Trial Outcomes & Findings for Cyclosporine in Hepatitis C Infection Viral Clearance Following Liver Transplantation (NCT NCT00821587)

Last Updated: 2023-06-01

Results Overview

Number of Participants with Undetectable or Less than 100 copies/ml Hepatitis C Viral Level --defined as SVR -Sustained Virologic Response

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

39 participants

Primary outcome timeframe

6 months after completion of interferon based therapy

Results posted on

2023-06-01

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	20	19
Overall Study COMPLETED	20	18
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Physician Decision	0	1

Baseline Characteristics

Cyclosporine in Hepatitis C Infection Viral Clearance Following Liver Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tacrolimus n=20 Participants 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.	Cyclosporine n=19 Participants 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 n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	54.4 years STANDARD_DEVIATION 5.4 • n=5 Participants	52.2 years STANDARD_DEVIATION 6.4 • n=7 Participants	53.3 years STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	19 participants n=7 Participants	39 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Number of Participants with Undetectable or Less than 100 copies/ml Hepatitis C Viral Level --defined as SVR -Sustained Virologic Response

Outcome measures

Outcome measures
Measure	Tacrolimus (TAC) n=20 Participants Tacrolimus 0.08-0.12 mg/kg/day orally in two divided doses	Cyclosporine (CsA) n=18 Participants Cyclosporine 2.0-4.0 mg/kg/day orally in two divided doses
Number of Participants With Less Than 100 Hepatitis C Virus RNA Copies/mL	7 Participants	7 Participants

Adverse Events

Tacrolimus

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Cyclosporine

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tacrolimus n=20 participants at risk 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.	Cyclosporine n=19 participants at risk 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.
Immune system disorders Death	0.00% 0/20 • 72 weeks	5.3% 1/19 • Number of events 1 • 72 weeks

Other adverse events

Other adverse events
Measure	Tacrolimus n=20 participants at risk 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.	Cyclosporine n=19 participants at risk 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.
Blood and lymphatic system disorders Neutropenia	40.0% 8/20 • Number of events 8 • 72 weeks	15.8% 3/19 • Number of events 4 • 72 weeks
Blood and lymphatic system disorders Anemia	80.0% 16/20 • Number of events 20 • 72 weeks	84.2% 16/19 • Number of events 19 • 72 weeks
Blood and lymphatic system disorders Thrombocytopenia	55.0% 11/20 • Number of events 11 • 72 weeks	52.6% 10/19 • Number of events 10 • 72 weeks
Psychiatric disorders Depression	40.0% 8/20 • Number of events 8 • 72 weeks	47.4% 9/19 • Number of events 9 • 72 weeks
Gastrointestinal disorders Nausea	25.0% 5/20 • Number of events 8 • 72 weeks	26.3% 5/19 • Number of events 10 • 72 weeks
General disorders Fever	20.0% 4/20 • Number of events 16 • 72 weeks	21.1% 4/19 • Number of events 20 • 72 weeks
General disorders Insomnia	30.0% 6/20 • Number of events 6 • 72 weeks	47.4% 9/19 • Number of events 9 • 72 weeks
Psychiatric disorders Irritability	10.0% 2/20 • Number of events 6 • 72 weeks	15.8% 3/19 • Number of events 5 • 72 weeks

Additional Information

Roberto J. Firpi-Morell, MD

University of Florida

Phone: 352-273-9500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place