Phase III Multicenter Open-label Randomized Clinical Trial Comparing Everolimus and Low Dose Tacrolimus to Tacrolimus and Mycophenolate Mofetil at 6 mo Post-Transplant to Prevent Long-term Complications After Pediatric Heart Transplantation

P00025970

The TEAMMATE Trial will enroll 210 pediatric heart transplant patients from 25 centers at 6 months post-transplant and follow each patient for 2.5 years. Half of the participants will receive everolimus and low-dose tacrolimus and the other half will receive tacrolimus and mycophenolate mofetil. The trial will determine which treatment is better at reducing the cumulative risk of coronary artery vasculopathy, chronic kidney disease and biopsy proven-acute cellular rejection without an increase in graft loss due to all causes (e.g. infection, PTLD, antibody mediated rejection).

2018-01-29

2023-04-17

2024-01-01

Active (not recruiting)

Early phase I

211

Inclusion Criteria: 1. Orthotopic heart transplantation 2. Age \< 21 years at time of transplant 3. Stable immunosuppression at the time of randomization with no contraindication to everolimus, tacrolimus, or mycophenolate mofetil 4. Planned follow-up at a study site for the 30 month duration of the study. 5. Subject or legal adult representative capable of providing informed consent (in general, assent will be sought for children aged 12 years or older). Exclusion Criteria: 1. Multi-organ transplant (e.g. heart-lung or heart-liver). 2. Known hypersensitivity to everolimus, sirolimus, tacrolimus or mycophenolate mofetil (MMF), or to components of the drug products. 3. Patients on maintenance corticosteroid therapy exceeding a dose equivalent of prednisone 0.1 mg/kg/day at randomization. 4. High-risk for rejection defined as active rejection, recurrent (≥ 2 episodes of grade 2R rejection) cellular rejection, recurrent rejection (≥ 2 episodes of any grade) with hemodynamic compromise, steroid-resistant rejection or unresolved antibody-mediated rejection during the first 6 months post-heart transplant 5. Graft dysfunction (LVEF \<40% or wedge pressure \>22 mmHg or cardiac index \<2.2 L/min/m2) 6. Stage 4 or 5 CKD (eGFR \<30 ml/min/1.73 m2) 7. Moderate or severe proteinuria 8. Active infection requiring hospitalization or treatment dose medical therapy. 9. Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the Site Principal Investigator. 10. Fasting Serum Cholesterol ≥300 mg/dL OR greater than or equal to 7.75 mmol/L, AND fasting triglycerides ≥2.5x the upper limit of normal (ULN). Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication, and reduction of serum cholesterol and triglyceride levels to below exclusion ranges is confirmed. 11. Uncontrolled diabetes mellitus. 12. Diagnosis of post-transplant lymphoproliferative disorder (PTLD) during the first 6 months post-heart transplant. 13. History of non-adherence to medical regimens. 14. Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and cannot discontinue the treatment 15. Patients who are pregnant or breast-feeding or intend to get pregnant during the study period.

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2023-10-17