Efficacy of High Doses of Both Pegylated Interferon Alfa-2a and Ribavirin for Retreatment of HIV-coinfected Patients With Liver Cirrhosis Due to HCV Genotype 1 or 4 Nonresponders to Previous Standard Therapy.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 4
- 主要终点
- Sustained viral response (undetectable serum HCV-RNA)
研究概览
简要总结
Objective: To evaluate the efficacy and safety of high doses of both peginterferon-alfa 2a (360 ug per week) plus ribavirin (800 mg b.i.d.) in HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(*) to a standard dose treatment of both drugs.
(*) Non previous virological response: no decrease of plasma RNA-HCV at least 2 log10 after 12 weeks in treatment or breakthrough viremia while on treatment.
Additionally, this study will evaluated the influence of simultaneous peginterferon-alfa 2a and ribavirin plasma concentrations on early viral response (EVR) and sustained viral response (SVR) in these patients.
Method: Pilot clinical trial, phase II-III, open labeled multicenter in which patients from several hospitals of the Servicio Andaluz de Salud will be enrolled.
The usual clinical and analytical follow up will be performed but additional blood samples will be obtained for determination of interferon and ribavirin plasma levels. The primary end point will be a sustained virologic response (defined as an undetectable serum HCV-RNA after 24 weeks after the cessation of treatment). Likewise, rapid virological response (at 4 weeks of treatment), early virological response (at 12 weeks), and end of treatment response rates will be evaluated as well as their relationships with the plasma interferon an ribavirin concentrations determined by ELISA and HPLC, respectively. The safety and tolerability of the studied medications will be evaluated by means of clinical adverse events, physical examination and laboratory results. The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age older than 18 years
- •HIV-infected patients with compensated liver cirrhosis by HCV genotype 1 or 4 without previous virological response(*) to a standard dose treatment of both drugs.
- •Women of child-bearing age: negative pregnancy test
- •Ability to understand and sign a written consent form
排除标准
- •HCV genotypes different to 1 or 4
- •Acute or chronic hepatitis B infection (positivity for hepatitis B surface antigen or plasma DNA) or other concomitant causes of liver disease
- •Pregnancy or breast feeding.
- •Decompensated liver disease at baseline.
- •Neutropenia <1000/uL, anemia <100 g/L or thrombocytopenia <20.000/uL.
- •Creatinine clearance < 50 mL/min.
- •Concomitant treatment with immunomodulators or zidovudine, didanosine or stavudine.
- •Organ or bone marrow transplantation
- •Current alcoholism or iv drug abuse. Methadone is allowed.
- •Current neoplasm and/or anti-tumor chemotherapy or immunomodulators
- •Psychosis or uncontrolled clinical depression
- •Auto-immune disease, including auto-immune hepatitis
- •History of significant cardiovascular disease (NYHA III-IV) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure.
- •Thyroid dysfunction.
- •Clinically significant retinal abnormalities
- •Inability to understand and sign a written consent form
研究组 & 干预措施
PegIFN alfa-2a and Ribavirin
HIV-coinfected patients with compensated cirrhosis by hepatitis C virus, genotype 1 or 4.
干预措施: Pegylated interferon alfa-2a and Ribavirin (Drug)
结局指标
主要结局
Sustained viral response (undetectable serum HCV-RNA)
时间窗: Throughout treatment and 24 weeks after finishing it
次要结局
- Relationships between the plasma interferon an ribavirin concentrations and efficacy(Throughout treatment and 24 weeks after finishing it.)
- safety and tolerability of the studied medications(Throughout treatment and 24 weeks after finishing it)
- The evolution of liver fibrosis will be evaluated comparing the basal and end of treatment results of transient elastometry(baseline and after finishing treatment)
研究者
Antonio Rivero
Luis Fernando Lopez-Cortes
Sociedad Andaluza de Enfermedades Infecciosas