Boceprevir Treatment in Liver Pre-transplant HCV Patients
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation(LT) worldwide (30~40%). Within 5 years, about 25-30% of liver transplant recipients with recurrent hepatitis C would progress to liver cirrhosis (Ponziani et. Al, 2011), it also accounts for 2/3 of graft failure and deaths after liver transplantation.(Bzowej et al., 2011)
Kaohsiung Chang Gung Memorial Hospital continue to have at least 45 HCV-related liver disease patients awaiting for liver transplantation annually. If the HCV viral load can be significantly reduced or sustained virologic response (SVR) can be achieved by triple therapy with Pegylated interferon alfa(PEG)/Ribavirin(RBV)/Boceprevir(BOC) treatment before liver transplantation(LT), the graft re-infection of HCV can be prevented. By this way, we can reduce the risk of early fibrosis progression in the liver graft, and hopefully, improving graft and patient survival after liver transplantation.(Toniutto, 2008)(Ponziani et al, 2011).
We aim to conduct an prospective, open label, single arm study. This study design is single arm to treat HCV patients with Pegylated interferon alfa(PEG)/Ribavirin(RBV)/Boceprevir(BOC) triple therapies before liver transplantation for patients with detectable HCV RNA. The total number of patients would be around 20 cases included in the study and all of them will take Pegylated interferon alfa(PEG)/Ribavirin(RBV)/Boceprevir(BOC) triple therapy. The experimental regimen contains 4 week lead-in therapy with Peg-Interferon α-2b plus Ribavirin. Then after, triple therapy with Boceprevir + Peg-Interferon α-2b + Ribavirin will be used for at least 16 weeks or maximal 44 weeks before transplantation. Normal practice based on the treatment protocol of the Kaohsiung Chang Gung Memorial Hospital liver transplant center will be done before enrollment. Patients will be monitored for all the efficacy and safety endpoints during the treatment period. HCV RNA will be checked at time of transplant. Finally, patients will received regular monitoring of HCV RNA 1, 3, 6, 9, 12 months after liver transplantation.
详细描述
End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation(LT) worldwide (30~40%). Within 5 years, about 25-30% of liver transplant recipients with recurrent hepatitis C would progress to liver cirrhosis (Ponziani et. Al, 2011), it also accounts for 2/3 of graft failure and deaths after liver transplantation.(Bzowej et al., 2011)
Kaohsiung Chang Gung Memorial Hospital continue to have at least 45 HCV-related liver disease patients awaiting for liver transplantation annually. If the HCV viral load can be significantly reduced or sustained virologic response (SVR) can be achieved by triple therapy with pegylated interferon alfa (PEG)/Ribavirin(RBV)/Boceprevir(BOC) treatment before liver transplantation(LT), the graft re-infection of HCV can be prevented. By this way, we can reduce the risk of early fibrosis progression in the liver graft, and hopefully, improving graft and patient survival after liver transplantation.(Toniutto, 2008)(Ponziani et al, 2011).
We aim to conduct a prospective, open label, single arm study. This study design is single arm to treat HCV patients with pegylated interferon alfa (PEG)/Ribavirin(RBV)/Boceprevir(BOC) triple therapies before liver transplantation for patients with detectable HCV RNA. The total number of patients would be around 20 cases included in the study and all of them will take pegylated interferon alfa (PEG)/Ribavirin(RBV)/Boceprevir(BOC) triple therapy. The experimental regimen contains 4 week lead-in therapy with Peg-Interferon α-2b plus Ribavirin, followed by Boceprevir + Peg-Interferon α-2b + Ribavirin for at least 16 weeks or maximal 44 weeks before transplantation. The treatment will be discontinued immediately at time of liver transplantation. Normal practice based on the treatment protocol of the Kaohsiung Chang Gung Memorial Hospital liver transplant center will be done before enrollment.
-Treatment Stopping Rules-
If the patient has HCV RNA >100 IU/ml at week 12 after the beginning of treatment with peg interferon plus ribavirin, i.e. 8 weeks after the initiation of therapy with boceprevir, all HCV medications are to be discontinued.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult 20 years and older
- •Chronic infection with genotype 1 hepatitis C virus proven with positive PCR
- •Liver cirrhosis while awaiting liver transplantation
- •Patient with compensated liver functions
- •With or without hepatocellular carcinoma.
- •Naive or experienced (failure) to HCV antiviral treatmentFailure is defined according to the following terminology:
- •Relapsing patient: HCV RNA undetectable at the end of treatment, becoming detectable again after the discontinuation of treatment
- •Breakthrough: increase of viremia of 1 log or more during the treatment
- •Non-responding patient with partial response: HCV RNA detectable at W24 without ever having been undetectable and with a decrease in HCV RNA ≥ 2 log at W12
- •Non-responding patient with null response: decrease in HCV RNA < 2 log at W12
- •No need for prior treatment wash-out
- •Written patient informed consent
排除标准
- •Non controlled sepsis
- •Platelets < 50,000/mm3
- •Neutrophil granulocyte levels < 1000/mm3
- •Creatinine clearance < 50 mL/min
- •Hb < 10 g/dL
- •Uncontrolled psychiatric problems
- •Hypersensitivity or contraindications to any component of boceprevir formulation
- •Contraindication to interferon or ribavirin
- •HIV coinfection
- •HBV coinfection (unless this is treated effectively with analogues, as proven by undetectable viremia for at least 12 months)
- •Other infectious disease underway
- •Neoplastic disease other than hepatocellular carcinoma during the previous year, or neoplastic disease for which the prognosis is less than 3 years
- •Treatment with immunosuppressors (including corticosteroids), antivirals other than those for the study, except aciclovir
- •Current or anticipated use of any of the following prohibited medications: midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives
- •Person participating in another study including an exclusion period that is still underway during pre-enrollment
- •Pregnancy, breast-feeding
研究组 & 干预措施
Boc+Peg-int alfa+Rbv
Boceprevir 800mg/TID+Pegylated interferon alfa+Ribavirin
干预措施: Boceprevir 800mg/TID+Pegylated interferon alfa+Ribavirin (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: within 1 year
次要结局
- HCV-RNA (Hepatitis C virus RNA) level(within 1 year)
研究者
Hu Tsung-Hui
Tsung-Hui Hu MD.PhD
Chang Gung Memorial Hospital