Cost-effectiveness of full versus targeted monitoring of randomized controlled trials

International audienc

A survey on French hospital physicians' certification to the Good Clinical Practices

International audienc

Ensuring quality control in a clinical trial during the COVID-19 pandemic: The experience of the Inserm C20-15 DisCoVeRy study in France

International audienceMeeting Abstract PM2-02

Ledipasvir/sofosbuvir chez les patients co-infectés par le VIH et un VHC de génotype 1 prétraités par un inhibiteur de la protéase NS3/A4 du VHC (étude ANRS HC31 SOFTRIH)

National audienceIntroduction L’association fixe d’antiviraux directs ledipasvir/sofosbuvir (LDV/SOF), disponible sous la forme d’un comprimé unique, n’a pas été étudiée spécifiquement chez les patients chroniquement infectés par un VHC de génotype 1 (G1), co-infectés par le VIH et en échec d’un traitement préalable incluant un inhibiteur de la protéase (IP) NS3/A4 du VHC. Nous avons évalué l’efficacité et la tolérance de cette combinaison dans cette population de patients, historiquement considérés comme très difficiles à traiter (étude ANRS HC31 SOFTRIH). Patients et méthodes Les patients infectés de manière chronique par un VHC G1, co-infectés par le VIH et sous traitement antirétroviral stable (ARV), en échec d’un traitement anti-VHC antérieur par interféron pégylé/ribavirine/IP NS3/A4 ou ayant interrompu précocement ce traitement pour intolérance, ont été inclus dans cette étude prospective. Tous les patients ont reçu la combinaison fixe LDV/SOF (90 mg/400 mg), une fois par jour pendant 12 semaines ou 24 semaines en cas cirrhose hépatique. Les patients pouvaient également recevoir les ARVs suivants : tenofovir, emtricitabine,lamivudine, raltegravir, efavirenz, rilpivirine, enfuvirtide. Les critères de jugement d’efficacité étaient l’obtention d’une réponse virologique soutenue, définie par un ARN VHC indétectable 4 semaines (RVS4) ou 12 semaines (RVS12, critère principal) après l’arrêt du traitement. La survenue d’effets indésirables (EIs) et les paramètres biologiques standards incluant la numération des lymphocytes CD4 et l’ARN VIH ont été étudiés. Résultats Soixante-huit patients avec un G1a (82,5 %), un G1b (13 %) ou un autre G1 (4,5 %) ont été inclus : hommes 79 % ; âge moyen 52 ans ; médiane de l’ARN VHC (6,2 Log UI/mL) et des lymphocytes CD4 (629/mm3) à l’inclusion ; cirrhose compensée (40 %). Soixante-cinq patients étaient évaluables pour les critères virologiques. Soixante-deux patients (95,4 %) ont obtenu une RVS4 (prélèvement sanguin non disponible chez 1 patient, ARN VHC détectable inférieur au seuil de quantification chez 2 patients). Tous les patients (100 %) ont obtenu une RVS12. Deux patients ont présenté un rebond virologique VIH confirmé. Aucun patient n’a interrompu précocement le traitement de l’étude pour intolérance. Les EIs constatés chez plus de 10 % des patients étaient les suivants : fatigue (19,1 %), pression artérielle élevée (14,7 %), céphalées (11,8 %). Conclusion Si les études ERADICATE [1] et ION-4 [2] ont récemment montré une efficacité et une tolérance très bonnes de l’association LDV/SOF chez les patients co-infectés par le VIH, notre étude apporte des résultats supplémentaires chez les patients historiquement considérés comme très difficiles à traiter, incluant ceux présentant une cirrhose hépatiqu

A survey on French hospital physicians' certification to the Good Clinical Practices

National audienceGood clinical practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials. Before the start of a clinical trial, investigators commit to perform the research in accordance with GCPs, regulatory dispositions and protocol. The sponsors are responsible for investigators’ selection and for controlling their skills. Whereas industrial sponsors systematically require a certificate of GCP training, academic sponsors seem to be less demanding. We have carried out two surveys between April and June 2018. A first questionnaire was sent to the 40 French academic directions of clinical research and innovation in order to determine their requirements about the GCP training of the investigators participating in their trials. The second questionnaire was transmitted to physicians of the “Bretagne recherche clinique hospitalière network”: Rennes, Saint Malo, Saint Brieuc, Vannes, Lorient and Pontivy hospitals, in order to determine the GCP certification rate, and their needs in terms of clinical research training. Twenty-eight (70%) directions of clinical research answered the first survey, among which 18 (64%) required systematically the investigators’ GCP certification in case of category 1 interventional studies. This rate decreased for category 2 (50%) and non-interventional category 3 (18%) studies. A total of 345 physicians answered the second survey, among which 263 (76%) had already been clinical trial investigators. However, only 29% of allphysicians and 54% of those who had been principal investigator were certified for GCP training. These results support the need for large campaigns of GCP training in public hospitals

HCV eradication does not protect from fibrosis progression in patients with fibrosing cholestatic hepatitis after liver transplantation

International audienceINTRODUCTION: Hepatitis C virus (HCV) may recur after liver transplantation (LT) in the severe form of fibrosing cholestatic hepatitis (FCH). The prognosis dramatically improved by the use of direct acting antivirals (DAAs). The aim of the present study was to describe the change in histological features of FCH after virological eradication. METHODS: From the ANRS CUPILT cohort we included 17 patients who presented FCH and at least two graft biopsies, one before DAA-treatment and one after. A single expert pathologist, blinded for clinical outcome, retrospectively confirmed the diagnosis of FCH and progression of fibrosis. RESULTS: Diagnosis of FCH was made after a median [IQR] 6.0 [3.1-11.8] months after LT, and the median interval between diagnosis and onset of treatment was 1.2 [0.7-6.1] months. The rate of viral eradication was 94.1%. The median delay between the pre-treatment and the treatment biopsies was 12.5 [11.1-20.0] months. Between the end of treatment and the second biopsy, the delay was 5.3 [0.6-7.4] months. Fibrosis stage worsened in 10 patients (58.8%); 6 patients had cirrhosis (35.3%). Chronic rejection appeared in 4 (23.5%) patients. CONCLUSION: Our results suggest that, despite viral eradication in patients presenting FCH after LT, fibrosis progression was observed in half of patients. This should encourage monitoring fibrosis progression despite HCV cure

O109 : Treatment of severe HCV-recurrence after liver transplantation using sofosbuvir-based regimens: The ANRS CO23 CUPILT study

International audienceno abstrac

Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients after Liver Transplantation: Results from the ANRS CO23 CUPILT Study

International audienceBackground - A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation. Methods - Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort. Their antiviral treatment combined SOF, daclatasvir with or without ribavirin (n = 10/n = 6), or SOF, ledipasvir with or without ribavirin (n = 2/n = 11). Results - The median delay between liver transplantation and treatment initiation was 37.5 months (interquartile range [IQR], 14.4-99.2). The breakdown of HCV genotypes was G1, 22 patients (75.9%); G3, 3 patients (10.3%); and G4, 4 patients (13.8%). The treatment indications were HCV recurrence (≥ F1 n = 23) or fibrosing cholestatic hepatitis (n = 6). Before starting SOF, the HCV viral load and CD4 count were 6.7 log10 IU/mL (IQR, 5.9-7.2) and 342 cells/mm (IQR, 172-483), respectively. At week 4, the HCV viral load was less than 15 IU/mL in 12 (42.9%) patients. The overall sustained virological response 12 was 96.6%. No significant drug-drug interactions were observed. Conclusions - SOF-based treatment regimens produced excellent results in HIV/HCV coinfected patients after liver transplantation, suggesting an important change in their prognosis

Should we keep using Ribavirin to Treat Hepatitis C Recurrence after Liver Transplantation? Results from the CO23 ANRS Cupilt Study

International audienceEASL International Liver Congress, APR 13-17, 2016, Barcelona, SPAI