Prospective, Open-label, Single Arm Pilot Study Evaluating the Effect on Virological Response of the Switch From Tacrolimus to Cyclosporin Associated With a Peginterferon Alfa-2a / Ribavirin Bitherapy, in Non-responder or With Recurrent VHC+ Disease Liver Transplanted Patients.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 13
- 主要终点
- Prolonged virological response
研究概览
简要总结
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation and recurrence causes chronic liver disease in 50 to 80% of cases. The aim of this study is to assess the efficacy of cyclosporin on C virological response. Patients included in the Transpeg 1 study and non-responder or with a recurrent disease will be switched from their tacrolimus therapy to cyclosporin, in association with a 1 year peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.
详细描述
In France, 50% of hepatitis C virus carriers develop chronic clinical hepatitis, which may lead to cirrhosis and liver transplantation. Transplant infection by hepatitis C virus is constant after transplantation. A main factor determining the severity of recurrent hepatitis C after transplantation may be immunosuppression. Thus optimization of immunosuppressive regimens might be a key aspect to improve the prognosis of chronic hepatitis C in transplanted patients. The two most frequently used immunosuppressive drugs are cyclosporin and tacrolimus. However, it has been shown that virus replication could be inhibited by cyclosporin, through the blockade of cyclophilins, decreasing hepatitis C viral load and improving liver function. These effects were not found with tacrolimus.
The aim of our study is to assess the efficacy on C virological response of the switch from tacrolimus to cyclosporin associated with a peginterferon alfa-2a / ribavirin bitherapy, in non-responder or with a recurrent VHC+ disease liver transplanted patients.
Patients will receive a 19 month cyclosporin treatment, associated during 12 months with a peginterferon alfa-2a / ribavirin bitherapy. Efficacy will be assessed by the percentage of patients with a negative qualitative PCR after 19 months of cyclosporin treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Adults aged 18 or over,
- •Who had been included in the Transpeg 1 study,
- •Non-responders after a three month peginterferon alfa-2a / ribavirin bitherapy or with a recurrent disease during the Transpeg 1 maintenance phase, whatever the randomization group (ribavirin or placebo),
- •With a positive qualitative PCR at inclusion,
- •With a METAVIR histologic score of 1 or more on the last biopsy (done within the 6 months preceding inclusion),
- •Treated with tacrolimus for at least 6 months prior to inclusion,
- •Having given a written informed consent.
排除标准
- •Treatment with peginterferon or ribavirin within the 6 months preceding inclusion,
- •Severe hepatocellular failure or decompensated cirrhosis,
- •Acute graft rejection within the two months preceding inclusion, or signs of chronic rejection on the last biopsy, or retransplantation since inclusion in the Transpeg 1 study,
- •Treatment with cyclosporin for more than 6 months during the 24 months preceding inclusion,
- •Treatment with a mTOR inhibitor or with another investigational immunosuppressive drug,
- •Positive serology for HIV or HBV,
- •Cancer (or history of other malignancy during the last 5 years) except patients transplanted for hepatocellular carcinoma and basocellular or excised spinocellular carcinoma,
- •Serious concomitant disease or acute or chronic disorder, other than the current transplant, treated with steroids,
- •Serious cardiac pathology within the last 6 months,
- •Women with ongoing pregnancy or breast-feeding,
- •Serious chronic renal failure (creatinine clearance < 30 ml/mn),
- •Haemoglobin < 10 g/dl, platelets < 50 000/mm3 or neutrophils < 1000 / mm3,
- •Abnormal TSH values,
- •Inability to cooperate or to communicate with the investigator,
- •Contraindications to ribavirin, peginterferon alfa-2a or cyclosporin.
研究组 & 干预措施
Ciclosporin
干预措施: ciclosporin (Drug)
结局指标
主要结局
Prolonged virological response
时间窗: 19 months
Percentage of patients with a negative qualitative PCR, 19 months after the initiation of cyclosporin treatment.
次要结局
- Virological response 4, 7 and 13 months after the initiation of cyclosporin treatment(4, 7 and 13 months)
- Histological response: METAVIR score at 19 months(19 months)
- Biological response: liver function at 4, 7, 13 and 19 months(4, 7, 13 and 19 months)
- Incidence of acute or chronic graft rejection at 19 months(19 months)
- Incidence of death, graft loss and retransplantation at 13 and 19 months(13 and 19 months)
- Renal function at 4, 7, 13 and 19 months(4, 7, 13 and 19 months)
- Incidence of treatment discontinuation at 4, 7, 13 and 19 months(4, 7, 13 and 19 months)
- Incidence of adverse events (cancers in particular).(19 months)