Chronic Kidney Diseases Clinical Trial
— TEAMMATEOfficial title:
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
Verified date | October 2023 |
Source | Boston Children's Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Active, not recruiting |
Enrollment | 211 |
Est. completion date | January 2024 |
Est. primary completion date | April 17, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 21 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | University of Michigan Medical Center | Ann Arbor | Michigan |
United States | Children's Healthcare of Atlanta Emory | Atlanta | Georgia |
United States | Children's Hospital Colorado | Aurora | Colorado |
United States | Children's of Alabama | Birmingham | Alabama |
United States | Boston Children's Hospital | Boston | Massachusetts |
United States | Children's Hospital at Montefiore | Bronx | New York |
United States | Lurie Children's Hospital | Chicago | Illinois |
United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
United States | Children's Health Dallas University of Texas Southwestern | Dallas | Texas |
United States | University of Florida Congenital Heart Center | Gainesville | Florida |
United States | Joe DiMaggio Children's Hospital | Hollywood | Florida |
United States | Texas Children's Hospital | Houston | Texas |
United States | Loma Linda University | Loma Linda | California |
United States | Children's Hospital Los Angeles | Los Angeles | California |
United States | UCLA Mattel Children's Hospital | Los Angeles | California |
United States | Children's Hospital of Wisconsin | Milwaukee | Wisconsin |
United States | Children's Hospital of New York | New York | New York |
United States | Stanford University | Palo Alto | California |
United States | The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Phoenix Children's Hospital | Phoenix | Arizona |
United States | Children's Hospital of Pittsburgh of University of Pittsburgh School of Medicine | Pittsburgh | Pennsylvania |
United States | Washington University in St. Louis School of Medicine | Saint Louis | Missouri |
United States | Primary Children's Hospital | Salt Lake City | Utah |
United States | Seattle Children's Hospital | Seattle | Washington |
United States | Children's National Medical Center | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Boston Children's Hospital | Stanford University, United States Department of Defense |
United States,
Almond CS, Hoen H, Rossano JW, Castleberry C, Auerbach SR, Yang L, Lal AK, Everitt MD, Fenton M, Hollander SA, Pahl E, Pruitt E, Rosenthal DN, McElhinney DB, Daly KP, Desai M; Pediatric Heart Transplant Study (PHTS) Group Registry. Development and validation of a major adverse transplant event (MATE) score to predict late graft loss in pediatric heart transplantation. J Heart Lung Transplant. 2018 Apr;37(4):441-450. doi: 10.1016/j.healun.2017.03.013. Epub 2017 Mar 24. — View Citation
Almond CS, Sleeper LA, Rossano JW, Bock MJ, Pahl E, Auerbach S, Lal A, Hollander SA, Miyamoto SD, Castleberry C, Lee J, Barkoff LM, Gonzales S, Klein G, Daly KP. The teammate trial: Study design and rationale tacrolimus and everolimus against tacrolimus and MMF in pediatric heart transplantation using the major adverse transplant event (MATE) score. Am Heart J. 2023 Jun;260:100-112. doi: 10.1016/j.ahj.2023.02.002. Epub 2023 Feb 23. — View Citation
Castleberry C, Ziniel S, Almond C, Auerbach S, Hollander SA, Lal AK, Fenton M, Pahl E, Rossano JW, Everitt MD, Daly KP. Clinical practice patterns are relatively uniform between pediatric heart transplant centers: A survey-based assessment. Pediatr Transplant. 2017 Aug;21(5). doi: 10.1111/petr.13013. Epub 2017 Jul 3. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | EFFICACY: MATE-3 Score | MATE-3 is a validated score ranging from 0 to 12. The score represents the cumulative burden of three major adverse transplant events: Coronary Artery Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR) | 30 months post-randomization | |
Primary | SAFETY: MATE-6 Score | MATE-6 is a validated score ranging from 0 to 24. The score represents the cumulative burden of all six major adverse transplant events: Coronary Artery Vasculopathy (CAV), Chronic Kidney Disease (CKD), Biopsy-proven Acute Cellular Rejection (ACR), pathologic diagnosis of Antibody-Mediated Rejection (AMR), Infection, and Post-Transplant Lymphoproliferative Disorder (PTLD) | 30 months post-randomization | |
Secondary | Efficacy: Overall patient survival | Freedom from death from any cause | Up to 30 months post-randomization | |
Secondary | Efficacy: Overall allograft survival | Freedom from death and re-transplantation | Up to 30 months post-randomization | |
Secondary | Efficacy: Change in kidney function | Change in estimated glomerular filtration rate (eGFR) using the modified Schwartz equation | 0 to 6 months, 0 to 12 months, 0 to 30 months post-randomization | |
Secondary | Efficacy: Freedom from CKD event | Chronic Kidney Disease (CKD) | Follow-up through 30 months post-randomization | |
Secondary | Efficacy: Freedom from CAV event | Coronary Artery Vasculopathy (CAV) | Follow-up through 30 months post-randomization | |
Secondary | Efficacy: Freedom from BP-ACR event | Biopsy-proven Acute Cellular Rejection (ACR) | Follow-up through 30 months post-randomization | |
Secondary | Efficacy: Freedom from composite failure | The qualifying event is the earliest occurrence of death, graft loss, 2R/3R ACR rejection or rejection with HD | Follow-up through 30 months post-randomization | |
Secondary | Efficacy: Lansky and Karnofsky scores | Validated functional performance score, assigned by clinician assessment: Lansky score if < 16 years at randomization; Karnofsky if >=16 years at randomization | 18 and 30 months post-randomization | |
Secondary | Efficacy: EuroQOL EQ-5D Y (Youth Version) | Completed by study participant except for: EQ-5D-Y Proxy version will be used for children = 4 years but less than 8 years at randomization or children = 8 years who are unable to complete the EQ-5D-Y. | 18 and 30 months post-randomization | |
Secondary | Safety: Freedom from AMR | Pathologic diagnosis of Antibody-Mediated Rejection (AMR) | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from infection | Infection | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from PTLD | Post-Transplant Lymphoproliferative Disorder (PTLD) | Follow-up through 30 months post-randomization | |
Secondary | Safety: Frequency and incidence of adverse events including, but not limited to, hyperlipidemia, anemia, thrombocytopenia, interstitial lung disease, aphthous stomatitis, proteinuria, and rash | These AEs will be reported as individual endpoints as well as a composite. | Follow up through 30 months post-randomization | |
Secondary | Safety: Freedom from Major Transplant Events (Composite) | The qualifying event is the earliest occurrence of CKD, CAV, ACR, AMR, infection, and PTLD | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from Level 2 severity CKD Event | Chronic Kidney Disease | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from Level 2 severity CAV Event | Coronary artery vasculopathy | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from Level 2 severity ACR Event | Biopsy-proven Acute Cellular Rejection | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from Level 2 severity AMR Event | Pathologic diagnosis of Antibody-Mediated Rejection | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from Level 2 severity Infection Event | Infection | Follow-up through 30 months post-randomization | |
Secondary | Safety: Freedom from Level 2 severity PTLD Event | Post-transplant Lymphoproliferative Disorder | Follow-up through 30 months post-randomization | |
Secondary | Efficacy: Freedom from composite of CAV, CKD, BP-ACR, or any CMV infection | The event is the earliest occurrence of CAV, MATE CKD, BP-ACR, or any CMV infection. | Follow-up through 30 months post-randomization | |
Secondary | Efficacy: Change in CKD stage | Change in chronic kidney disease stage where improvements in CKD stage can take on a negative value. | Baseline visit through 30 months post-randomization | |
Secondary | Efficacy: MATE-3 score where CKD score is calculated by change from baseline visit | MATE-3 score where the CKD score is the change in MATE-CKD score from baseline visit through 30 months post-randomization. | Baseline visit through 30 months post-randomization | |
Secondary | Efficacy: MATE-3 score where CKD score is replaced by change in CKD stage | MATE-3 score where the CKD score is replaced by change in CKD stage from baseline visit through 30 months post-randomization. | Baseline visit through 30 months post-randomization | |
Secondary | Efficacy: Composite score consisting of MATE CAV, MATE BP-ACR, change in MATE CKD score, and any CMV infection. | Efficacy: Composite score consisting of MATE CAV, MATE BP-ACR, change in MATE CKD score from baseline visit, and any CMV infection. | Baseline visit through 30 months post-randomization | |
Secondary | Efficacy: Composite score consisting of MATE CAV, MATE BP-ACR, change in CKD stage, and any CMV infection. | Efficacy: Composite score consisting of MATE CAV, MATE BP-ACR, change in CKD stage from baseline visit, and any CMV infection. | Baseline visit through 30 months post-randomization |
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