Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal, Hepatitis |
| Therapuetic Areas: | Gastroenterology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/6/2019 |
| Start Date: | October 2005 |
| End Date: | September 2015 |
A Phase II Trial to Assess the Safety of Immunosuppression Withdrawal in Liver Transplant Recipients
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.
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.
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.
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.
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. Donor liver from a donor positive for antibody against hepatitis C.
5. Donor liver from a non-heart-beating donor.
6. Liver failure due to autoimmune disease.
7. Fulminant liver failure.
8. Hepatitis B infection as defined by the presence of HbSAg or hepatitis-C infection
with a genome other than genome 1.
9. Stage III or higher hepatocellular cancer.
10. 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%.
11. Active systemic infection at the time of transplantation.
12. Clinically significant chronic renal disease.
13. Clinically significant cardiovascular or cerebrovascular disease.
14. Infection with human immunodeficiency virus.
15. Any investigational drug received within 6 weeks of study entry or any investigational
vaccine received at any time.
16. Hypersensitivity to tacrolimus.
17. Unwillingness or inability to comply with study requirements.
We found this trial at
8
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