Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation
- Conditions
- Kidney Transplant Recipients
- Interventions
- Drug: Standard Immunosuppressive Therapy
- Registration Number
- NCT01517984
- Brief Summary
The study will compare how well transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn. In addition, this research study will evaluate whether reducing immunosuppression can decrease some of these side effects while still preventing rejection of the kidney.
- Detailed Description
Kidney transplantation is a treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients take immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. All anti-rejection medications have unwanted side effects. The purpose of this study is to evaluate the safety of slowly removing tacrolimus, a CNI.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 52
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tacrolimus (CNI) Withdrawal Tacrolimus (CNI) Withdrawal Subjects randomized (2:1) to tacrolimus (CNI) withdrawal. Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test are randomized (2:1) to tacrolimus (CNI) withdrawal. Tacrolimus (CNI) Withdrawal Standard Immunosuppressive Therapy Subjects randomized (2:1) to tacrolimus (CNI) withdrawal. Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test are randomized (2:1) to tacrolimus (CNI) withdrawal. Standard Immunosuppressive Therapy Standard Immunosuppressive Therapy Subjects randomized to standard immunosuppressive therapy, without subsequent tacrolimus (CNI) withdrawal. Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus. Tacrolimus (CNI) withdrawal does not occur.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Incremental IF/A Scores >2 at 24 Months Post-Randomization IF/TA scores on protocol biopsies obtained at 24 months post-randomization will be compared to those obtained at the time of implantation for this measurement. The investigators were not able to assess this outcome, the effect of the intervention on interstitial fibrosis/tubular atrophy (IF/TA; on a 2-year graft biopsy) due to the study's premature termination by the Data Safety Monitoring Board (DSMB) because of absence of equipoise on the basis of predetermined stopping rules.
- Secondary Outcome Measures
Name Time Method Measurement of Urinary Parameters Before and After Randomization 6 months post-transplantation to 18 months post-randomization This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation 6 months post-transplantation, 24 months post-transplantation Estimated glomerular filtration rate (eGFR) is a test to measure the level of kidney function. In this measure, the effects of tacrolimus withdrawal on long-term kidney function was assessed by comparing absolute 24 month eGFR (18 months post-randomization) and change in eGFR from 6 to 24 months (randomization to 18 months randomization). Lower numbers indicate poorer kidney function
Participant Survival Rate 6 to 18 months post-transplantation Number of participants who did not die within the course of this study.
Percentage of Participants With New Donor Specific Antibodies (DSAs) 6 to 18 months post-randomization Donor specific antibodies are antibodies that are directed against antigens expressed on donor organs. These antibodies can result in an immune attack on the transplanted organ, increasing risk of graft loss and/or rejection.
Incidence of Acute Rejection 6 to 18 months post-randomization Acute renal allograft rejection is defined as histological reading of borderline or greater determined by the local pathology laboratory. Participants suspected of having a rejection episode on the basis of clinical signs, symptoms, or on the basis of laboratory tests, had a renal ultrasound and underwent a renal transplant biopsy. Any detection of acute cellular rejection or acute humoral rejection resulted in participants in the 'Randomized to Tacrolimus Withdrawal' group to be restarted on tacrolimus and followed per the reduced follow-up schedule of events.
Allograft Survival Rate 6 to 18 months post-randomization Allograft survival is defined as participants who did not need to be re-transplanted or placed on dialysis due to the failure of their allograft transplantation during the course of this study.
Percentage of Participants in the Experimental Arm Off Tacrolimus 18 months post-randomization Participants in the 'Randomized to Tacrolimus Withdrawal' group were considered fully withdrawn once they no longer received any doses of tacrolimus. Participants met this endpoint if they did not resume taking tacrolimus as of 18 months post randomization with stable allograft function and without rejection of donor-specific antibodies.
Incremental Change in IF/TA Scores 6 to 18 months post-transplant This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Percentage of Participants With Donor-Specific Memory Using Elispot 6 to 18 months post-randomization This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Trial Locations
- Locations (11)
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Health Sciences Centre
🇨🇦Winnipeg, Manitoba, Canada
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
University of Michigan Hospital
🇺🇸Ann Arbor, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
The Methodist Hospital
🇺🇸Houston, Texas, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States