Principal Investigator: Ashwin Lal
Keywords: pediatric heart transplant Department: Department of Pediatrics
IRB Number: 00106833
Specialty: Pediatric Cardiology
Sub Specialties:
Recruitment Status: Active, not recruiting

Contact Information

Linda Lambert
linda.lambert@hsc.utah.edu
801 587 7523

Simple Summary

Efficacy: To test the hypothesis that among children who survive to 6 months post-heart transplantation (HT), those randomized to everolimus and low-dose tacrolimus (EVL/LDTAC) for 30 months will have a lower total burden of three major adverse transplant events: cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and biopsy-proven acute cellular rejection (BP-ACR), as defined by the MATE-3 score, compared to children randomized to standard therapy with tacrolimus and mycophenolate mofetil (TAC/MMF).Safety: To test the hypothesis that among children who survive to 6 months post-HT, those randomized EVL/LDTAC for 30 months will not have a higher risk of graft loss due to all causes as defined by the MATE-6 score, compared to children randomized to standard therapy with TAC/MMF.Medication Tolerability: To determine the tolerability of EVL/LDTAC compared to TAC/MMF for prevention of major post-transplant complications by characterizing the frequency and incidence of AEs that are at least possibly related to everolimus and low-dose tacrolimus or TAC/MMF.

Inclusion Criteria

1. Orthotopic heart transplantation performed 5-7 months prior to randomization
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) or waitlisted for a non-heart organ transplant.

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-HT.

5.       Graft dysfunction (LVEF <40% or Wedge >22 mmHg or CI <2.2 L/min/m2)

6.       Stage 4 or 5 CKD (eGFR <30 ml/min/1.73m2)

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 are confirmed.

11.   Uncontrolled diabetes mellitus.

12.   Diagnosis of PTLD during the first 6 months post-HT.

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 (see Table 5-7).

15.   Patients who are pregnant or breast-feeding or intend to get pregnant during the study period.

 

Participant Reimbursement

You will be paid $50.00 per visit after completion of Research Visits 1-7. You will be paid $100 when you complete the final study visit (Visit 8).This will add up to a total of $450.00 if you complete all of the research visits. This money will be a token for your time, transportation costs, and meals.