Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant (AWISH)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00135694
First received: August 25, 2005
Last updated: March 26, 2014
Last verified: March 2014

August 25, 2005
March 26, 2014
October 2005
November 2014   (final data collection date for primary outcome measure)
Proportion of participants with progression of hepatitis C-related liver disease, [ Time Frame: Randomization to Year 2 ] [ Designated as safety issue: Yes ]

This is a composite endpoint comprising specific clinical complications related to immunosuppression and is defined as the occurrence anytime in the 24 months after random assignment of any one of the following:

  • death or graft loss,
  • grade 4 secondary malignancy, (graded by CTCAE 3.0),
  • grade 4 opportunistic infection, (graded by CTCAE 3.0),
  • gradestage 3 or higher fibrosis, or
  • grade 2 or higher decrease in renal function defined as follows:

    1. the eGFR using creatinine obtained prior to and closest to randomization will be considered the baseline and will be compared to the eGFR using creatinine obtained at 24 months +/- 3 months, in the absence of intercurrent illness, after randomization;
    2. for those with a baseline GFR 30-90 ml per min per 1.73 metersquared, a 25% decrease in GFR;
    3. for those with a baseline GFR greater than 90 ml per min per 1.73 meter-squared, a 25% decrease in GFR and a decrease
Proportion of participants with progression of hepatitis C-related liver disease, defined as Stage 4 or higher fibrosis on the Ishak scale, in the 2 years following random assignment
Complete list of historical versions of study NCT00135694 on ClinicalTrials.gov Archive Site
  • The proportion of participants who qualify for random assignment [ Time Frame: 1 to 2 years post-transplantation ] [ Designated as safety issue: No ]
  • The proportion of subjects who are successfully stop taking immunosuppression for at least 6 months [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Immunosuppression-free duration [ Time Frame: discontinuation of immunosuppression to end of trial participation or to time of restarting immunosuppression ] [ Designated as safety issue: No ]
  • Laboratory tests, mechanistic assays, or clinical assessments indicative of successful withdrawal [ Time Frame: immediately before and after immunosuppression withdrawal ] [ Designated as safety issue: No ]
  • Hepatitis C viral load [ Time Frame: immediately before and after immunosuppression withdrawal ] [ Designated as safety issue: Yes ]
  • In-vitro T-cell anti-hepatitis-C responses [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Histopathologic assessment for hepatitis in the allograft [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Definition of rejection profiles from laboratory tests, mechanistic studies, or clinical assessments [ Time Frame: after immunosuppression withdrawal ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • The proportion of graft loss or death [ Time Frame: randomization to 2 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Total burden of immunosuppression from random assignment [ Time Frame: randomization to 2 years ] [ Designated as safety issue: No ]
  • Long-term Renal Function [ Time Frame: randomization to 2 years ] [ Designated as safety issue: No ]
  • Tolerance induction
  • Laboratory tests indicative of successful withdrawal
  • Hepatitis C immune response and graft injury
  • Definition of rejection profiles from laboratory tests
Not Provided
Not Provided
 
Gradual Withdrawal of Immune System Suppressing Drugs in Patients Receiving a Liver Transplant
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C
  • Hepatitis C, Chronic
  • Nonimmune Nonviral Causes of Liver Failure
  • Drug: calcineurin inhibitor-based immunosuppression
    May be cyclosporine, mycophenolate mofetil, or tacrolimus
  • Procedure: liver transplant
    Occurs at study entry
  • Drug: corticosteroids
    3-month course of corticosteroids.
  • Other: 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.
  • Experimental: Immunosuppression Withdrawal
    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.
    Interventions:
    • Drug: calcineurin inhibitor-based immunosuppression
    • Procedure: liver transplant
    • Drug: corticosteroids
    • Other: immunosuppression withdrawal
  • Active Comparator: Immunosuppression Maintenance
    Liver transplant, followed by maintenance doses of continuous calcineurin inhibitor-based immunosuppression therapy.
    Interventions:
    • Drug: calcineurin inhibitor-based immunosuppression
    • Procedure: liver transplant
    • Drug: corticosteroids
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
275
November 2015
November 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00135694
DAIT ITN030ST
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Study Chair: Abraham Shaked, MD, PhD University of Pennsylvania
National Institute of Allergy and Infectious Diseases (NIAID)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP