Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cyclosporine in Hepatitis C Infection Viral Clearance Following Liver Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00821587
Recruitment Status : Completed
First Posted : January 13, 2009
Results First Posted : December 8, 2011
Last Update Posted : December 8, 2011
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University of Florida

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C
Interventions Drug: Cyclosporine
Drug: Tacrolimus
Enrollment 39
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.
Arm/Group Title Tacrolimus Cyclosporine
Hide 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
Reason Not Completed
Physician Decision             0             1
Arm/Group Title Tacrolimus Cyclosporine Total
Hide 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 Number of Baseline Participants 20 19 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
20
 100.0%
19
 100.0%
39
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 19 participants 39 participants
54.4  (5.4) 52.2  (6.4) 53.3  (5.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
Female
2
  10.0%
5
  26.3%
7
  17.9%
Male
18
  90.0%
14
  73.7%
32
  82.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 19 participants 39 participants
20 19 39
1.Primary Outcome
Title Hepatitis C Viral Level
Hide Description Undetectable or <100 COPIES/ML
Time Frame 6 months after completion of interferon based therapy
Hide Outcome Measure Data
Hide 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)
Hide 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
Overall Number of Participants Analyzed 20 18
Measure Type: Number
Unit of Measure: Participants
7 7
Show Statistical Analysis 1 Hide 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
Comments [Not Specified]
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 [Not Specified]
Time Frame 72 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tacrolimus Cyclosporine
Hide 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 (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Tacrolimus Cyclosporine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      1/19 (5.26%)    
Immune system disorders     
Death  [1]  0/20 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
[1]
Liver biopsy was performed and showed severe chronic rejection
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tacrolimus Cyclosporine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/20 (80.00%)      17/19 (89.47%)    
Blood and lymphatic system disorders     
Neutropenia  [1]  8/20 (40.00%)  8 3/19 (15.79%)  4
Anemia  [1]  16/20 (80.00%)  20 16/19 (84.21%)  19
Thrombocytopenia  [1]  11/20 (55.00%)  11 10/19 (52.63%)  10
Gastrointestinal disorders     
Nausea * [2]  5/20 (25.00%)  8 5/19 (26.32%)  10
General disorders     
Fever * [2]  4/20 (20.00%)  16 4/19 (21.05%)  20
Insomnia * [2]  6/20 (30.00%)  6 9/19 (47.37%)  9
Psychiatric disorders     
Depression * [3]  8/20 (40.00%)  8 9/19 (47.37%)  9
Irritability * [2]  2/20 (10.00%)  6 3/19 (15.79%)  5
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
Labs
[2]
Reported by patient
[3]
Clinical Assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Roberto J. Firpi-Morell, MD
Organization: University of Florida
Phone: 352-273-9500 ext 9466
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00821587     History of Changes
Other Study ID Numbers: 20040658
First Submitted: January 9, 2009
First Posted: January 13, 2009
Results First Submitted: August 4, 2011
Results First Posted: December 8, 2011
Last Update Posted: December 8, 2011