Study Stopped
Absence of equipoise on the basis of predetermined stopping rules.
Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation
Immune Monitoring and Calcineurin Inhibitor (CNI) Withdrawal in Low Risk Recipients of Kidney Transplantation
1 other identifier
interventional
52
2 countries
11
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transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn.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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2010
Typical duration for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2010
CompletedFirst Submitted
Initial submission to the registry
January 20, 2012
CompletedFirst Posted
Study publicly available on registry
January 25, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2015
CompletedResults Posted
Study results publicly available
November 30, 2016
CompletedSeptember 11, 2017
August 1, 2017
4.5 years
January 20, 2012
June 16, 2016
August 10, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Incremental IF/A Scores >2 at 24 Months Post-Randomization
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.
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.
Secondary Outcomes (9)
Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation
6 months post-transplantation, 24 months post-transplantation
Incidence of Acute Rejection
6 to 18 months post-randomization
Allograft Survival Rate
6 to 18 months post-randomization
Participant Survival Rate
6 to 18 months post-transplantation
Percentage of Participants With New Donor Specific Antibodies (DSAs)
6 to 18 months post-randomization
- +4 more secondary outcomes
Study Arms (2)
Tacrolimus (CNI) Withdrawal
EXPERIMENTALSubjects 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
ACTIVE COMPARATORSubjects 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.
Interventions
Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a 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 will be 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 regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.
Eligibility Criteria
You may qualify if:
- Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible for enrollment as study subjects:
- Subject must be able to understand and provide written informed consent;
- Primary living-donor (related or unrelated) kidney transplant recipients;
- Peak flow-based PRAs for class I and class II \<30%(performed by local center);
- Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and class II \<30% (performed by local center);
- No donor specific antibody by flow solid phase method on the peak PRA serum (if serum available), or on the current PRA serum (within 8 weeks prior to transplantation) performed by central core laboratory. If the sera for the peak PRA is not available, then only the current PRA serum will be tested;
- Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);
- Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) upon study entry;
- Female and male subjects with reproductive potential must agree to use FDA approved methods of birth control while participating in the study.
- Participants who meet all of the following criteria are eligible for randomization:
- No history of acute rejection episodes;
- The pre-randomization protocol biopsy should confirm no rejection, including borderline rejection (based on the central pathology read);
- No donor specific antibody as detected by flow solid phase method (performed by the central core laboratory).
You may not qualify if:
- Initial Enrollment/Screening:
- Participants who meet any of these criteria are not eligible for enrollment as study subjects:
- Recipient of multiple organ transplants;
- Prior history of organ transplantation;
- Deceased-donor source;
- Any condition that would preclude protocol biopsies;
- HLA identical recipients;
- Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;
- Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
- Inability or unwillingness to comply with study protocol;
- Use of investigational drugs within 4 weeks of study entry and for the duration of the study;
- Recent recipient of any licensed or investigational live attenuated vaccine(s) within two months of prior to study entry.
- Participants who meet any of these criteria are not eligible for randomization:
- Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction therapy;
- Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
University of California Los Angeles
Los Angeles, California, 90055, United States
Yale University School of Medicine
New Haven, Connecticut, 06520-8029, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109, United States
Washington University
St Louis, Missouri, 63110, United States
Mount Sinai School of Medicine
New York, New York, 10029, United States
University Hospitals of Cleveland
Cleveland, Ohio, 44106-5048, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
The Methodist Hospital
Houston, Texas, 77030, United States
Health Sciences Centre
Winnipeg, Manitoba, R3A IR9, Canada
Toronto General Hospital
Toronto, Ontario, M5G 2M1, Canada
Related Publications (1)
Hricik DE, Formica RN, Nickerson P, Rush D, Fairchild RL, Poggio ED, Gibson IW, Wiebe C, Tinckam K, Bunnapradist S, Samaniego-Picota M, Brennan DC, Schroppel B, Gaber O, Armstrong B, Ikle D, Diop H, Bridges ND, Heeger PS; Clinical Trials in Organ Transplantation-09 Consortium. Adverse Outcomes of Tacrolimus Withdrawal in Immune-Quiescent Kidney Transplant Recipients. J Am Soc Nephrol. 2015 Dec;26(12):3114-22. doi: 10.1681/ASN.2014121234. Epub 2015 Apr 29.
PMID: 25925687RESULT
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
After meeting protocol stopping rules, this trial was closed to new enrollment and randomization. No additional prespecified withdrawal of tacrolimus was allowed. Those already enrolled or randomized were followed for up to 24 months post-transplant.
Results Point of Contact
- Title
- Director, Clinical Research Operations Program
- Organization
- DAIT/NIAID
Study Officials
- STUDY CHAIR
Donald Hricik, MD
University Hospitals Cleveland Medical Center
- PRINCIPAL INVESTIGATOR
Peter S. Heeger, MD
Icahn School of Medicine at Mount Sinai
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 20, 2012
First Posted
January 25, 2012
Study Start
November 1, 2010
Primary Completion
May 1, 2015
Study Completion
May 1, 2015
Last Updated
September 11, 2017
Results First Posted
November 30, 2016
Record last verified: 2017-08