Hepatitis C Recurrence After Liver Transplant Clinical Trial
Official title:
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.
| Verified date | August 2016 |
| Source | Hospital Vall d'Hebron |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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:
1. 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.
2. To identify viral and recipient factors associated with liver fibrosis progression using
ultra-deep pyrosequencing (UDPS).
| Status | Completed |
| Enrollment | 18 |
| Est. completion date | August 2016 |
| Est. primary completion date | August 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 68 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Spain | Department of HPB Surgery and Transplant, Hospital Vall d´Hebron | Barcelona |
| Lead Sponsor | Collaborator |
|---|---|
| Hospital Vall d'Hebron |
Spain,
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* Note: There are 23 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | To analyze liver fibrosis progression using serum markers | Serum samples will be taken from peripheral circulation an frozen at -21ºC. Serum markers (HA, PIIINP, and TIMP-1) are analyzed by a fully automated, two-site sandwich immunoassay using direct chemiluminometric technology (ADVIA Centayr XP, Siemens Healthcare Diagnositics). The algorithm including the three markers (3-M-ALG) {score= -7,412 + [ln (HA)x0,681] + [ln (PIIINP)x0.775] + [ln (TIMP-1)]x0,494} will be also obtained. | 3rd, 6th and 12th months post-transplant | |
| Other | To analyze liver fibrosis progression using liver stiffness | Transient elastography (FibroScan) for liver stiffness measurements will be performed in clinics. | 6th and 12th months post-transplant | |
| Other | To analyze the incidence of acute rejection and steroid-resistant acute rejection | Rejection will be suspected in patients with an increase in the levels of bilirrubin, transaminases or alkaline phosphatase. Doppler ultrasound will be performed in order to discard biliary dilation and to confirm portal and arterial flow patency. A liver biopsy will be performed and graft rejection will be defined and stratified according to the BANFF criteria. | 6th and 12th months post-transplant | |
| Other | To analyze the timing to the first acute rejection episode in both study groups | 6th and 12 months post-transplant | ||
| Other | To analyze need of antiviral therapy at the end of the first year post-transplant | Antiviral treatment will be considered at the end of the 12-months study period if moderated fibrosis (F=2 under ISHAK score)is diagnosed and the patient do not have any contraindications to therapy | One year post-transplant | |
| Other | To analyze graft and patient survival | One year post-transplant | ||
| Other | To analyze the incidence of patient withdrawal | One year post-transplant | ||
| Other | To analyze the incidence of cardiovascular risk factors | Cardiovascular risk factors will be defined as follow: Arterial hypertension. Defined as blood pressure >140/90 mmHg at two following visits according to the European Society of Hypertension criteria. Diabetes Mellitus. Defined as fasting plasma glucose > 126 mg/dL at two following visits according to the World Health Organization. Dyslipidemia. Defined as hypercholesterolemia > 220mg/dL and hypertriglyceridemia >200mg/dL at two following visits. |
6th and 12th months post-transplant | |
| Primary | To compare the liver fibrosis progression (F=2 under ISHAK score) in patients who receive everolimus vs mTOR free immunosuppression | 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. | One year | |
| Secondary | To identify viral and recipient molecular predictors of fibrosis and anti-HCV treatment responses in liver transplant recipients under steroid-free immunosuppression | Serum samples from the recipient will be taken 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, 1d, 3d, 7d, 14d, 28d, 2m, 3m, 6m, 9m and 12m. Blood samples will be taken from the peripheral circulation and centrifugated within 2 to 3 hours after extraction, aliquoted, and frozen at -80 ºC. The concentration of HCV-RNA will be determined by using a quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay (Cobas Ampliprep/Cobas TaqMan; Roche Molecular Diagnostics, Barcelona, Spain) that achieves a sensitivity of 15 UI/mL. - DNA will be extracted from the liver donor and the recipient to characterize DNA polymorphisms. RNA Viral population complexity and presence of resistant mutations will be also studied using ultra-deep pyrosequence using eithre GS-Junior or GS-FLX platforms |
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 |