Tacrolimus and Everolimus Against Mycophenolate Mofetil to Prevent Major Adverse Transplant Events in Pediatric Heart Transplant - TEAMMATE

Nov 12, 2023
Font Size
A
A
A
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Trial Sponsor:
US Department of Defense
Date Presented:
11/11/2023
Date Updated:
11/12/2023
Original Posted Date:
11/12/2023
References

Contribution To Literature:

The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given ≥6 months after cardiac transplantation.

Description:

The goal of the trial was to evaluate everolimus with low-dose tacrolimus compared with tacrolimus with mycophenolate among young patients who were ≥6 months after cardiac transplantation. The Food and Drug Administration previously issued a black box warning when everolimus was used within 3 months of cardiac transplant. The warning was due to a higher risk of mortality due to early infection.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Open-label

Children and young adults after cardiac transplant were randomized to everolimus with low-dose tacrolimus (n = 107) vs. tacrolimus with mycophenolate (n = 104).

  • Total number of enrollees: 211
  • Duration of follow-up: 30 months
  • Mean patient age: 7 years
  • Percentage female: 50%

Inclusion criteria:

  • Cardiac transplantation at age ≤21 years
  • ≥6 months after heart transplantation
  • Stable immunosuppression

Exclusion criteria:

  • Recurrent rejection/graft dysfunction
  • Steroid dose >0.1 mg/kg/day
  • Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2
  • Active infection or wound healing problem
  • Severe hyperlipidemia or proteinuria

Principal Findings:

The primary efficacy outcome was defined by the major adverse transplant event (MATE) score (points assigned for each of the following; cardiac allograft vasculopathy, renal dysfunction, acute cellular rejection, antibody-mediated rejection, infection, or post-transplant lymphoproliferative disorder). MATE-6 considered all of these outcomes, while MATE-3 considered cardiac allograft vasculopathy, renal dysfunction, acute cellular rejection.

  • The co-primary outcome, median MATE-6 score at 30 months, was 1.96 in the everolimus group vs. 2.18 in the tacrolimus group (p = not significant [NS]).
  • The co-primary outcome, median MATE-3 score at 30 months, was 0.93 in the everolimus group vs. 1.25 in the tacrolimus group (p = NS).

Secondary outcomes:

  • Of the MATE-6 components, the everolimus group had numerically lower cardiac allograft vasculopathy, renal dysfunction, and rejection. The everolimus group had numerically higher infection and lymphoproliferative disorder.
  • Of the MATE-3 components, the everolimus group had numerically lower cardiac allograft vasculopathy, and renal dysfunction. The everolimus group had numerically higher cellular rejection.
  • Median MATE-3 score + cytomegalovirus infection at 30 days: 1.06 in the everolimus group vs. 1.51 in the tacrolimus group (p = 0.03)
  • eGFR was higher in the everolimus vs. tacrolimus group (p < 0.05)
  • Percentage with anti-HLA antibodies was lower in the everolimus vs. tacrolimus group (p < 0.05)
  • Drug discontinuation due to adverse event: 12% with everolimus vs. 21% with tacrolimus (p < 0.001)

Interpretation:

Among children and young adults with cardiac transplantation, everolimus with low-dose tacrolimus compared with tacrolimus with mycophenolate was safe when initiated 6 months after cardiac transplant. In the present trial, everolimus with low-dose tacrolimus was also associated with higher eGFR and lower anti-HLA antibody compared with tacrolimus with mycophenolate.

References:

Presented by Dr. Christopher Almond at the American Heart Association Scientific Sessions, Philadelphia, PA, November 11, 2023.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Heart Transplant, Cardiac Surgery and CHD and Pediatrics

Keywords: AHA23, Heart Transplantation, Immunosuppression Therapy, Pediatric Cardiology


< Back to Listings