Chronic Hepatitis C Treatment by Pegylated Interferon and Ribavirin in Naive Egyptian Patients (ANRS 1211)

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase

Completed

Phase 3

Conditions

Chronic Hepatitis C

Treatments

Drug: pegylated interferon alpha2a

Drug: ribavirin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00158496

ANRS 1211

Details and patient eligibility

About

Chronic hepatitis C is a liver disease related to a virus: hepatitis C virus (HCV). The type of HCV present in Egypt (genotype 4), has the reputation to respond poorly to Interferon treatment at the chronic stage. Pegylated Interferon is a new form of Interferon that stays in the body for longer time and allows the patient to take less injection per week. It has proved to be more effective than standard Interferon. The combination of two drugs, Interferon and Ribavirin, is considered to be the best treatment available for chronic hepatitis C.

Full description

Egypt is the country with the highest HCV prevalence worldwide, and the number of infected Egyptians is estimated around 8 million. The HCV genotype circulating in Egypt is genotype 4. This genotype has the reputation, based on the few available data, to respond poorly to treatment. This study will estimate the safety and efficacy of the combination of peg-IFNα-2a plus Ribavirin, in Egyptian patients with chronic hepatitis C. This treatment has been chosen based on its better expected efficacy compared to pegylated interferon alone.

The primary objective of the study is to assess the efficacy and tolerance of the combination of pegylated interferon (peg-IFNα-2a) plus ribavirin in Egyptian patients with chronic hepatitis C and with no prior treatment for HCV.

Methods: Open trial. Follow-up duration: 72 weeks. Enrolment duration: 18 months. Total trial duration: 3 years and a half, including trial analysis (carried out in the 6 months following the follow-up completion of the last patient). Total number of patients: 100. Precision around the expected efficacy rate (40% in intention-to-treat analysis): 9.6%.

Treatment strategy: Peg-IFNα-2a 180microg/week for 48 weeks, Ribavirin at least 11 mg/kg/day for 48 weeks Main inclusion criteria: HCV RNA positive by PCR; METAVIR score : >A2 and >= F1 or >= A1 and > F2; ALAT over 1.5*N; no prior treatment with IFNalpha, PEG-IFNalpha and ribavirin Main exclusion criteria : Liver disease other than hepatitis C; advanced liver disease; negative HCV RNA.

Patient from a cohort follow-up conducted in a village in rural Egypt with High HCV prevalence (Menoufia governorate) will be proposed to participate in the trial. Pre-enrolment investigations, liver biopsy, and patients follow-up will be carried out at a local hospital. Blood test analyses will be carried out under the responsibility of Hepatitis Virology Reference Laboratory at the National Hepatology and Tropical Medicine Institute, Cairo; trial monitoring will be carried out by the Department of Community Medicine of Ain Shams; methodological assistance from the "Unite des Maladies Emergentes" at Pasteur Institute and INSERM U444, Paris.

Treatment for patients with HCV RNA by qualitative PCR still positive after 24 weeks of the combination Peg-IFNα-2a with ribavirin, will be stopped.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

HCV antibodies using a third generation test
HCV RNA positive by PCR
Liver biopsy in the past 18 months with METAVIR score over A2 and over or equal to F1, or over or equal A1 and over F2
ALT over 1.5 time the normal range in the 24 weeks prior to inclusion (Week-28; W-2);
Patients never treated with ribavirin, IFNalpha or PEG-IFNalpha
Normal albumin
Prothrombin time over or equal to 60 percent
Normal bilirubin
Alpha-foeto-protein under or equal to 3 times the normal range for the laboratory
HBs antigen negative
Two negative Kato test (for S.mansoni) three days apart
Hemoglobin over or equal 11g/dl,
Leucocytes over or equal 3000/mm3
Neutrophils over or equal 1500/mm3
Platelets over or equal 100 000/mm3
Blood creatinin over or equal 150 micromol/l
Normal TSH
Anti-nuclear antibodies under 1/160
Fasting blood sugar between 70-115mg/dl (if glucose intolerance or diabetes: HbA1C <= 8,5%)
Normal ophthalmologic examination in patients with history of blood pressure and/or diabetes
Effective contraception during the treatment period
No breastfeeding during the study period.
Signed informed consent

Exclusion criteria

Co-infection with hepatitis B (positive HBs antigen)
Hemochromatosis
Alpha-1 anti-trypsin deficiency
Wilson disease
Alcoholism-related liver disease
Gilbert disease
Alcohol intake over 50g/day for males and 40 g/day for females
Ongoing intravenous drug use
Aggravated liver cirrhosis (history or presence of ascitis, oesophageal varicosis, liver encephalopathy)
Hepatocellular carcinoma
Psychiatric disease: history of severe nervous breakdown or severe psychiatric diseases such as major psychosis, suicidal ideas, suicide attempts...
Epilepsy
Auto-immune disease
Heart disease in the six months preceding enrolment - patients with significant changes at EKG
Uncontrolled diabetes
Chronic respiratory insufficiency with hypoxemia <10 kPa
Medical or surgical condition, non-stabilised, with life expectancy lower than two years.
Pregnancy or breastfeeding