site René Gauducheau

location_facility: Institut de Cancérologie de l'Ouest - Site Paul Papin

location_facility: Institut de Cancérologie Strasbourg Europe (ICANS)

location_facility: Institut Régional du Cancer Montpellier (ICM)

location_facility: Centre Hospitalier Universitaire Dupuytren


title: Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol With Dexamethasone Implant Loading Dose in Patients With Diabetic Macular Edema

acronym: LOADEX

summary:
Nowadays, steroids and anti-VEGF are the first line treatment for diabetic macular edema. Ozurdex is the most frequently used steroid and has label for both first and second line treatment. Ozurdex treatment paradigm for patients with diabetic macular edema is to inject patient only in case of huge recurrence. The risk of this scheme is a progressive loss of vision due to photoreceptors loss. A more pro-active regimen, as it already exists for anti-VEGF treatment, would allow a better patient management. A new treatment paradigm consisting in a loading dose of 2 injections within 3 months, followed by a PRN (Pro Re Nata) regimen with strict retreatment criteria and minimal time limit of 3 months between two injections should result in a better visual acuity gain and a limited augmentation of the number of injections (which will remain lower than the number observed for anti-VEGF treatment).

The investigators have therefore chosen a pilot study to investigate the impact on efficacy and on the number of intravitreal injections (IVI) of such a scheme.

location_facility: Hôpital d'instruction des armées Desgenettes

location_facility: Centre Monticelli Paradis d'ophtalmologie

location_facility: CHU Toulouse - Hôpital Pierre Paul Riquet

location_facility: Hospices Civils de Lyon - Hopital de la Croix Rousse

location_facility: Centre Hospitalier National d'Ophtalmologie des XV XX


type: Registry Identifier

title: Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients - a GETUG-AFU Phase III Randomized Controlled Trial

acronym: PRESTO

summary:
INDICATION: Oligometastatic hormone-sensitive prostate cancer patients. METHODOLOGY: Open label, double arm, randomized 1:1, multicenter phase III study.

PRIMARY OBJECTIVE: To assess the efficacy of ablative radiotherapy (SBRT applied to all oligometastases) administered to all gross tumor sites (metastases and prostate if applicable), in oligometastatic hormone-sensitive prostate cancer patients.

ReferenceCitation: Petrelli F, Ghidini A, Ghidini M, Bukovec R, Trevisan F, Turati L, Indini A, Seghezzi S, Lonati V, Moleri G, Tomasello G, Zaniboni A. Better survival of patients with oligo- compared with polymetastatic cancers: a systematic review and meta-analysis of 173 studies. Version 4. F1000Res. 2021 May 27 [revised 2022 Jan 1];10:423. doi: 10.12688/f1000research.52546.4. eCollection 2021.

ipd_sharing_description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

intervention_type: Radiation


title: A Phase II Non-randomized, Single Group Assignment, Open-label, Multicenter Study of Efficacy and Safety of Lorlatinib Monotherapy After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer

acronym: ORAKLE

summary: Crizotinib is a first-generation ALK tyrosine kinase inhibitor (ITK-ALK). It is the standard first-line treatment for patients with advanced NSCLC with ALK gene rearrangement. Alectinib, ceritinib and brigatinib are second-generation ITK-ALK. They have been shown to be effective in the first line of treatment in randomized trials. Alectinib has shown superiority to crizotinib as the first line of treatment in three randomized therapeutic trials, positioning this ITK-ALK as the treatment of choice in first-line treatment. Despite the effectiveness of these new treatments, all patients will virtually experience a relapse. There is no data on second-generation TKI-ALK resistance mechanisms when given as first-line treatment and the best therapeutic strategy for progression is undefined.

location_facility:
Annecy - CH
Marseille - AP-HM Hôpital Nord
Nantes - CRLCC
Lyon - CRLCC
Boulogne - Ambroise Paré
Montpellier - CHU
Créteil - CHI
Saint Quentin - CH
Paris - Curie
Lille - Hôpital Calmette
Toulouse - CHU
Strasbourg - Nouvel Hôpital Civil
Vandoeuvre-lès-Nancy - CRLCC
Dijon - CRLCC
Angers - CHU
Grenoble - CHU
Orléans - CHR
Mulhouse - GHRMSA
Montpellier - Clinique
Bordeaux - CHU Hôpital Haut-Lévèque
Paris - APHP - Hopital Tenon
Toulon - CHI
Besançon - CHU
Caen - CHU Côte de Nacre
Le Mans - CHG
Paris - Hôpital Cochin
Suresnes - Hopital Foch
Colmar - CH
Bayonne - CH
Marseille - Institut Paoli Calmette
Lyon - URCOT
Paris - APHP Bichat


title: Memento-Plus : Long-term Follow-up of Cognitive and Functional Evolutions of Persons With Isolated Cognitive Complaints or Mild Cognitive Deficits

acronym: Memento-Plus

summary:
Dementia is a clinical syndrome that is the result of distinct underlying pathologies including Alzheimer's disease (AD). Despite more than two decades of research on prevention and treatment of dementia and aging-related cognitive decline, highly effective preventive and therapeutic strategies remain elusive.

Many features of dementia render it especially challenging. Indeed development of disease occurs insidiously over the course of years or decade. In addition, the causes of dementia and determinants of its severity are likely multi-factorial.

To overcome these challenges and better understand the causes and course of AD and related disorders, long term follow-up studies of persons at high risk of dementia are required including multidimensional and harmonized assessment of risk factors, phenotypes (cognition, neuropsychiatric symptoms, physical health, self rated health) and endophenotypes (blood markers, genetic markers, neuroimaging markers).

This project proposes an extension of the follow-up of Memento participants over 5 to 10 years with of focus on cognitive outcomes and comorbidities.

location_facility: APHP Groupe Hospitalier Saint Louis Lariboisière Fernand Widal


title: Double-blind, Randomised, Parallel-group, Three-arm, Dose Range, Placebo-controlled, Proof-of-concept Study to Evaluate the Efficacy, Tolerability and Safety of a Combination of Cypropheptadine and Prazosin on Alcohol Consumption in Patients With Severe Alcohol Use Disorder

acronym: COCKTAIL

summary:
Double-blind randomised, parallel-group, three-arm, multicentre, placebo-controlled study The primary objective is to demonstrate the superiority of the combination of Periactine® (cyproheptadine 8 mg/day or 12 mg/day) and Alpress® (prazosin 5 mg/day or 10 mg/day) over placebo on the reduction of the total alcohol consumption (TAC), in alcohol-dependent patients.

180 patients will be randomised into the two treatment groups (N=60 in the low-dose group and N=60 in the high-dose group) and the placebo group (N=60).

lead_sponsor: Kinnov Therapeutics

location_facility: Centre de Soins, d'Accompagnement et de Prévention en addictologie Bizia

location_facility: Centre Hospitalier Universitaire de Dijon - Service d'addictologie

location_facility: Centre Hospitalier Régional Universitaire Saint Eloi - Service d'addictologie et complications somatiques

location_facility: Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou - Centre hépato-digestif

location_facility: Centre Hospitalier de la Côte Basque - Service d'addictologie

location_facility: Centre Hospitalier Universitaire de Nantes - site Hôtel-Dieu

location_facility: Centre Hospitalier Universitaire de Clermont-Ferrand

location_facility: Centre d'Addictologie "Pierre-Fouquet" - CHD La Candélie

location_facility: Centre Hospitalier de Pau - Unité d'addictologie

location_facility: Centre Hospitalier Régional d'Orléans - Hôpital La Source - Service d'hépato-gastro-entérologie et oncologie digestive

location_facility: Centre Hospitalier Intercommunal de Créteil - Service Hépato-Gastro-entérologie

location_facility: Centre Hospitalier Universitaire de Lyon - Hôpital de la Croix Rousse

location_facility: Centre hospitalier Esquirol - Pôle d'addictologie en Limousin

location_facility: CHU Provences-Alpes Côte d'Azur Hôpital Publique

location_facility: Association Hospitalière de Bourgogne Franche-Comté

location_facility: Service Universitaire d'Addictologie de Lyon - Centre Hospitalier Le Vinatier

location_facility: Centre Hospitalier universitaire de Nice - Hôpital Archet II


title: A Phase II Single-arm Trial Evaluating Safety and Efficacy of Durvalumab in ECOG Performance Status 2-3, Treatment-naive, Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC) and High PD-L1 Tumor Expression

acronym: SAVIMMUNE

summary:
Immunotherapeutic approaches targeting immune checkpoint proteins PD-1/PD-L1 have recently demonstrated clinical efficacy in several cancer types, and have changed the therapeutic landscape in metastatic melanoma or non-small cell lung cancer (NSCLC).

The monoclonal anti-PD-1 antibody nivolumab has been registered by both FDA (Food and Drug Administration) and EMA (European Medicine Agency), for metastatic NSCLC patients, after failure of a prior platinum-based chemotherapy.

The approval was based on the results of phase III clinical trials in metastatic NSCLC. But all the trials only enrolled patients with good general condition, PS (Performance Status) 0 or 1. However, the prevalence of poor PS patients at time of diagnosis is high in lung cancer patients.

For patients with metastatic NSCLC and PS 3, there is no standard treatment except best supportive care, since all trials that accrued unselected PS 3 patients fail to prove any survival advantage, and most PS >3 patients die within 2 to 4 months from diagnosis. Indeed, these patients are currently excluded from clinical trials. Specific dedicated clinical trials and treatment guidelines for this patient population are urgently needed, taking into account for the high prevalence of such patients.

location_facility: Nancy - Institut de Cancérologie de Lorraine


title: Randomised Phase 2 Trial Testing the Addition of Upfront Stereotactic Radiosurgery to Binimetinib Encorafenib Pembrolizumab Compared to Binimetinib Encorafenib Pembrolizumab Alone in BRAFV600 Mutation-positive Melanoma With Brain Metastasis

acronym: BEPCOME-MB

summary: This study evaluates the addition of stereotactic radiosurgery (SRS) to the combination of binimetinib + encorafenib + pembrolizumab in the treatment of BRAFⱽ⁶⁰⁰ mutation-positive melanoma with brain metastases (MBM).

ipd_sharing_description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

location_facility: CLCC - IUCT-0 / Institut Claudius Regaud

location_facility: CLCC - Institut de Cancerologie de l'Ouest - Nantes

location_facility: APHP - L'hôpital de la Pitié-Salpêtrière

location_facility: CLCC - Institut de Cancerologie de Montpellier


title: A Multicentre, Open-label Phase II Trial Evaluating the Safety and Efficacy of Ponatinib Induction Followed by Imatinib Maintenance in Adult Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) ≤ 65 Years

acronym: TIPI

summary:
The investigators hypothesize that, in newly diagnosed de novo chronic phase CML patients, an induction treatment with ponatinib for 6 months should increase the rate of patients reaching a stable MR4.5 allowing cessation of imatinib treatment.

The investigators proposal is to conduct a multicenter, Phase II trial to evaluate the safety, clinical and biological activity of an induction treatment with ponatinib for 6 months, followed by a consolidation treatment with imatinib in newly diagnosed de novo chronic phase CML patients.

lead_sponsor: Centre Leon Berard

location_facility: Institut de cancérologie Strasbourg Europe

location_facility: Institut de Cancérologie Lucien Neuwirth

location_facility: CHU Nîmes Caremeau - Institut de Cancérologie du Gard

location_facility: Institut D'Hematologie de Basse Normandie


title: Evaluation of the Impact of the SMART ANGEL ™ Device on Follow-up at Home Following Major or Intermediate Outpatient Surgery: Randomized Controlled Open-label Trial

acronym: SMART ANGEL 2

summary: The investigators hypothesize that by monitoring and analyzing physiological parameters (heart rate, blood pressure, saturation) and well-being (pain, nausea, vomiting, comfort) the SMART ANGEL ™ device improves the quality of care after major or intermediate outpatient surgery. This active surveillance will result in a decrease in the rate of unplanned recourse (hospitalization, consultation, telephone call).

lead_sponsor: Centre Hospitalier Universitaire de Nīmes

location_facility: Centre hospitalier universitaire Amiens-Picardie


title: A Multicentre Phase II, Open-label, Non-randomized Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/- Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

summary: The objective of this study is to assess the efficacy of the combination of Platinum (carboplatin or cisplatin), Pemetrexed, Atezolizumab+/- Bevacizumab if eligible, in stage IIIB/IV non-squamous non-small cell lung cancer patients with progression-enhancing mutations following targeted therapies.

lead_sponsor: Centre Francois Baclesse

location_facility: Hôpital Haut Lévêque,Centre François Magendie


title: Cohort Study to Evaluate the Clinical Features of Patients With Epithelial Ovarian Cancer Depending on Tumoral Mutation of BRCA or Beyond BRCA Genomic Molecular Abnormalities

acronym: GREAT

summary: This is a prospective observational French multicenter cohort in patients with ovarian and/or primitive peritoneal and/or fallopian tubes carcinoma, histologically confirmed, with an advanced stage at diagnosis (stage III to IV FIGO 2014). The objective is to constitute a clinico-biological database that allows to correlate clinical and progressive features of ovarian cancer patients based on tumor genomics and molecular detected abnormalities.

location_facility: CHU Saint-Etienne - Pôle de Cancérologie

location_facility: Centre Hospitalier Sud Francilien (Site Gilles de Corbeil)

location_facility: Institut de Cancérologie du Gard - ONCOGARD

location_facility: Centre de Cancérologe du Grand Montpellier

location_facility: Institut de Cancérologie de Bourgogne - GRReCC

location_facility: Institut de Cancérologie de Lorraine (ICL) - Centre Alexis Vautrin

location_facility: CHU Grenoble Alpes - Site Nord (La Tronche)

location_facility: Hôpital Privé Drôme Ardèche - Clinique Pasteur

location_facility: Centre de Radiothérapie et d'Oncologie de Moyenne Garonne (CROMG)

location_facility: CHRU de Montpellier - Hôpital Saint-Eloi

location_facility: Clinique du Mousseau (CMCO) - Ramsay Santé

location_facility: Centre Hospitalier Intercommunal de Fréjus Saint Raphael

location_facility: Groupe Hospitalier public du Sud de l'Oise (GHPSO)

location_facility: Centre d'Oncologie et de Radiothérapie 37

location_facility: Centre Hospitalier Général d'Aix-en-Provence

location_facility: Centre Hospitalier Départemental de Vendée

location_facility: Centre Médicale Sainte Feyre Alfred Leune

location_facility: Groupe Hospitalier Diaconesses - Croix Saint-Simon

location_facility: Polyclinique de Limoges - Clinique Chenieux

location_facility: Clinique Pasteur - Groupe Oncorad Garonne

location_facility: ICANS - Institut de cancérologie Strasbourg Europe

location_facility: Hôpital d'Instruction des Armées Saint-Anne

location_facility: Hôpitaux Drôme Nord - Centre Hospitalier Romans

location_facility: Institut de Cancérologie de l'Ouest - ICO

location_facility: Groupe Hospitalier Bretagne Sud - Hôpital du Scorff


title: Evaluation of Risk-Adapted and MRD-Driven Strategy for Untreated Fit Patients With Intermediate Risk Chronic Lymphocytic Leukemia: a Randomized Phase II Trial Comparing FCR and a Chemo-free Combination of Venetoclax and Ibrutinib

acronym: ERADIC

summary:
The aim of this study is to test the potential benefit of an innovative combination of targeted therapy over the standard the immunochemotherapy (FCR). The interest in this study resides in an MRD driven discontinuation of the novel agents, and a fixed maximum duration of these agents. This design allows a true comparison of the efficacy of IV with the immuno-chemotherapy at 2 years of treatment and later.

Finally, other trials propose to include to all risk categories of patients, and we are developing here a stratification preventing the dilution of the results. The intermediate risk patients are the ones for which alternative to chemotherapy is critical, as chemotherapy is likely to alter the clonal evolution of their disease, whereas the low risk patients are already doing well with standard treatment and are likely to benefit from other therapies as well. The high risk patients, id est patients with 17p deletion and or TP 53 mutational status responded very well to new drugs as BTK inhibitors or BLC2 inhibitors.

ipd_sharing_description: At the end of the study, the participant data (DPI) collected in this study may be made available to other researchers who request it from the sponsor and if the rationale is the improvement of knowledge in the CLL. The provision will be evaluated by the sponsor.

lead_sponsor: French Innovative Leukemia Organisation

location_facility: Hôpital Avicenne - Centre de Recherche Clinique

location_facility: Centre Hospitalier Regional Metz Thionville

location_facility: Institut de Cancérologie Lucien Neuwirth

location_facility: CHU Estaing - Hématologie Clinique Adulte

location_facility: Hôpital Bretonneau - Hématologie et Thérapie Cellulaire

location_facility: Hôpital de la Milétrie - Hématologie et Thérapie Cellulaire

location_facility: CHU Pontchaillou - Hématologie Clinique BMT-HC

location_facility: Centre Henri Becquerel - Service Hématologie Clinique


title: A Phase III Study Comparing Lenalidomide and Subcutaneous Daratumumab (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd) in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy

lead_sponsor: University Hospital, Lille

location_facility:
Ch Blois Simone Veil
Oncopole Chu Toulouse
Chu de Caen Normandie
Chu Dijon Bourgogne
Chu de Tours
Centre Hospitalier de Perigueux
Chi Mont de Marsan Et Pays Des Sources
Chru Jean Minjoz
Gpe Hospitalier La Rochelle-Re-Aunis
Ch Fleyriat
Chru Brest Site Hopital Morvan
Centre Hospitalier Saint-Malo
Chu Montpellier
Chu de Grenoble
Ch Chartres Louis Pasteur-Le Coudray
Chru Rennes Site Pontchaillou
Chu de Nantes Site Hotel Dieu Hme
Chu de Nice Hopital de L'Archet
Institut Paoli Calmettes
Hôpital Claude Huriez, CHU
Hopital Haut-Leveque - Chu
Centre Hospitalier de Saint Quentin
Hopital Prive Sevigne - Cesson

summary: This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital team work on a medical research study) study in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) and who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT). The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT