A Pilot Study on the Efficicay and Safety of Pegylated Interferon, Ribavirin and Telaprevir in Recurrent Hepatitis C Virus (HCV) Infection in Orthotopic Liver Transplant (OLT) Recipients.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- The Efficacy of Triple Antiviral Therapy
研究概览
简要总结
Patients are being asked to be part of this study because they are a liver transplant recipient and have the Hepatitis C Virus (HCV). Current routine treatment for HCV for liver transplant patients includes taking two medications called pegylated interferon alfa-2a (Pegasys®) and ribavirin. Patients Pegasys and ribavirin are FDA approved for the treatment of HCV.
This study will evaluate the safety and efficacy of adding a third drug called telaprevir for the experimental treatment of HCV in liver transplant patients. The combination of Pegasys, ribavirin and telaprevir is currently FDA approved for the treatment of HCV, but is specifically not FDA approved for HCV patients who have had a liver transplant. This is because more information is needed about possible drug interactions between telaprevir and cyclosporine, or telaprevir and tacrolimus-based immunosuppressive drugs, which are typically part of routine care for transplant patients.
Studies have shown that the addition of telaprevir greatly increases the efficacy of Pegasys and ribavirin for the treatment of HCV. However, these studies did not include adequate information on transplant patients due to the potential drug interactions.
The investigators hope to gather more information about the safety and efficacy of telaprevir given in combination with Pegasys and ribavirin in the liver transplant patients who have HCV that is not well controlled with Pegasys and ribavirin alone.
详细描述
BACKGROUND:
Cirrhosis from HCV is the most common indication for OLT. Unfortunately, disease recurrence in the allograft is virtually universal. The spectrum of disease recurrence ranges from minimal inflammation to severe cholestasis as well as cirrhosis, leading to allograft failure. Previous reports indicated a comparable survival rate between patients who received OLT for HCV and those who received OLT for other indications. More recent data, however, suggested that HCV-positive recipients have significantly impaired patient and allograft survival following OLT as compared to HCV-negative recipients. Approximately 20% of patients with recurrent HCV have cirrhosis at 5 years post-OLT.
Attempts to treat HCV recurrence in OLT recipients have had limited success. Sustained virologic responses (SVR) have only been seen in up to 30% of patients with genotype 1 infection, whereas SVR has been higher at 42-46% for non-transplant counterparts. Most recently, the addition of telaprevir to pegylated interferon and ribavirin to comprise the triple therapy in the nontransplant HCV-infected population has led to significantly higher sustained virologic response rate (SVR) of 75% when compared to 44% observed in the control arm which received pegylated interferon and ribavirin. Its side effect profile was acceptable to allow the FDA to approve the drug on May 23, 2011. However, there is no data on the efficacy and safety of telaprevir in OLT recipients. In fact, its use in this population is greatly hindered by a significant drug-drug interaction with the major immunosuppressive agents used in OLT, namely tacrolimus and cyclosporine. Telaprevir increases cyslosporine exposure by 4.6 fold and its half-life by 3.5 fold. It increases tacrolimus exposure to 70 fold and its half-life by 4.9 fold. Clearly, the doses of these immunosuppressive agents need to be adjusted at the start and end of telaprevir therapy.
The primary aim of our study is to determine the safety and efficacy of pegylated interferon alfa-2a (Pegasys®), ribavirin, and telaprevir therapy in liver transplant recipients with hepatitis C recurrence who are maintained on cyclosporine or tacrolimus-based immunosuppression. We hypothesize that triple therapy will have better sustained virologic response rates than the current standard of care, pegylated interferon and ribavirin, with an acceptable side-effect profile.
STUDY DESIGN:
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
- •Male or female patients > 18 years of age.
- •Detectable plasma HCV-RNA by qualitative PCR assay.
- •HCV genotype 1 infection,
- •Documented recurrent hepatitis C by liver biopsy within the past year.
- •On cyclosporine or tacrolimus-based immunosuppression
- •Negative urine pregnancy test before initiating the treatment for women of childbearing potential.
- •Willingness of the patient and all potentially childbearing partners to use a reliable form of effective contraception during the study, unless the patient or partner is surgically sterile or post-menopausal.
- •Willingness to undergo provide informed consent and comply with study requirements.
排除标准
- •Genotype non-1 HCV infection.
- •Women who are pregnant or breast-feeding.
- •Male partners of women who are pregnant.
- •Evidence of co-infection with HIV or hepatitis B.
- •History of severe psychiatric disease.
- •History of immunologically mediated disease (e.g., inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, etc.)
- •History of clinically significant pulmonary disease.
- •History of severe cardiac disease.
- •History of malignancy where risk of recurrence is >20% within 2 years.
- •History of uncontrolled seizure disorder.
- •History of poorly controlled thyroid disease.
- •History of poorly controlled diabetes mellitus.
- •History of severe retinopathy.
- •Active gout.
- •History or evidence of severe medical illness that, in the opinion of the investigator, makes the patient unsuitable for pegylated interferon alfa-2a treatment (Pegasys®).
- •Inability or unwillingness to abstain from alcohol throughout the entire study period.
研究组 & 干预措施
HCV, LT, Pegasys, ribavirin, telaprevir
Patients are being asked to be part of this arm because they are orthotopic liver transplant recipients (OLT) and have the Hepatitis C Virus (HCV). They will be given the study drugs Pegasys, ribavirin and telaprevir
干预措施: Peginterferon alfa-2a (Drug)
HCV, LT, Pegasys, ribavirin, telaprevir
Patients are being asked to be part of this arm because they are orthotopic liver transplant recipients (OLT) and have the Hepatitis C Virus (HCV). They will be given the study drugs Pegasys, ribavirin and telaprevir
干预措施: Ribavirin (Drug)
HCV, LT, Pegasys, ribavirin, telaprevir
Patients are being asked to be part of this arm because they are orthotopic liver transplant recipients (OLT) and have the Hepatitis C Virus (HCV). They will be given the study drugs Pegasys, ribavirin and telaprevir
干预措施: telaprevir (Drug)
结局指标
主要结局
The Efficacy of Triple Antiviral Therapy
时间窗: 3 years from start of study
To evaluate the efficacy of triple antiviral therapy, consisting of pegylated interferon alfa-2a (Pegasys®), ribavirin, and telaprevir therapy in liver transplant recipients with hepatitis C. This will be measured and reported by sustained virologic response (defined as undetectable HCV RNA in the blood 24 weeks after completing therapy \[SVR24\])
次要结局
- Safety of Triple Antiviral Therapy in HCV Infected OLT Recipients(6 years from the start of the study)