Kidney Transplant RecipientsPhase 2NCT01517984
Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation
A Phase 2 study testing Tacrolimus (CNI) Withdrawal and Standard Immunosuppressive Therapy in people with Kidney Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 11 sites in 2 countries.
Trial 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transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn.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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant Recipients
- What is being tested?
- Tacrolimus (CNI) Withdrawal and Standard Immunosuppressive Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Nov 2010to May 2015
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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).
Who cannot join
- 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;
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- 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;
- Any condition that would preclude protocol biopsies;
- 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 of a subject to give written informed consent or comply with study protocol;
- Use of investigational drugs within 4 weeks of study entry and for the duration of the study;
- Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or equivalent.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States9 sites
University of Michigan Hospital
Ann Arbor, Michigan, 48109
Brigham & Women's Hospital
Boston, Massachusetts, 02115
University Hospitals of Cleveland
Cleveland, Ohio, 44106-5048
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
The Methodist Hospital
Houston, Texas, 77030
University of California Los Angeles
Los Angeles, California, 90055
Yale University School of Medicine
New Haven, Connecticut, 06520-8029
Mount Sinai School of Medicine
New York, New York, 10029
Washington University
St Louis, Missouri, 63110
Canada2 sites
Toronto General Hospital
Toronto, Ontario, M5G 2M1
Health Sciences Centre
Winnipeg, Manitoba, R3A IR9
About this study
Official title: Immune Monitoring and Calcineurin Inhibitor (CNI) Withdrawal in Low Risk Recipients of Kidney Transplantation
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.
Read the 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.
- Conditions
- Kidney Transplant Recipients
- Being tested
- Tacrolimus (CNI) Withdrawal, Standard Immunosuppressive Therapy
- Keywords
- recipients of living-donor kidney allografts, antithymocyte globulin (ATG) induction, calcineurin inhibitors (CNIs), CNI withdrawal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus (CNI) WithdrawalDrug
Also called ATG Induction,Tacrolimus (CNI), MMF and Prednisone, Followed by CNI Withdrawal, rabbit antithymocyte globulin (RATG), Thymoglobulin®, calcineurin inhibitor (CNI)
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.
Standard Immunosuppressive TherapyDrug
Also called ATG induction,Tacrolimus (CNI), MMF and Prednisone, rabbit antithymocyte globulin (RATG), Thymoglobulin®, calcineurin inhibitor (CNI)
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.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus (CNI) Withdrawal | Experimental | 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. Receives: Drug: Tacrolimus (CNI) Withdrawal; Drug: Standard Immunosuppressive Therapy |
| Standard Immunosuppressive Therapy | Active comparator | 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. Receives: Drug: Standard Immunosuppressive Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
Measured: 6 months post-transplantation, 24 months post-transplantation
Incidence of Acute Rejection
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.
Measured: 6 to 18 months post-randomization
Allograft Survival Rate
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.
Measured: 6 to 18 months post-randomization
Participant Survival Rate
Number of participants who did not die within the course of this study.
Measured: 6 to 18 months post-transplantation
Percentage of Participants With New Donor Specific Antibodies (DSAs)
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.
Measured: 6 to 18 months post-randomization
Percentage of Participants With Donor-Specific Memory Using Elispot
This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Measured: 6 to 18 months post-randomization
Percentage of Participants in the Experimental Arm Off Tacrolimus
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.
Measured: 18 months post-randomization
Incremental Change in IF/TA Scores
This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Measured: 6 to 18 months post-transplant
Measurement of Urinary Parameters Before and After Randomization
This endpoint was unable to be analyzed because the study was terminated early after stopping rules were met.
Measured: 6 months post-transplantation to 18 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startNov 2010
- Primary completionMay 2015
- Study completionMay 2015
Why it stopped: Absence of equipoise on the basis of predetermined stopping rules.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney Transplant RecipientsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Clinical Trials in Organ Transplantation
- Responsible party
- Sponsor
- Investigators
- Donald Hricik, MD, Study chair, University Hospitals Cleveland Medical CenterPeter S. Heeger, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517984
- Sponsor's protocol ID
- DAIT CTOT-09
- Status last verified
- Sep 2026
- First submitted
- 20 Jan 2012
- Last updated
- 24 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 25925687