Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score (TEAMMATE)

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Post-transplant Lymphoproliferative Disorder; Immunosuppression; Pediatric Heart Transplantation; Cardiac Allograft Vasculopathy; Heart Transplant Failure and Rejection; Heart Transplant Infection
• Intervention / Treatment: Drug: Everolimus; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Detailed Description

Median survival after pediatric heart transplantation (HT) is 15 years in the current era. This means that a substantial fraction of patients transplanted during childhood fail to survive to adulthood, or require heart re-transplantation, because of complications related to heart transplant. These complications include heart transplant rejection, infection, coronary artery disease, post-transplant lymphoproliferative disorder (PTLD; a form of lymphoma seen in transplant recipients), and kidney failure. Most complications stem not from the heart transplant itself, but from the drugs commonly used to suppress the immune system in order to prevent rejection. In the US, tacrolimus (TAC) and mycophenolate mofetil (MMF), have emerged over the past decade as the standard of care for pediatric heart transplant immunosuppression. While pediatric survival has improved significantly in the era of TAC and MMF, post-HT complications remain a major problem that limits median survival to 15 years. Recently, everolimus (EVL) has emerged as a potential alternative immunosuppressant that may prevent rejection, coronary artery disease and kidney failure more effectively than TAC/MMF when administered in combination with low-dose tacrolimus (LDTAC). Preliminary studies suggest that EVL, and its first-generation analog sirolimus, are well tolerated in children after HT, regardless of whether it is started in response to coronary artery disease, in response to chronic kidney disease, or empirically 4-6 months after transplant in an effort to prevent the development of these complications1. However, studies are generally limited to single-center experiences using historical controls and have inadequate statistical power to demonstrate treatment differences. This will be the first multicenter randomized clinical trial of maintenance immunosuppression in pediatric heart transplantation to systematically evaluate the safety and efficacy of EVL with LDTAC vs. TAC/MMF to prevent long-term complications which lead to death/graft loss. The major adverse transplant event (MATE) score will serve as the primary endpoint to power the trial. Because no Food & Drug Administration (FDA)-approved immunosuppressants currently exist for children after heart transplant (all prescriptions are off-label) and market incentives to support a trial are limited, the investigators have funded the trial through a Fiscal Year 2016 Peer Reviewed Medical Research Program Clinical Trial Award sponsored by the Department of Defense office of the Congressionally Directed Medical Research Programs. It is worth noting that in contrast to adults, children have a substantially longer potential life expectancy if post-transplant complications can be minimized, making the prevention of late complications an urgent priority for the pediatric heart transplant community.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90095
      • UCLA Mattel Children's Hospital
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-0297
      • University of Florida Congenital Heart Center
    • Hollywood, Florida, United States, 33021
      • Joe DiMaggio Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta Emory
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University in St. Louis School of Medicine
  • New York
    • New York, New York, United States, 10032
      • Children's Hospital of New York
    • The Bronx, New York, United States, 10803
      • Children's Hospital at Montefiore
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of University of Pittsburgh School of Medicine
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Health Dallas University of Texas Southwestern
    • Houston, Texas, United States, 77027
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus/Low-Dose Tacrolimus; Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml. Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)	Drug: Everolimus; Everolimus tablet; Other Names: Zortress; Drug: Tacrolimus; Tacrolimus capsule or liquid suspension; Other Names: Prograf
Active Comparator: Tacrolimus/Mycophenolate Mofetil; Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.) Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.	Drug: Tacrolimus; Tacrolimus capsule or liquid suspension; Other Names: Prograf; Drug: Mycophenolate Mofetil; Mycophenolate Mofetil capsule or liquid suspension; Other Names: Cellcept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFFICACY: MATE-3 Score	MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). Complete details of the score can be found in the study protocol. A higher score represents a worse outcome.	30 months post-randomization
SAFETY: MATE-6 Score	MATE-6 is a validated score ranging from 0 to 24. The score adds together each subscore so that it 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). Complete details of the score can be found in the study protocol. A higher score represents a worse outcome.	30 months post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Overall Patient Survival	Number of participants who experienced death from any cause	Up to 30 months post-randomization
Efficacy: Overall Allograft Survival	Number of participants who experienced death or heart re-transplantation	Up to 30 months post-randomization
Efficacy: Change in Kidney Function	Change in estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. A positive number indicates improved kidney function, a negative number indicates worsened kidney function.	0 to 6 months, 0 to 12 months, 0 to 30 months post-randomization
Efficacy: Freedom From CKD Event	Number of participants who are "free from" (have NOT experienced) a chronic kidney disease MATE. A chronic kidney disease MATE was defined as an eGFR < 60 ml/min/1.73 m^2 during follow-up or worsening by at least one MATE score if < 60 ml/min/1.73 m^2 at baseline. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Efficacy: Freedom From CAV Event	Number of participants who are "free from" (have NOT experienced) cardiac allograft vasculopathy (CAV) during follow up as graded by the angiography core laboratory. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Efficacy: Freedom From BP-ACR Event	Number of participants who are "free from" (have NOT experienced) biopsy-proven Acute Cellular Rejection (ACR) MATE event during follow-up. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Efficacy: Freedom From Composite Failure	Number of participants who are "free from" (have NOT experienced) the composite of death, graft loss, 2R/3R acute cellular rejection or rejection with hemodynamic compromise. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Efficacy: EuroQOL EQ-5D Y (Youth Version)	The EuroQOL EQ-5D Y uses a visual-analog scale and asks the participant to mark an X on the line to show how good or bad your is health TODAY. The scale ranges from 0 to 100.	30 months post-randomization
Safety: Freedom From AMR	Number of participants who are "free from" (have NOT experienced) a pathologic diagnosis of Antibody-Mediated Rejection (AMR) MATE Event. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Infection	Number of participants who are "free from" (have NOT experienced) a serious infection MATE during follow-up. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From PTLD	Number of participants who are "free from" (have NOT experienced) a Post-Transplant Lymphoproliferative Disorder (PTLD) MATE event during follow-up. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Number of Participants Experiencing Adverse Events	Adverse events reported throughout the study. Adverse events are classified by CTCAE classification. Serious adverse events include CTCAE classes 3, 4, and 5.	From enrollment to 30 months after enrollment
Safety: Freedom From Major Transplant Events (Composite)	Number of participants who are "free from" (have NOT experienced) any MATE event, this includes chronic kidney disease, cardiac allograft vasculopathy, acute cellular rejection, antibody mediated rejection, serious infection, and post-transplant lymphoproliferative disease. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Grade 2 or Greater Severity CKD Event	Number of participants who are "free from" (have NOT experienced) a chronic kidney disease MATE of Grade 2 or greater (eGFR <45 ml/min/1.73 m^2 or on dialysis) or death due to chronic kidney disease. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Grade 2 or Greater Severity CAV Event	Number of participants who are "free from" (have NOT experienced) a cardiac allograft vasculopathy MATE of Grade 2 or greater. Grade 2 or greater is the same as having International Society of Heart and Lung Transplantation cardiac allograft vasculopathy Grade 2 or 3 or death due to cardiac allograft vasculopathy. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Grade 2 or Greater Severity ACR Event	Number of participants who are "free from" (have NOT experienced) an acute cellular rejection MATE of Grade 2 or greater. Grade 2 or greater is the equivalent of treated rejection with an assigned International Society of Heart & Lung Transplantation acute cellular rejection grade 2 or grade 3 or rejection with hemodynamic compromise (decreased ejection fraction, need for IV medicine to support heart, need for mechanical circulatory support) or death due to acute cellular rejection. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Grade 2 or Greater Severity AMR Event	Number of participants who are "free from" (have NOT experienced) an antibody mediated rejection MATE of Grade 2 or greater. Grade 2 or greater is the equivalent of treated rejection with an assigned International Society of Heart & Lung Transplantation antibody mediated rejection grade 2 or grade 3 or antibody mediated rejection with hemodynamic compromise (decreased ejection fraction, need for IV medicine to support heart, need for mechanical circulatory support) or death due to antibody mediated rejection. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Grade 2 or Greater Severity Infection Event	Number of participants who are "free from" (have NOT experienced) a serious infection MATE of Grade 2 or greater. Grade 2 infections require treatment with intravenous antibiotics or antivirals for 5 or more days. Grade 3 includes treatment of sepsis, endocarditis, invasive infection, or infection leading to respiratory failure. Grade 4 is death due to infection. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Safety: Freedom From Grade 2 or Greater Severity PTLD Event	Number of participants who are "free from" (have NOT experienced) a post-transplant lymphoproliferative disease MATE of Grade 2 or greater. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
Efficacy: Freedom From Composite of CAV, CKD, BP-ACR, or Any CMV Infection	Number of participants who are "free from" (have NOT experienced) at least one of cardiac allograft vasculopathy, chronic kidney disease with estimated glomerular filtration rate less than or equal to 60 ml/min/1.73m2, treated acute cellular rejection, or any cytomegalovirus infection. A higher number of participants on this measure indicates a better outcome.	From enrollment to 30 months after enrollment
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
Efficacy: MATE-3 Score Where CKD Score is Calculated by Change From Baseline Visit	MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). For this version of the score, the chronic kidney disease score is replaced by the change in MATE-CKD score from baseline visit through 30 months post-randomization. CKD change score can assume a negative value. This modified score can range from -2 to 12. A higher score represents a worse outcome.	Baseline visit through 30 months post-randomization
Efficacy: MATE-3 Score Where CKD Score is Replaced by Change in CKD Stage	MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). For this version of the score, the chronic kidney disease score is replaced by the change in chronic kidney disease stage from the baseline visit through 30 months post-randomization. Chronic kidney disease stage change score can assume a negative value. This modified score can range from -2 to 12. A higher score represents a worse outcome.	Baseline visit through 30 months post-randomization
Efficacy: Composite Score Consisting of MATE CAV, MATE BP-ACR, MATE CKD Score, and Any CMV Infection.	Composite score ranging from 0 to 16. The score adds each subscore to represent the cumulative burden of three major adverse transplant events plus CMV infection. The three major adverse transplant events are Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). Any CMV infection is assigned a score of 1 with additional points using the MATE infection scoring criteria. Full details of the score can be found in the protocol. A higher score represents a worse outcome.	Baseline visit through 30 months post-randomization
Efficacy: Composite Score Consisting of MATE CAV, MATE BP-ACR, Change in CKD Stage, and Any CMV Infection.	Composite score ranging from -2 to 16. The score adds each subscore to represent the cumulative burden of Cardiac Allograft Vasculopathy (CAV), chronic kidney disease, and Biopsy-proven Acute Cellular Rejection (ACR). Any CMV infection is assigned a score of 1 with additional points using the MATE infection scoring criteria. The chronic kidney disease MATE score is replaced by change in CKD stage. A higher score represents a worse outcome.	Baseline visit through 30 months post-randomization
Efficacy: Lansky Scores	Validated functional performance score, assigned by clinician assessment: Lansky score is assigned if < 16 years old at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.	Baseline
Efficacy: Lansky Scores	Validated functional performance score, assigned by clinician assessment: Lansky score is assigned if < 16 years old at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.	18 months post-randomization
Efficacy: Lansky Scores	Validated functional performance score, assigned by clinician assessment: Lansky score is assigned if < 16 years old at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.	30 months post-randomization
Efficacy: Karnofsky Scores	Validated functional performance score, assigned by clinician assessment: Karnofsky score is assigned if >=16 years at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.	Baseline
Efficacy: Karnofsky Scores	Validated functional performance score, assigned by clinician assessment: Karnofsky score is assigned if >=16 years at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.	18 months post-randomization
Efficacy: Karnofsky Scores	Validated functional performance score, assigned by clinician assessment: Karnofsky score is assigned if >=16 years at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.	30 months post-randomization

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: United States Department of Defense; Stanford University
• Investigators: Study Chair: Christopher S Almond, MD, MPH, Stanford University; Study Chair: Kevin P Daly, MD, Boston Children's Hospital; Principal Investigator: Lynn A Sleeper, ScD, Boston Children's Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• Grimm K, Lehner A, Fernandez Rodriguez S, Orban M, Fischer M, Rosenthal LL, Jakob A, Haas NA, Dalla Pozza R, Kozlik-Feldmann R, Ulrich SM. Conversion to everolimus in pediatric heart transplant recipients is a safe treatment option with an impact on cardiac allograft vasculopathy and renal function. Clin Transplant. 2021 Mar;35(3):e14191. doi: 10.1111/ctr.14191. Epub 2020 Dec 30.
• 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.
• Almond CS, Daly KP, Albers EL, Alejos JC, Ameduri R, Auerbach SR, Barkoff L, Barnes AP, Bock MJ, Butto A, Carlo WF, Castleberry CD, Chrisant MR, Deshpande SR, Dreyer WJ, Everitt MD, Feingold B, Gonzales S, Hollander SA, Kindel SJ, Klein GL, Lal AK, Lamour JM, Lee J, Lu M, Lytrivi ID, Miyamoto SD, Pahl E, Peng DM, Ryan TD, Singh TP, Su JA, Sutcliffe DL, Ybarra AM, Zangwill S, Rossano JW, Sleeper LA; TEAMMATE Trial Investigators. Everolimus and Low-Dose Tacrolimus After Heart Transplant in Children: A Randomized Clinical Trial. JAMA. 2025 Oct 21;334(15):1339-1348. doi: 10.1001/jama.2025.14338.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2018
• Primary Completion (Actual): April 17, 2023
• Study Completion (Actual): May 17, 2023

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): July 31, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: children; everolimus; mycophenolate mofetil; randomized clinical trial; heart transplantation; tacrolimus
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Behavior; Social Behavior; Renal Insufficiency, Chronic; Rejection, Psychology; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Macrolides; Lactones; Sirolimus; Caproates; Everolimus; Mycophenolic Acid; Tacrolimus
• Other Study ID Numbers: P00025970; PR160574 (Other Grant/Funding Number: U.S. Department of Defense); IND 127980 (Other Identifier: Food and Drug Administration)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No