Directly Observed Therapy for the Delivery of HCV Therapy Among HCV-infected Individuals in Chennai, India
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- HCV Treatment Completion
研究概览
简要总结
The primary objective of this pilot trial is to evaluate the feasibility of 12 weeks vs. 24 weeks of field-based directly observed therapy (DOT) for HCV therapy in a resource-limited setting. The investigators will compare treatment completion rates among 50 persons chronically infected with HCV who will be randomized to receive either 1) 12 weeks of sofosbuvir (SOF) + ribavirin (RBV) + pegylated interferon alfa-2a (PEG); or 2) 24 weeks of SOF + RBV. Treatment will be delivered daily by field workers at a location of a participants choosing. Secondary objectives are 1) To compare the efficacy of SOF+RBV with or without PEG as measured by the proportion of subjects with sustained viral response at 12 weeks after discontinuation of therapy (SVR12); 2) To evaluate the safety and tolerability of SOF+RBV with or without PEG; 3) To assess the impact of SVR12 on insulin resistance.
详细描述
This will be a non-blinded randomized clinical trial with 50 participants randomized at a 1:1 allocation ratio to one of two treatment arms.
Arm 1: Sofosbuvir (400mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) + Ribavirin (800mg/daily) for 12 weeks
Arm 2: Sofosbuvir (400mg/daily) + Ribavirin (800mg/daily) for 24 weeks
Pegylated-interferon alfa-2a (PEG) will be delivered subcutaneously once weekly. Sofosbuvir (SOF) and ribavirin (RBV) will be taken orally once daily for the entire study period.
The study will take place at the YR Gaitonde Centre for AIDS Research and Education (YRGCARE). YRG CARE is a non-profit medical and research institution in Chennai. YRGCARE Medical Centre provides medical care for more than 18,000 persons with HIV disease. Currently more than 8000 persons are receiving highly active antiretroviral therapy at the center.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing/able to provide consent
- •Chronic HCV (HCV RNA positive)
- •Resident of Chennai and can provide locator information
- •If co-infected with HIV, must have CD4 (Cluster of Differentation 4) > 350 cells/mm3 and either: 1) ART naïve or 2) if on ART be on a tenofovir-containing regimen. If a participant's CD4 drops below 350 cells/μl (threshold for treatment in India), will have to initiate a tenofovir-containing regimen (current standard of care).
- •Participants must have the following at screening:
- •Alanine Aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)
- •Aspartate Aminotransferase (AST) ≤ 10 x ULN
- •Hemoglobin ≥ 12 g/dl for males and 11 g/dl for females
- •International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
- •Albumin ≥ 3 g/dl
- •Direct bilirubin ≤ 1.5 x ULN
- •Creatinine clearance ≥ 60 ml/min (Cockgroft-Gault Equation)
- •Alpha fetoprotein < 50 ng/ml
- •Absolute neutrophil count (ANC) ≥ 1,500/μL
- •Platelets ≥ 90,000/μL
- •Thyroid stimulating hormone (TSH) ≤ ULN
- •A female subject is eligible if it is confirmed that she is:
- •Not pregnant or nursing
- •Of non-childbearing potential (i.e., women who have had hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 50 years of age with cessation (for ≥12 months) of previously occurring menses
- •Of childbearing potential and negative urine pregnancy test prior to randomization and agree to one of the following from 3 weeks prior to Baseline/Day 1 until 6 months after the last dose of RBV.
- •Complete abstinence from intercourse.
- •Consistent use of approved methods of birth control in addition to a male partner who correctly uses a condom from 3 weeks prior to Baseline/Day 1 until 6 months after the last dose of RBV.
- •Male participants must agree to consistently and correctly use a condom. If their female partner is of childbearing potential, their partner must agree to use one of the study approved non-hormonal methods of birth control or a hormone-containing contraceptive, from the date of screening until 7 months after their last dose of RBV
- •Male participants must agree to refrain from sperm donation for at least 7 months after the last dose of RBV.
- •Of generally good health as determined by the investigator.
- •Able to comply with the dosing instructions for study drug administration and willing to complete the study schedule of assessments.
排除标准
- •Pregnant/nursing female or male with pregnant/nursing female partner.
- •Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage, MELD<12)
- •Prior hepatitis C treatment
- •Infection with hepatitis B virus
- •Chronic use of systematically administered immunosuppressive agents (e.g., prednisone equivalent >10 mg/day)
- •Use of any prohibited concomitant medications within 28 days of the Baseline/Day 1 visit.
- •Contraindications to RBV therapy or PEG/RBV
- •Known hypersensitivity to RBV or PEG, the metabolites or formulation excipients
- •Additional exclusion criteria related to Aim 1 regimen
- •Pre-existing significant psychiatric condition(s) including severe depression, severe bipolar disorder and schizophrenia. Other psychiatric disorders are permitted if the condition is well controlled with a stable treatment regimen for ≥ 1 year from screening.
- •Presence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis).
- •History of clinical significant retinal disease.
研究组 & 干预措施
SOF+RBV
Sofosbuvir (400mg/daily) + Ribavirin (800mg/daily) for 24 weeks
干预措施: Ribavirin (Drug)
SOF+PEG+RBV
Sofosbuvir (400mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) + Ribavirin (800mg/daily) for 12 weeks
干预措施: Ribavirin (Drug)
SOF+RBV
Sofosbuvir (400mg/daily) + Ribavirin (800mg/daily) for 24 weeks
干预措施: Sofosbuvir (Drug)
SOF+PEG+RBV
Sofosbuvir (400mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) + Ribavirin (800mg/daily) for 12 weeks
干预措施: Pegylated Interferon alfa-2a (Drug)
SOF+PEG+RBV
Sofosbuvir (400mg/daily) + Pegylated Interferon alfa-2a (180µg/weekly) + Ribavirin (800mg/daily) for 12 weeks
干预措施: Sofosbuvir (Drug)
结局指标
主要结局
HCV Treatment Completion
时间窗: 12 weeks from baseline for SOF+PEG+RBV and 24 weeks from baselne for SOF+RBV
The percentage of subjects that complete their course of treatment
次要结局
- Serious Adverse Events(24 weeks from baseline SOF+PEG+RBV and 36 weeks from baseline for SOF+RBV)
- Sustained Virologic Response (SVR)(24 weeks from baseline for SOF+PEG+RBV and 36 weeks from baseline for SOF+RBV)
- Change in Insulin Resistance(Difference from entry to 24 weeks for SOF+PEG+RBV and difference from entry to 36 weeks for SOF+RBV)