Everolimus in de Novo Heart Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study, in de novo heart transplant patients, is to evaluate whether delayed introduction of everolimus reduces the occurrence of wound healing problems, pericardial and/or pleural effusion and early acute renal insufficiency, as compared with immediate introduction of everolimus, in the firs six months after heart transplantation.

Official Title
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Early vs. Delayed EVERolimus in de Novo HEART Transplant Recipients: Optimization of the Safety/Efficacy Profile (EVERHEART Study)

Conditions
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Cardiac Transplantation

Intervention / Treatment
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* Drug: Everolimus
* Drug: Mycophenolate mofetil + Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female cardiac transplant candidates 18-65 years of age undergoing primary heart transplantation. Glomerular filtration rate (GFR by MDRD) ≥ 40 mL/min/1.73 m2 at randomization Exclusion criteria: Patients who are recipients of multiple solid organ transplants Patients who are HIV-positive or Hepatitis C positive (PCR only) or B-surface antigen positive; Presence of Donor/Recipients serological mismatch for Hepatitis B or C; Recipients of organ from donors positive for Hepatitis B-surface antigen; Panel Reactive Antibodies (cytotoxicity method) > 30%. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate introduction of everolimus<br> | Drug: Everolimus<br> <br> |
| Experimental: Delayed introduction of everolimus<br>delayed introduction) + Cyclosporin + steroids | Drug: Mycophenolate mofetil + Everolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group | Comparison of 6-month cumulative incidence of safety composite endpoint (wound healing delay) related to initial transplant surgery, pleural/pericardial effusions and occurrence of acute renal insufficiency, defined as estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2, between delayed everolimus arm and immediate everolimus arm | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partcipants With at Least One Occurrence of Each Safety Composite Endpoint Event After 6 Months by Treatment Group |  | 6 months | 
| Hazard Cox's Model Analysis of Pericardial/Pleural Effusions | Pericardial effusions: any pericardial effusion defined as at least moderate (i.e. measuring at least 2.0 cm in diastole, in the point of largest distance between the pericardial leaflets), with or without signs of hemodynamic compromise, or leading to drainage or to prolonged hospitalization. Pleural effusions: need for surgical drainage tubes for longer than 7 days after surgery and subsequent pleural effusions leading to drainage. CI = confidence interval, HR = hazard ratio, MDRD = Modification of Diet in Renal Disease | 6 months | 
| Absolute and Percent Frequencies of Patients With LDL ≥ 100 mg/mL at 1, 3 and 6 Months, by Treatment Group | LDL = low density lipoprotein | 6 months | 
| Participants With CMV Infection and CMV Syndrome/Disease After 6 Months by Treatment Group | CMV infection is defined as pp65 antigenemia or DNAemia | 6 months | 
| Participants With at Least One Occurrence of Composite Treatment Failure Events | Comparison of 6-months cumulative incidence of composite treatment failure events (BPAR ≥ 2R, rejection with hemodynamic compromise, graft loss, or death) between delayed everolimus arm and immediate everolimus arm | 6 months |