Legalon SIL for the Treatment of HCV Recurrence in Liver Transplanted Patients
Orthotopic liver transplantation (OLT) is the treatment of choice for patients with Hepatitis C Virus (HCV) infection and end-stage liver disease or hepatocellular carcinoma; infection of the graft and hepatitis C recurrence is universal after OLT and recurrent HCV hepatitis often follows an accelerated course after OLT, with rapid histological recurrence and cirrhosis. These very poor outcome significantly affect graft and patient survival and reduces the benefit of transplantation for this indication. Therapeutic strategies are not available; high viral load, high prevalence of genotype 1b and need of dose reduction of interferon and ribavirin because of the side effects or intolerance, together with the interference of immunosuppressive drugs, resulted in the vast majority of the patients in failure in obtaining viral eradication.
Recently, Silibinin, has been studied and reported to be capable to act as potent antiviral agent in patients with HCV; it has been used successfully in a protocol of a 14 day intravenous infusion in previous non-responders to peginterferon/ribavirin therapy. In view of his postulated profile of safety, it seems an ideal drug to be used in the setting of HCV recurrent patients after liver transplant.
Aim of this prospective, randomized, double-blind, placebo-controlled, parallel group study is to determine the therapeutic effect of Legalon SIL in the prevention of HCV reinfection in chronically infected hepatitis C patients after OLT.
Awaiting orthotopic liver transplantation patients affected by HCV will be randomised 3:1 to receive, in addition to their current therapy, silibinin 20mg/kg/day (Legalon SIL) or placebo infused over 2 hours from 14 to 21 consecutive days; in addition, patients will receive treatment with silibinin 20mg/kg/day (Legalon SIL), infused over 2 hours, for 7 days after transplant.
The Primary Efficacy endpoint is to achieve sustained virological response (SVR) while Secondary Efficacy endpoints are to evaluate the virologic response, the percentage of patients who has a decreased of at least 2 log10 the levels of HCV-RNA and the safety of Legalon SIL in this population.
|HCV Recurrence After Liver Transplantation||Drug: Silibinin Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind, Placebo Controlled Study to Investigate the Efficacy and Safety of Legalon SIL for the Treatment of HCV Recurrence of the Graft in Orthotopic Liver Transplant Patients|
- Sustained virological response (SVR), defined as Virological Response (undetectable HCV-RNA) that lasts 6 months after the transplant [ Time Frame: 6 months ]
- Virologic response (VR) defined as undetectable HCV RNA [ Time Frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT ]
- Percentage of patients who has a decreased of at least 2 log10 the levels of HCV-RNA [ Time Frame: at week 4 after OLT ]
- Number of patients with AE [ Time Frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT ]
- laboratory parameters [ Time Frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT ]
- blood levels of immunosuppressive drugs [ Time Frame: week 1, 2, 3, 4, 8, 12, 24 after OLT ]
- Vital signs [ Time Frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT ]
- ECG [ Time Frame: after 14-21 days of pre-OLT and 7 days of post-OLT treatment; week 2, 3, 4, 8, 12, 24 after OLT ]
|Study Start Date:||September 2010|
|Study Completion Date:||November 2011|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Silibinin 20mg/Kg/day (Legalon SIL) by intravenous infusion for 14-21 days before OLT and for 7 days after OLT
20mg/Kg daily by intravenous infusion, for 14-21 days pre-OLT and for 7 days post-OLT
Other Name: Legalon SIL
Placebo Comparator: Placebo
Placebo (NaCl 0.9% - saline) administered daily by intravenous infusion for 14-21 days before OLT and 7 days after OLT
Saline, daily infused for 14-21 days pre-OLT and for 7 days post-OLT
Please refer to this study by its ClinicalTrials.gov identifier: NCT01535092
|Principal Investigator:||Xavier Forns, Dr||Hospital Clinic i Barcelona|