Everolimus in de Novo Heart Transplant Recipients (EVERHEART)

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Transplantation
• Intervention / Treatment: Drug: Everolimus; Drug: Mycophenolate mofetil + Everolimus

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • BA
    • Bari, BA, Italy, 70124
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • CA
    • Cagliari, CA, Italy, 09134
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00152
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • UD
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Immediate introduction of everolimus	Drug: Everolimus
EXPERIMENTAL: Delayed introduction of everolimus; delayed introduction) + Cyclosporin + steroids	Drug: Mycophenolate mofetil + Everolimus

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Potena L, Pellegrini C, Grigioni F, Amarelli C, Livi U, Maccherini M, Masciocco G, Faggian G, Lilla Della Monica P, Gerosa G, Marraudino N, Corda M, Boffini M; EVERHEART Investigators. Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART. Transplantation. 2018 Mar;102(3):493-501. doi: 10.1097/TP.0000000000001945.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: November 19, 2009
• First Submitted That Met QC Criteria: November 19, 2009
• First Posted (ESTIMATE): November 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): January 12, 2015
• Last Update Submitted That Met QC Criteria: December 23, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Everolimus
• Other Study ID Numbers: CRAD001AIT16; 2009-011008-43