This trial is active, not recruiting.

Conditions hepatitis c, hepatitis c, chronic, nonimmune nonviral causes of liver failure
Treatments calcineurin inhibitor-based immunosuppression, liver transplant, corticosteroids, immunosuppression withdrawal
Phase phase 2
Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator Immune Tolerance Network (ITN)
Start date October 2005
End date September 2015
Trial size 275 participants
Trial identifier NCT00135694, DAIT ITN030ST


In order to prevent organ rejection, patients receiving liver transplants currently require life-long treatment with immune system-suppressing medications to prevent the rejection of the transplanted liver. However, these medications can cause long-term side effects, such as infection, kidney problems, diabetes, and cancer. In patients infected with hepatitis C virus (HCV), these medications may increase the risk of HCV infection in the transplanted liver. The purpose of this study is to determine whether a slow withdrawal of immune system-suppressing medications is safe in two groups of subjects: those who receive a liver transplant due to HCV, and those who receive a liver transplant due to non-immune, non-viral causes of liver failure. The study will also look at whether slow withdrawal will help reduce the long-term side effects of immune system-suppressing medications and decrease the chance for HCV infection of the new liver in transplant patients with HCV.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Subjects may randomize to this group at 12 to 24 months after transplantation. This is followed by tapered withdrawal of calcineurin inhibitor-based immunosuppression therapy over the course of 1 year.
calcineurin inhibitor-based immunosuppression
May be cyclosporine, mycophenolate mofetil, or tacrolimus
liver transplant
Occurs at study entry
3-month course of corticosteroids.
immunosuppression withdrawal
One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance.
(Active Comparator)
Liver transplant, followed by maintenance doses of continuous calcineurin inhibitor-based immunosuppression therapy.
calcineurin inhibitor-based immunosuppression
May be cyclosporine, mycophenolate mofetil, or tacrolimus
liver transplant
Occurs at study entry
3-month course of corticosteroids.

Primary Outcomes

Proportion of participants with progression of hepatitis C-related liver disease,
time frame: Randomization to Year 2

Secondary Outcomes

The proportion of participants who qualify for random assignment
time frame: 1 to 2 years post-transplantation
The proportion of subjects who are successfully stop taking immunosuppression for at least 6 months
time frame: throughout study
Immunosuppression-free duration
time frame: discontinuation of immunosuppression to end of trial participation or to time of restarting immunosuppression
Laboratory tests, mechanistic assays, or clinical assessments indicative of successful withdrawal
time frame: immediately before and after immunosuppression withdrawal
Hepatitis C viral load
time frame: immediately before and after immunosuppression withdrawal
In-vitro T-cell anti-hepatitis-C responses
time frame: throughout study
Histopathologic assessment for hepatitis in the allograft
time frame: throughout study
Definition of rejection profiles from laboratory tests, mechanistic studies, or clinical assessments
time frame: after immunosuppression withdrawal
The proportion of hepatitis C-infected participants with progression of hepatitis-C-related liver disease, defined as stage 4 or higher fibrosis on the Ishak scale
time frame: randomization to 2 years
The proportion of graft loss or death
time frame: randomization to 2 years
Total immunosuppression, defined as the daily immunosuppression score in units per day averaged over the 3-month period
time frame: from month 21 after randomization to year 2
Total burden of immunosuppression from random assignment
time frame: randomization to 2 years
Long-term Renal Function
time frame: randomization to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Male or female 18 years of age or older. 2. Necessity for liver transplant. 3. For females of childbearing potential: a negative pregnancy test at study entry and agreement to use approved methods of birth control for the duration of their participation . 4. Ability to provide informed consent. 5. Availability of donor specimen(s). 6. For individuals with hepatitis C infection, presence of hepatitis genomes in blood. Exclusion Criteria: 1. Previous transplant. 2. Multiorgan or split liver transplant other than with a right trisegment. 3. Living donor transplant. 4. [deleted criterion 4] 5. Donor liver from a donor positive for antibody against hepatitis C. 6. Donor liver from a non-heart-beating donor. 7. Liver failure due to autoimmune disease. 8. Fulminant liver failure. 9. Hepatitis B infection as defined by the presence of HbSAg or hepatitis-C infection with a genome other than genome 1. 10. Stage III or higher hepatocellular cancer. 11. History of malignancy except hepatocellular cancer, adequately treated in situ cervical carcinoma, adequately treated basal or squamous cell carcinoma of skin, or other cancer judged to have a 5- year risk of recurrence less than 10%. 12. Active systemic infection at the time of transplantation. 13. Clinically significant chronic renal disease. 14. Clinically significant cardiovascular or cerebrovascular disease. 15. Infection with human immunodeficiency virus. 16. Any investigational drug received within 6 weeks of study entry or any investigational vaccine received at any time. 17. Hypersensitivity to tacrolimus. 18. Unwillingness or inability to comply with study requirements.

Additional Information

Official title A Phase II Trial to Assess the Safety of Immunosuppression Withdrawal in Liver Transplant Recipients
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by National Institute of Allergy and Infectious Diseases (NIAID).