Hepatitis C
Conditions
Keywords
Hepatitis C Post Liver Transplant
Brief summary
The purpose of this study is to evaluate the effect of cyclosporine, an anti-rejection drug, on the clearance of the hepatitis C virus in liver transplant subjects being treated with peg-interferon and ribavirin.
Detailed description
This is a randomized, single-center controlled study comparing two different immunosuppression regimens (CsA and TAC) in patients with recurrent HCV after LT undergoing antiviral therapy for HCV.
Interventions
DRUGCyclosporine
Patients randomized to CsA had TAC discontinued and were treated with CsA at a dose of 2.0-4.0 mg/kg/day orally in two divided doses with target trough whole blood concentrations of 150-200 ng/ml.
DRUGTacrolimus
Patients receiving TAC were treated with a dose of 0.08-0.12 mg/kg/day orally in two divided doses with target trough whole blood concentrations of 10-15 ng/ml for the first month post-transplant followed by 5-10 ng/ml thereafter. Immunosuppression was typically tapered to monotherapy (TAC alone) within 4-6 months of transplantation.
Sponsors
Novartis Pharmaceuticals
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females age 18 years and older * HCV RNA positive by PCR after liver transplantation * Elevated ALT at any time point after liver transplantation * Protocol liver biopsy (standard of care) consistent with Stage greater than or equal to 2 of Ishak fibrosis score after liver transplantation * Able to provide written informed consent * Willing to practice acceptable birth control during the study period.
Exclusion criteria
* Decompensated Cirrhosis * hemoglobin \< 12 g/dl * WBC \< 3,500/cubic mm * Platelets \< 75,000/cubic mm * Human immunodeficiency virus infection * Pregnancy * Positive HbsAg * History of coronary artery disease, history of seizure disorder, poorly controlled autoimmune conditions, thyroid dysfunction, diabetes mellitus, major psychosis, intolerance to previous interferon-based therapy other than anemia or neutropenia * History of suicidal ideation or suicidal attempts * Creatinine \> 2.0 mg/dl * Severe non-hepatic illnesses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Less Than 100 Hepatitis C Virus RNA Copies/mL | 6 months after completion of interferon based therapy | Number of Participants with Undetectable or Less than 100 copies/ml Hepatitis C Viral Level --defined as SVR -Sustained Virologic Response |
Participant flow
Recruitment details
The study was conducted at the University of Florida in Gainesville between July 2004 and April 2008. Patients attended clinic visits at the time of randomization (baseline) and at 12-week intervals for 72 weeks.
Pre-assignment details
Subjects with Hepatitis C Virus (HCV) recurrence Ishak Stage2 were enrolled and randomized to stay on Tacrolimus (TAC) or to change to Cyclosporine (CsA) for baseline immunosuppression with 1-month washout period before initiation of therapy with Pegylated Interferon Alfa2a and ribavirin for 48 weeks for genotype-1, or 24 weeks for genotype-3.
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus Patients receiving TAC are treated with a dose of 0.08- 0.12 mg/kg/day orally in two divided doses with target trough whole blood concentrations of 10-15 ng/ml for the first month post-transplant followed by 5-10 ng/ml thereafter. | 20 |
| Cyclosporine Patients randomized to CsA will have TAC discontinued and will be treated with CsA at a dose of 2.0-4.0 mg/kg/day orally in two divided doses with target trough whole blood concentrations of 150-200 ng/ml. | 19 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Cyclosporine | Tacrolimus | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 20 Participants | 39 Participants |
| Age, Continuous | 52.2 years STANDARD_DEVIATION 6.4 | 54.4 years STANDARD_DEVIATION 5.4 | 53.3 years STANDARD_DEVIATION 5.9 |
| Region of Enrollment United States | 19 participants | 20 participants | 39 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 14 Participants | 18 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 20 | 17 / 19 |
| serious Total, serious adverse events | 0 / 20 | 1 / 19 |
Outcome results
Primary
Number of Participants With Less Than 100 Hepatitis C Virus RNA Copies/mL
Number of Participants with Undetectable or Less than 100 copies/ml Hepatitis C Viral Level --defined as SVR -Sustained Virologic Response
Time frame: 6 months after completion of interferon based therapy
Population: Randomization was performed using computer-generated random numbers. 150 patients were eligible and 39 met entry criteria for enrollment in the study. Subjects with HCV recurrence (Ishak Stage2) were randomized to TAC or to change to CsA before initiation of therapy with PEGa-2a and ribavirin for 48 weeks for genotype-1,or 24 weeks for genotype-3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tacrolimus (TAC) | Number of Participants With Less Than 100 Hepatitis C Virus RNA Copies/mL | 7 Participants |
| Cyclosporine (CsA) | Number of Participants With Less Than 100 Hepatitis C Virus RNA Copies/mL | 7 Participants |
Comparison: We hypothesize that subjects on CsA are more likely to achieve undetectable viral levels after liver transplant. Comparisons between the two groups (Undetectable viral level vs. Detectable viral level) were performed with Pearson Chi-square tests or Fisher's exact test for categorical variables, and Mann-Whitney U test for continuous variables.p-value: <0.05Chi-squared