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

Mayo Clinic

Status and phase: Enrolling; Phase 4

Conditions: Mycophenolate Mofetil; Kidney Transplantation

Treatments: Drug: Mycophenolate Mofetil (MMF) Maintenance Group; Drug: Mycophenolate Mofetil (MMF) Withdrawal Group

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06568549

24-002574

Details and patient eligibility

About

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.

Full 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 kidney biopsy, 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on current medication, or the subject will be placed into the MMF Withdrawal group which means they would slowly be withdrawn from this medication.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.

Enrollment: 350 estimated patients

Sex: All

Ages: 55+ years old

Volunteers: Accepts Healthy Volunteers

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).

• 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. compromises their well-being) or that could prevent, or limit the protocol specified assessment.

  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 standard of care biopsy Subjects experiencing rejection will not be eligible for randomization and MMF withdrawal.

• Subjects who are unable to undergo their 4-month standard of care kidney biopsy due to medical contraindications.

• De novo DSA

• Subjects who are not maintained on tacrolimus, mycophenolate mofetil of Myfortic. Subjects who are not on tacrolimus and mycophenolate mofetil or Myfortic at the time of randomization will be placed in the non-randomized group.

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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350 participants in 3 patient groups

Non-Randomized Group

No Intervention group

Description:

Individuals who do not meet eligibility for randomization will continue in the study and continue to follow study related visits. Individuals will continue with their current immunosuppression medication.

MMF Maintenance Group

Active Comparator group

Description:

Individuals randomized to the MMF Maintenance Group will not be withdrawn from their MMF and will continue to follow their standard of care immunosuppression medications.

Treatment:

Drug: Mycophenolate Mofetil (MMF) Maintenance Group

MMF Withdrawal Group

Experimental group

Description:

Individuals randomized to the MMF Maintenance Group will be withdrawn from their MMF immunosuppression medication from Month 4 to Month 10 post-transplant.

Treatment:

Drug: Mycophenolate Mofetil (MMF) Withdrawal Group