An Unicenter, Prospective, Randomized, Pilot Study Comparing the Effect of Everolimus-containing Versus mTOR Inhibitor Free Immunosuppression in the Evolution of Hepatitis C Fibrosis After Liver Transplantation.
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- To compare the liver fibrosis progression (F≥2 under ISHAK score) in patients who receive everolimus vs mTOR free immunosuppression
Study Overview
Brief Summary
Background:
Hepatitis C recurrence, which invariably occurs in viremic liver transplant (LT) recipients, associated with accelerated liver fibrosis leading to established graft cirrhosis in 40-20% of patients in 5 years with another 5% experiencing an aggressive form with cirrhosis and graft loss in 1 year. Since treatment after LT has a low efficacy, the overall survival of HCV-infected LT recipients is shorter than that of uninfected LT patients.
New immunosuppressive agents such as mTOR inhibitors (Everolimus/Sirolimus) reduce the risk of liver graft rejection, have antifibrotic properties and do not worsen HCV recurrence. Moreover new directly-acting antiviral agents have increased efficacy of interferon-based treatment but their use in LT recipients may be limited by side effects.
Hypothesis:
Use of individualized immunosuppressive regimen and early personalized anti-viral treatment based on recipient and viral factors would improve outcome of HCV infected liver transplant recipients.
Objectives:
- To evaluate safety and efficacy of two steroid-free immunosuppressive regimens to reduce hepatitis C recurrence associated to fibrosis progression (F≥2 under ISHAK score) at one year post-transplant.
- To identify viral and recipient factors associated with liver fibrosis progression using ultra-deep pyrosequencing (UDPS).
Detailed Description
Study design:
A pilot, open-label, prospective, randomized and unicenter study. As pilot study, the number of patients expected to be included is n=40.
Inclusion criteria:
- Age≥18 years
- First liver transplant
- RNA-HCV positive within 12 months previous to the transplant
Exclusion criteria:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 68 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age≥18 years
- •First liver transplant
- •RNA-HCV positive within 12 months previous to the transplant
Exclusion Criteria
- •Multiorgan transplant
- •Split liver
- •Fulminant hepatitis
- •ABO incompatible
- •HIV positive patients
- •Glomerular Filtration rate ≤60mL/min/1.73m2
Arms & Interventions
MMF arm
MMF arm (n=20)
They will receive immunosuppression as stipulated by hospital protocol:
Tacrolimus (levels 8-10ng/mL) and Mycophenalate mofetil 1mg bid(levels 1-3ng/mL).
Intervention: MMF arm (Drug)
EVL arm
EVL arm (n=20):
Tacrolimus (levels 8-10ng/ml) + everolimus 1mg bid (levels 2-4 ng/mL)
Intervention: EVL arm (Drug)
Outcomes
Primary Outcomes
To compare the liver fibrosis progression (F≥2 under ISHAK score) in patients who receive everolimus vs mTOR free immunosuppression
Time Frame: One year
Liver biopsy will be performed at 12th months post-transplant. All biopsy specimens will be read by a single pathologist. Necroinflammatory activity and fibrosis stage were scored using ISHAK classification.
Secondary Outcomes
- To identify viral and recipient molecular predictors of fibrosis and anti-HCV treatment responses in liver transplant recipients under steroid-free immunosuppression(Immediately before liver transplantation, in the anhepatic phase, at the beginning and at the end of the reperfusion, and at 1h, 4h, 8h, 12h, 18h, 1dy, 3dy, 7dy, 14dy, 28dy, 2mo, 3mo, 6mo, 9mo and 12mo post-transplant)
Investigators
Cristina Dopazo Taboada
Liver Surgery and Transplants Consultant, PhD/MD
Hospital Vall d'Hebron