Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant (A-WISH)
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Full description
This is a prospective multicenter, open-label, randomized trial in which individuals with liver failure due to hepatitis C or to nonimmune nonviral causes undergo liver transplantation and receive immunosuppression with a calcineurin inhibitor and corticosteroids. Corticosteroids are tapered in the 3 months after transplantation and the calcineurin inhibitor is continued. Participants are regularly assessed for evidence of allograft rejection. One year after transplantation, participants eligible for withdrawal are randomly assigned in a 4 to 1 ratio to immunosuppression withdrawal or to maintenance. Participants assigned to withdrawal undergo a scheduled taper over approximately 1 year.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- Male or female 18 years of age or older.
- Necessity for liver transplant.
- 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.
- Ability to provide informed consent.
- Availability of donor specimen(s).
- For individuals with hepatitis C infection, presence of hepatitis genomes in blood.
Exclusion criteria
- Previous transplant.
- Multiorgan or split liver transplant other than with a right trisegment.
- Living donor transplant.
- Donor liver from a donor positive for antibody against hepatitis C.
- Donor liver from a non-heart-beating donor.
- Liver failure due to autoimmune disease.
- Fulminant liver failure.
- Hepatitis B infection as defined by the presence of HbSAg or hepatitis-C infection with a genome other than genome 1.
- Stage III or higher hepatocellular cancer.
- 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%.
- Active systemic infection at the time of transplantation.
- Clinically significant chronic renal disease.
- Clinically significant cardiovascular or cerebrovascular disease.
- Infection with human immunodeficiency virus.
- Any investigational drug received within 6 weeks of study entry or any investigational vaccine received at any time.
- Hypersensitivity to tacrolimus.
- Unwillingness or inability to comply with study requirements.
Trial design
Primary purpose
Allocation
Interventional model
Masking
275 participants in 2 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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