Phase 2
N=275
Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant
Hepatitis C · Hepatitis C, Chronic · Nonimmune Nonviral Causes of Liver Failure
Bottom Line
View on ClinicalTrials.gov: NCT00135694 ↗Enrolled (actual)
275
Serious AEs
55.3%
Results posted
Dec 2016
Primary outcome: Primary: Number of Participants With Clinical Complications Usually Attributed to Immunosuppression — 12; 4 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- calcineurin inhibitor-based immunosuppression (Drug); liver transplant (Procedure); corticosteroids (Drug); immunosuppression withdrawal (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Sep 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Clinical Complications Usually Attributed to Immunosuppression |
12; 4 | — |
| SECONDARY Number of Participants Who Qualify for Random Assignment |
95 | — |
| SECONDARY Number of Participants Who Successfully Stop Taking Immunosuppression for at Least 6 Months |
12 | — |
| SECONDARY Immunosuppression-free Duration |
555.2 | — |
| SECONDARY Number of Hepatitis C Infected Participants With Progression of Hepatitis C Related Liver Disease, Defined as Stage 4 or Higher Fibrosis on the Ishak Scale |
0; 0 | — |
| SECONDARY Number of Participants Experiencing Graft Loss or Death |
1; 0 | — |
| SECONDARY Total Immunosuppression From Month 21 to Month 24 Post-randomization |
2.8; 3.7 | 0.0183 sig |
| SECONDARY Total Burden of Immunosuppression From Random Assignment to Month 24 |
2198.5; 2708.4 | <0.0001 sig |
Summary
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.
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT00135694). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.