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

Phase 4
Not yet recruiting
Conditions
Kidney Transplantation
Mycophenolate Mofetil
Interventions
Registration Number
NCT06568549
Lead Sponsor
Mayo Clinic
Brief Summary

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® and Viracor® Trac. The principal investigator is using this test to see if they can predict and monitor rejection in our kidney transplant patients.

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on current medication, or the subject will be placed into the MMF Withdrawal group which means they would slowly be withdrawn from this medication.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

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
350
Inclusion Criteria
  • Solitary kidney transplant recipient >55 years of age-first or second transplants.
  • No other solid organ transplant though recipients of autologous stem cell transplants are eligible.
  • HIV negative.
Exclusion Criteria

Time of Transplant Exclusion Criteria:

  • DSA MFI >500

  • cPRA >80% (based on MFI .2000)

  • Prior treatment with MMF or need for MMF therapy (To treat a disease including their primary disease).

  • 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.

  • De novo DSA

  • 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MMF Withdrawal GroupMycophenolate Mofetil (MMF) Withdrawal GroupIndividuals randomized to the MMF Maintenance Group will be withdrawn from their MMF immunosuppression medication from Month 4 to Month 10 post-transplant.
MMF Maintenance GroupMycophenolate Mofetil (MMF) Maintenance GroupIndividuals randomized to the MMF Maintenance Group will not be withdrawn from their MMF and will continue to follow their standard of care immunosuppression medications.
Primary Outcome Measures
NameTimeMethod
Graft Failure4 to 24 months post transplant.

Total number of subjects to experience graft failure from the renal transplant

Patient Deaths4 to 24 months post transplant.

Total number of subject deaths from 4-24 months post transplant.

Acute Rejection4 to 24 months post transplant.

Total number of subjects to experience acute rejection of the renal transplant

Secondary Outcome Measures
NameTimeMethod
eGFR (estimated glomerular filtration rate)2 years post transplant

eGFR is calculated from a lab blood test using a formula that measures the level of creatinine. In this test a higher number is better. An eGFR value lower than 60 is a sign that the kidneys may not be working properly. Measured as mL/min/1

BANFF scores2 years post transplant.

The Banff 2018 classification involves scoring numerous characteristics of renal biopsy specimens. The scores can take values of 0, 1, 2, or 3 for each characteristic, indicating increasing severity of disease as the scores increase.

Transplant Related Symptom (CIRS) Questionnaire2 years post transplant.

The CIRS questionnaire is a 36-item questionnaire that contains statements that rate transplant symptoms on a scale of 1(None) to 5 (Very Severe). Total scores range from 36-180, lower scores indicate less severe symptoms, higher scores indicate more severe symptoms.

Serious Adverse Events (SAE)1 and 2 years post transplant.

The total number of subjects to experience SAE's. Defined as subjects experience any one of the following: acute cellular or antibody medicated rejection, borderline rejection or dnDSA (De novo donor-specific antibodies)

Single antigen beads (SAB) for donor-specific antibodiesBaseline, 1 year post transplant and 2 years post transplant

Single antigen bead (SAB) assay is a lab blood test used to detect human leukocyte antigen antibodies (HLA) and assessing the immunological risk for organ transplant. For HLA-DRβ1/3/4/5 the single molecule mismatches can range from 0-22 and for HLA-DQα1/β1 the single molecule mismatches range from 0-31. Measured as pg/mL.

Albumin/Creatinine Ratio (Microalbumin) Urine2 years post transplant

The urine albumin-creatinine ratio (uACR) test measures the amount of two different substances in urine - albumin (a protein) and creatinine. A value of 30 or higher suggests a higher risk for kidney failure. Measured as mg/g

Absolute lymphocyte counts1 year post transplant and 2 years post transplant

An absolute lymphocytes count is determined by multiplying the total number of white blood cells by the percentage of white blood cells that are lymphocytes. The normal range for lymphocytes is between 800 and 5000 (0.8-5.0) lymphocytes per mL of blood. A normal lymphocytes percentage is 18-45% of total white blood cells. Measured as cells per microliter (cells/µL)

Trial Locations

Locations (1)

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

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