Use of Direct-acting Antiviral to Treat HCV Recurrence After Liver Transplantation (ANRSCO23CUPILT) Infection (ANRSCO23CUPILT)

Cohort of Liver Transplanted Patients With Hepatitis C Virus Recurrence and Treated With Direct-acting Antiviral Agents

The purpose of this study is to evaluate the efficacy, safety and tolerability of direct-acting antivirals therapy in liver transplanted patients who experienced HCV recurrence.

This cohort is multicentric with constitution of biobank (plasma, serum) and the prospective collect of biological and clinical data's in the liver transplanted patients with recurrent HCV infection and treated with direct-acting anti-HCV agents.

Study Overview

• Status: Unknown
• Conditions: Liver Transplantation; HCV Recurrence; Direct-acting Antiviral Agents

• Study Type: Observational
• Enrollment (Actual): 699

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • Claire Fougerou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Liver transplant patients with recurrent hepatitis C virus infection treated with direct-acting antiviral agents and followed up in centers of transplantation of the university hospitals.

Description

Inclusion Criteria:

• Age > 18 years-old
• Liver transplanted patient
• Hepatitis C virus infection before transplantation
• HCV recurrence with a detectable HCV RNA before enrollment in cohort
• Use of at least one direct-acting antiviral agents with or without association with peginterferon and with or without association with ribavirin
• Treated by direct-acting antiviral agents or has been yet completed the treatment but still on follow up
• Affiliated to Health Insurance
• Written Signed consent form

Exclusion Criteria:

• Pregnant or breast-feeding female

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of sustained virological response 12 weeks after discontinuation of direct-acting anti-HCV therapy in liver transplanted patients with HCV recurrence	Sustained virological response (SVR) at 12 weeks after the end of the treatment (SVR defined as undetectable HCV RNA measured by PCR en real time at 12 weeks after antiviral therapy discontinuation)	12 weeks after discontinuation of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological responses at 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatment and 4,12,24,48 weeks after treatment discontinuation	Detectability of HCV RNA according to real time PCR	Baseline, 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatement and 4,12,24,48 weeks after treatment discontinuation
Tolerability of direct acting antiviral HCV agents	Clinical and laboratory parameters (hepatic, renal, hematological in particular) to assess safety and recording of adverse events	Baseline, 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatment and 4,12,24,48 weeks after treatment discontinuation
Drug-drug interactions	Trough blood concentration of immunosuppressive drugs	Baseline, 1,2,4,12,16, 24, 48 weeks during treatement and 4weeks after treatment discontinuation
To evaluate emergence of viral resistance to direct-acting antivirals agents		Baseline, 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatement and 4,12,24,48 weeks after treatment discontinuation
To establish predictive factors of treatment failure and of emergence of viral resistance	The rate of anticipated antiviral treatment discontinuation because of intolerability or of severe adverse events	Baseline, 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatement and 4,12,24,48 weeks after treatment discontinuation
Evaluate the incidence of graft loss and acute rejection	The rate of graft loss	Day 0, 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatement and 4,12,24,48 weeks after treatment discontinuation
Impact on concomitant therapy on virological responses and safety		Baseline, 1,2,3,4,6,8,12,16, 20, 24, 36, 48 weeks during treatment and 4,12,24,48 weeks after treatment discontinuation

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Georges Philippe Pageaux, Professsor, Hospital Saint Eloi

Publications and helpful links

General Publications

• Barrail-Tran A, Goldwirt L, Gele T, Laforest C, Lavenu A, Danjou H, Radenne S, Leroy V, Houssel-Debry P, Duvoux C, Kamar N, De Ledinghen V, Canva V, Conti F, Durand F, D'Alteroche L, Botta-Fridlund D, Moreno C, Cagnot C, Samuel D, Fougerou-Leurent C, Pageaux GP, Duclos-Vallee JC, Taburet AM, Coilly A. Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort. Eur J Clin Pharmacol. 2019 Nov;75(11):1555-1563. doi: 10.1007/s00228-019-02725-x. Epub 2019 Aug 5.
• Antonini TM, Coilly A, Rossignol E, Fougerou-Leurent C, Dumortier J, Leroy V, Veislinger A, Radenne S, Botta-Fridlund D, Durand F, Houssel-Debry P, Kamar N, Canva V, Perre P, De Ledinghen V, Rohel A, Diallo A, Taburet AM, Samuel D, Pageaux GP, Duclos-Vallee JC; ANRS C023 CUPILT study group. Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients After Liver Transplantation: Results From the ANRS CO23 CUPILT Study. Transplantation. 2018 Jan;102(1):119-126. doi: 10.1097/TP.0000000000001928.
• Leroy V, Dumortier J, Coilly A, Sebagh M, Fougerou-Leurent C, Radenne S, Botta D, Durand F, Silvain C, Lebray P, Houssel-Debry P, Kamar N, D'Alteroche L, Petrov-Sanchez V, Diallo A, Pageaux GP, Duclos-Vallee JC; Agence Nationale de Recherches sur le SIDA et les Hepatites Virales CO23 Compassionate Use of Protease Inhibitors in Viral C in Liver Transplantation Study Group. Efficacy of Sofosbuvir and Daclatasvir in Patients With Fibrosing Cholestatic Hepatitis C After Liver Transplantation. Clin Gastroenterol Hepatol. 2015 Nov;13(11):1993-2001.e1-2. doi: 10.1016/j.cgh.2015.05.030. Epub 2015 Jun 1.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 13, 2013
• First Posted (Estimate): September 17, 2013

Study Record Updates

• Last Update Posted (Estimate): February 2, 2016
• Last Update Submitted That Met QC Criteria: February 1, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: 2013-A00941-44