Last updated on March 2018

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

Brief description of study

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).

Detailed Study 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.

Clinical Study Identifier: NCT03386539

Contact Investigators or Research Sites near you

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Waldemar F Carlo, MD

Children's of Alabama
Birmingham, AL United States
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Steven Zangwill, MD

Phoenix Children's Hospital
Phoenix, AZ United States
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Matthew J Bock, MD

Loma Linda University
Loma Linda, CA United States
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Seth Hollander, MD

Stanford University
Palo Alto, CA United States
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Scott R Auerbach, MD

Children's Hospital Colorado
Aurora, CO United States
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Biago Pietra, MD

University of Florida Congenital Heart Center
Gainesville, FL United States
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Alfred Asante-Korang, MD

Johns Hopkins All Children's Hospital
Saint Petersburg, FL United States
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Shriprasad Deshpande, MD

Children's Healthcare of Atlanta Emory
Atlanta, GA United States
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Elfriede Pahl, MD

Lurie Children's Hospital
Chicago, IL United States
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Kevin P Daly, MD

Boston Children's Hospital
Boston, MA United States
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David Peng, MD

University of Michigan Medical Center
Ann Arbor, MI United States
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Chesney Castleberry, MD

Washington University in St. Louis School of Medicine
Saint Louis, MO United States
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Jacqueline M Lamour, MD

Children's Hospital at Montefiore
Bronx, NY United States
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Linda J Addonizio, MD

Children's Hospital of New York
New York, NY United States
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Thomas D Ryan, MD

Cincinnati Children's Hospital Medical Center
Cincinnati, OH United States
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Joseph Rossano, MD

The Children's Hospital of Philadelphia
Philadelphia, PA United States
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Briand D Feingold, MD

Children's Hospital of Pittsburgh of University of Pittsburgh School of Medicine
Pittsburgh, PA United States
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Heather Henderson, MD

Medical University of South Carolina
Charleston, SC United States
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David L Sutcliffe, MD

Children's Health Dallas University of Texas Southwestern
Dallas, TX United States
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William J Dreyer, MD

Texas Children's Hospital
Houston, TX United States
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Ashwin Lal, MD

Primary Children's Hospital
Salt Lake City, UT United States
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Steven Kindel, MD

Children's Hospital of Wisconsin
Milwaukee, WI United States
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Recruitment Status: Open

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