Different Ribavirin Dosages and Different Duration of Treatment in Combination With PegInterferon in Patients With Genotype 2 and 3 (WRITE)

Study Overview
=================
Brief Summary
-----------------
WRITE study aim at identifying the effectiveness of an innovative individualized schedule of treatment as compared to standard regimen in patients with chronic HCV genotype 2 and 3.

Detailed Description
-----------------
The investigators are going to compare weight-based dosages of ribavirin, in combination with Peginterferon alpha-2a, with standard fixed dosages of 800 mg. Patients will be evaluated at week 4 with an assay of sensitivity of 15 IU/ml. Patients with week 4 response will discontinue treatment at week 12 in both arms. Patients with HCV RNA still detectable at week 4 and receiving 1000-1200 mg of ribavirin in arm A will discontinue treatment at week 24, whereas patients with HCV RNA still detectable at week 4 and receiving 800 mg of ribavirin in arm B will be treated till week 48. A standard treatment arm (C) including patients treated for 24 weeks with Peginterferon alpha-2a and fixed 800 mg ribavirin dosage will be used as control arm.

Official Title
-----------------
RCT Comparing Different Ribavirin Dosages and Durations of Treatment in Combination With Peginterferon in HCV Genotypes 2 and 3 (WRITE)

Conditions
-----------------
Chronic Hepatitis

Intervention / Treatment
-----------------
* Drug: Peginterferon alpha-2a + Ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with chronic hepatitis C virus (HCV) infection (both HCVAb and HCV RNA positive) Patients with HCV genotype 2 or 3 Age 18-70 years Naïve patients or previously treated only with standard interferon monotherapy Female patients of childbearing age who agree to avoid pregnancy during the period of treatment and 24 weeks after the end of treatment Exclusion Criteria: Previous treatment with ribavirin Cirrhosis (CHILD PUGH B and C) Evidence of Hepatocellular carcinoma Pregnancy Retinopathy class I or II Alcohol consumption > 40 gr/day Chronic cardiac or respiratory diseases HIV or HBsAg or HDV positivity Hemoglobin < 8.5 gr/dL WBC < 3.500/mm3 PLT < 80.000/mm3

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm C. Standard duration<br>Patients will be randomly assigned in 3:3:1 ratio to three treatment arms. In the standard treatment group (Arm C), patients will be treated for 24 weeks independently of the HCV RNA status at week 4 with Peginterferon alpha-2a at a dose of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 800 mg/day. Patients enrolled in Arm C will be treated for standard 24 weeks duration of treatment. | |
| Experimental: Arm A<br>Patients enrolled in Arm A will receive Peginterferon alpha-2a at a dosage of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 1000 mg/day for patients with a body weight < 75 kg or 1200 mg/day for those with a body weight > 75 kg. Patients with week 4 viral clearance (labelled as rapid virological responders, RVR) will be allocated to 12 week treatment duration (Arm A), whereas those without RVR will be treated for 24 weeks (Arm A) | Drug: Peginterferon alpha-2a + Ribavirin<br>* Administration of ribavirin at a dosage of 1000 or 1200 mg per day based on body weight < or > 75 kg for 24 weeks (Arm A). Treatment duration of 48 weeks with standard fixed dose of ribavirin (800 mg/day) (Arm B). These schedules will be compared with diagram of standard therapy with 800 mg daily of ribavirin for 24 weeks (Arm C)<br>* Other names: Copegus or Rebetol, Ribavirin Teva;|
| Experimental: Arm B<br>Patients enrolled in Arm B will receive Peginterferon alpha-2a at a dosage of 180 mcg weekly in combination with oral ribavirin administered at a dosage of 800 mg/day. Patients with week 4 viral clearance (labelled as rapid virological responders, RVR) will be allocated to 12 week treatment duration (Arm B), whereas those without RVR will be treated for 48 weeks (Arm B) | Drug: Peginterferon alpha-2a + Ribavirin<br>* Administration of ribavirin at a dosage of 1000 or 1200 mg per day based on body weight < or > 75 kg for 24 weeks (Arm A). Treatment duration of 48 weeks with standard fixed dose of ribavirin (800 mg/day) (Arm B). These schedules will be compared with diagram of standard therapy with 800 mg daily of ribavirin for 24 weeks (Arm C)<br>* Other names: Copegus or Rebetol, Ribavirin Teva;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological Response (SVR) | The primary measure of efficacy will be HCV RNA not detectable in serum samples 24 weeks after the end of therapy (SVR). | 6 months after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rapid virological response (RVR) | proportion of patients with undetectable HCV RNA 4 weeks after the start of treatment | On treatment week 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
genotypes 2 and 3, combination treatment, individualized treatment