To Evaluate the Safety and Efficacy of Sofosbuvir and Ribavirin in Patients With HCV (Genotype 3) Related Decompensated Cirrhosis

Study Overview
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Brief Summary
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In this prospective randomized trial, A Minimum of 300 consecutive patients of decompensated HCV (Hepatitis C Virus) related cirrhosis, presenting to the Institute of Liver and Biliary Sciences hospital will be included and those patients meeting the entry criteria received treatment with 400 mg of Sofosbuvir, administered orally once daily, and Ribavirin administered orally twice daily, with doses determined according to body weight(600 mg daily in patients with a body weight of ≤60 kg,800 mg daily in patients weighing >60 and ≤80 kg, and1000 mg daily in patients with a body weight of >80 kg). Based on the treatment duration, patients would be randomized in either of the 3 treatment groups - Group 1 - Sofosbuvir + Ribavirin x 24 weeks Group 2 - Sofosbuvir + Ribavirin x 36 weeks Group 3 - Sofosbuvir + Ribavirin x 48 weeks

Official Title
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To Evaluate the Safety and Efficacy of Sofosbuvir and Ribavirin in Patients With HCV (Genotype 3) Related Decompensated Cirrhosis - A Randomized Open- Label Study

Conditions
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HCV Related Cirrhosis

Intervention / Treatment
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* Drug: Sofosbuvir + Ribavirin 1
* Drug: Sofosbuvir + Ribavirin 2
* Drug: Sofosbuvir + Ribavirin 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female ≥ 18 yrs Baseline HCV RNA > 1000 IU/ml Cirrhosis with current or prior decompensation HCV (Hepatitis C Infection) Genotype 3 Treatment naïve or treatment experienced Exclusion Criteria: HIV or HBV (Hepatitis B Virus) co-infection Recent Variceal bleed Pregnancy Haemolytic anaemia Platelet counts <20,000/ml Advanced HCC (Hepatocellular Carcinoma) Renal dysfunction, GFR (glomerular filtration rate) < 30 ml/min Haemoglobin < 10 g/dl MELD (Model for End Stage Liver Disease) >25, CTP (Child-Turcotte-Pugh score) >12 Post organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sofosbuvir + Ribavirin 1<br>Sofosbuvir + Ribavirin x 24 weeks | Drug: Sofosbuvir + Ribavirin 1<br> <br> |
| Experimental: Sofosbuvir + Ribavirin 2<br>Sofosbuvir + Ribavirin x 36 weeks | Drug: Sofosbuvir + Ribavirin 2<br> <br> |
| Experimental: Sofosbuvir + Ribavirin 3<br>Sofosbuvir + Ribavirin x 48 weeks | Drug: Sofosbuvir + Ribavirin 3<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary efficacy end point is SVR 24 defined as HCV RNA <LLOQ (lower limit of quantification) |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary endpoint is any AE (Adverse Event) leading to permanent discontinuation of study drugs. |  | 3 years | 
| Mortality at 6 months post therapy in all the 3 groups. |  | 48 weeks | 
| Improvement in the liver function as determined by CTP (Child-Turcotte-Pugh score), MELD (Model for End Stage liver Disease)more than 2 points at 6 months and 1 year. |  | 48 weeks | 
| Number of new cases of Hepatocellular Carcinoma at end of therapy and at 6 months post therapy in all the 3 groups. |  | 48 weeks | 
| Reduction in HVPG >20% to baseline after 1 year in all the 3 groups. |  | 48 weeks | 
| SVR 4 defined as HCV RNA <LLOQ (lower limit of quantification) |  | 24 weeks | 
| SVR 12 defined as HCV RNA <LLOQ (lower limit of quantification) |  | 36 weeks |