Cyclosporine in Hepatitis C Infection Viral Clearance Following Liver Transplantation
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Tacrolimus Tacrolimus |
Drug: Tacrolimus
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.
Other Names:
|
Active Comparator: Cyclosporine Cyclosporine |
Drug: Cyclosporine
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Florida
- Novartis Pharmaceuticals
Investigators
- Principal Investigator: Roberto J Firpi-Morell, MD, University of Florida
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20040658
Study Results
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 Detail | 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. |
Arm/Group Title | Tacrolimus | Cyclosporine |
---|---|---|
Arm/Group Description | 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. | 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. |
Period Title: Overall Study | ||
STARTED | 20 | 19 |
COMPLETED | 20 | 18 |
NOT COMPLETED | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Tacrolimus | Cyclosporine | Total |
---|---|---|---|
Arm/Group Description | 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. | 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. | Total of all reporting groups |
Overall Participants | 20 | 19 | 39 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
20
100%
|
19
100%
|
39
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
54.4
(5.4)
|
52.2
(6.4)
|
53.3
(5.9)
|
Sex: Female, Male (Count of Participants) | |||
Female |
2
10%
|
5
26.3%
|
7
17.9%
|
Male |
18
90%
|
14
73.7%
|
32
82.1%
|
Region of Enrollment (participants) [Number] | |||
United States |
20
100%
|
19
100%
|
39
100%
|
Outcome Measures
Title | Number of Participants With Less Than 100 Hepatitis C Virus RNA Copies/mL |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Tacrolimus (TAC) | Cyclosporine (CsA) |
---|---|---|
Arm/Group Description | Tacrolimus 0.08-0.12 mg/kg/day orally in two divided doses | Cyclosporine 2.0-4.0 mg/kg/day orally in two divided doses |
Measure Participants | 20 | 18 |
Count of Participants [Participants] |
7
35%
|
7
36.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Tacrolimus (TAC), Cyclosporine (CsA) |
---|---|---|
Comments | 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. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | We hypothesize that subjects on CsA are more likely to achieve undetectable viral level in patients receiving antiviral therapy for recurrent HCV after Liver Transplant | |
Method | Chi-squared | |
Comments |
Adverse Events
Time Frame | 72 weeks | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Tacrolimus | Cyclosporine | ||
Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
Tacrolimus | Cyclosporine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Tacrolimus | Cyclosporine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 1/19 (5.3%) | ||
Immune system disorders | ||||
Death | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Tacrolimus | Cyclosporine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 16/20 (80%) | 17/19 (89.5%) | ||
Blood and lymphatic system disorders | ||||
Neutropenia | 8/20 (40%) | 8 | 3/19 (15.8%) | 4 |
Anemia | 16/20 (80%) | 20 | 16/19 (84.2%) | 19 |
Thrombocytopenia | 11/20 (55%) | 11 | 10/19 (52.6%) | 10 |
Gastrointestinal disorders | ||||
Nausea | 5/20 (25%) | 8 | 5/19 (26.3%) | 10 |
General disorders | ||||
Fever | 4/20 (20%) | 16 | 4/19 (21.1%) | 20 |
Insomnia | 6/20 (30%) | 6 | 9/19 (47.4%) | 9 |
Psychiatric disorders | ||||
Depression | 8/20 (40%) | 8 | 9/19 (47.4%) | 9 |
Irritability | 2/20 (10%) | 6 | 3/19 (15.8%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Roberto J. Firpi-Morell, MD |
---|---|
Organization | University of Florida |
Phone | 352-273-9500 ext 9466 |
firpirj@medicine.ufl.edu |
- 20040658