Reduced Immunosuppression in Older Renal Transplant Recipients With Trugraf®/TRAC Monitoring (RIOT Trial): A Prospective, Randomized, Multicenter Trial.

Official title

Reduced Immunosuppression in Older Renal Transplant Recipients With Trugraf® Monitoring (RIOT Trial): A Prospective, Randomized, Multicenter Trial.

Overview

The purpose of this research is to determine the safety and efficacy of withdrawing MMF (Mycophenolate Mofetil) in kidney transplant recipients who are 55 years or older at the time of receiving a kidney transplant. We are comparing them to patients who receive the standard of care Mycophenolate Mofetil.

Detailed description

Participation will be two years and it involves blood collection, collection of medical information and images from standard of care kidney biopsies. Subjects will be asked to complete questionnaires for the study at 12 and 24 months after kidney transplant. The research blood tests that are being collected for the study are called Trugraf®, Eurofins TRAC®, Trac-ID and Immunophenotyping and Single Cell RNA -sequencing. The principal investigator is using this test to see if they can predict and monitor rejection and viral infections in our kidney transplant patients. Immunophenotyping and single cell RNA sequencing tests are being done to identify unique gene expression profiles and their functions in different immune cells.

At the time of the 4 month standard of care follow up visit, if participants have not experienced any rejection episodes or formed any donor specific antibodies (dnDSA) and are still eligible, randomization will occur. Participants will be put into 1 of 2 groups: Mycophenolate Mofetil Maintenance group where the subject would continue on current medication, or the subject will be placed into the MMF Withdrawal group which means they would slowly be withdrawn from this medication. If the subject is not eligible to be randomized, they will remain in the study and placed into the Non-Randomized group and continue to have study related visits and procedures like the MMF Maintenance group.

Interventions

• Drug Mycophenolate Mofetil (MMF) Maintenance Group
  Mycophenolate Mofetil (MMF), administered orally as standard of care post kidney transplant as part of their immunosuppression regimen. Maintenance in Immunosuppression medication.
• Drug Mycophenolate Mofetil (MMF) Withdrawal Group
  Mycophenolate Mofetil (MMF), administered orally as standard of care post kidney transplant as part of their immunosuppression regimen. Withdrawal of MMF immunosuppression medication.

Primary outcome measures

• Acute Rejection [Time frame: 4 to 24 months post transplant.]
• Patient Deaths [Time frame: 4 to 24 months post transplant.]
• Graft Failure [Time frame: 4 to 24 months post transplant.]

Secondary outcome measures (7)

• Serious Adverse Events (SAE) [Time frame: 1 and 2 years post transplant.]
• eGFR (estimated glomerular filtration rate) [Time frame: 2 years post transplant]
• Single antigen beads (SAB) for donor-specific antibodies [Time frame: Baseline, 1 year post transplant and 2 years post transplant]
• BANFF scores [Time frame: 2 years post transplant.]
• Absolute lymphocyte counts [Time frame: 1 year post transplant and 2 years post transplant]
• Transplant Related Symptom (CIRS) Questionnaire [Time frame: 2 years post transplant.]
• Albumin/Creatinine Ratio (Microalbumin) Urine [Time frame: 2 years post transplant]

Eligibility criteria

Inclusion criteria

• Solitary kidney transplant recipient >55 years of age. At most 1 prior solitary kidney transplant.
• No other solid organ transplant though recipients of autologous stem cell transplants are eligible.
• HIV negative.
• Subjects must be on tacrolimus and mycophenolate mofetil or Myfortic at the time of consent. Prednisone at the time of consent is optional and is per local standard of care. Patients randomized to MMF withdrawal will be placed on prednisone 5mg/d at 4 months. Use of other immunosuppression medications for maintenance (cyclosporine, azathioprine, belatacept, sirolimus) is excluded.

Exclusion criteria

Time of Transplant Exclusion Criteria:

• The results of the most recent DSA testing indicate DSA with an MFI >2000.
• The results of the most recent cPRA testing indicate cPRA is above >80% (based on MFI >2000).

4-Month Exclusion Criteria:

• Acute rejection episode either clinical or on biopsy (greater than borderline). Subjects must not experience any type of rejection episodes from the time of transplant and must not show any signs of rejection (Cellular or Antibody mediated rejection, excluding borderline) at their 4-month biopsy (If obtained per standard of care). Subjects experiencing rejection will not be eligible for randomization and MMF withdrawal.
• De novo DSA
• Subjects who are not on tacrolimus at the time of randomization will be placed in the non-randomized group.
• Subjects who at the time of or prior to randomization were maintained on mycophenolate mofetil or Myfortic and have had their medication held or temporarily discontinued due to clinical indications (toxicity to the medication, polyoma virus infections, cancer, etc.) remain eligible for randomization.
• Has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings which, in the opinion of the investigator, would make study participation not in the participants best interest (e.g., compromise the well-being) or that could prevent, or limit the protocol-specified assessment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Mayo Clinic — Phoenix
• Mayo Clinic — Jacksonville
• Mayo Clinic — Rochester

Identifiers

NCT: NCT06568549 · 24-002574

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗