Clinical trial NCT00122629: Triple Therapy With Peg-Interferon Alfa-2b/Ribavirin Plus Amantadine Compared to Standard Peg-Interferon Alfa-2b/Ribavirin for Previous Hepatitis C Virus (HCV) Non Responders
Official title: Triple Therapy With Peg-Interferon Alfa-2b/Ribavirin Plus Amantadine Compared to Standard Peg-Interferon Alfa-2b/Ribavirin for Previous HCV Non Responders ANRSHC03 BITRI
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
peginterferon alfa-2b
ribavirin
Amantadine
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
Collaborators: name: Schering-Plough
First posted: 2005-07-22
Enrollment: 405
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Triple antiviral therapy with peg-interferon-alfa/ribavirin+amantadine was suggested to increase sustained virological response (SVR) rates in HCV non-responders to a standard interferon/ribavirin combination.

Patients with hepatitis C virus infection were eligible if they had failed to respond to a single previous 24 week cycle of interferon/ribavirin combination therapy. Non-response was defined as persistent HCV RNA in the serum during the last month of treatment.

This study tested the efficacy and safety of pegylated interferon alfa-2b with ribavirin and amantadine or a placebo for 48 weeks.

Detailed description: Triple antiviral therapy with peg-interferon-alfa/ribavirin + amantadine was suggested to increase sustained virological response (SVR) rates in HCV non-responders to a standard interferon/ribavirin combination.

The aim of this study is to determine if the addition of amantadine to PEG-IFN/ribavirin enhances SVR.

This study is a double blind, comparative, prospective multicenter, randomized study. Patients are recruited from 23 hepatology centers in France. The protocol was approved by the French ethical committee and all patients provided written informed consent. Eligible subjects are randomly assigned to the two treatment groups in equal proportions. The randomization process is generated by the Department of Biostatistics, Hospices Civils de Lyon, Lyon, France.

Main inclusion criteria are: elevated ALT, detectable HCV RNA, Metavir score over or equal to A1F1 and below or equal to F3. Patients received PEG-IFN 1.5µg/kg/week, ribavirin 800-1200mg/day and amantadine 200mg/day or placebo during 48 weeks.

The primary endpoint is a sustained virological response, defined as an undetectable HCV-RNA 24 weeks after treatment discontinuation (week 72). Secondary endpoints are the biochemical response at week 72 defined as ALT normalization; histological benefit; tolerance; and virological and biochemical responses during therapy at weeks 12, 24 and 48.

Eligibility criteria: Inclusion Criteria:

* Positive anti-HCV antibody test
* Patients who did not respond to treatment with standard interferon + ribavirin (HCV RNA+ by PCR in the last month of treatment)
* Compensated liver disease
* Neutrophil count over or equal to1000/mm3
* Platelet count over or equal to 100 giga/L
* Haemoglobin over or equal to 10g/dL
* Patients had to have undergone a post-treatment liver biopsy within a year, showing a METAVIR histological score over or equal to A1F1, without cirrhosis (fibrosis score below F4)
* ALT over N and HCV RNA+ at screening

Exclusion Criteria:

* Co-infection with hepatitis B or human immunodeficiency virus
* Any other cause of liver disease
* Active drug abuse, active alcohol consumption above 40g/day
* Organ grafts
* Presence of hepatocellular carcinoma
* Cardiovascular, metabolic, renal, haematological, neurological or psychiatric disease
* Patients with previous amantadine use
* Systemic immunosuppressive or antiviral treatment during the last 24 weeks and those with a history of interferon and/or ribavirin intolerance

Primary outcomes:
measure: Sustained virological response, defined as an undetectable HCV-RNA 24 weeks after treatment discontinuation at week 72
Secondary outcomes:
measure: Biochemical response at week 72 defined as ALT normalization
measure: Histological benefit
measure: Tolerance
measure: Virological and biochemical responses during therapy at weeks 12, 24 and 48
Other outcomes:
Locations:
city: Lyon Cedex
country: France
facility: Service d'Hépato-Gastroentérologie Hopital Hotel Dieu
Study officials:
affiliation: Hépato-Gastroentérologie Hopital Hôtel-Dieu LYON
name: Christian Trepo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laboratoire d'Informatique Médicale Lyon
name: P. ADELEINE, MD
role: STUDY_CHAIR
References: