Everolimus in de Novo Heart Transplant Recipients (EVERHEART)

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: November 19, 2009
Last updated: December 23, 2014
Last verified: December 2014
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.

Condition Intervention Phase
Cardiac Transplantation
Drug: Everolimus
Drug: Mycophenolate mofetil + Everolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Early vs. Delayed EVERolimus in de Novo HEART Transplant Recipients: Optimization of the Safety/Efficacy Profile (EVERHEART Study)

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Participants With at Least One Occurrence of Safety Composite Endpoint After 6 Months by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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

Secondary Outcome Measures:
  • Partcipants With at Least One Occurrence of Each Safety Composite Endpoint Event After 6 Months by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Hazard Cox's Model Analysis of Pericardial/Pleural Effusions [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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

  • Absolute and Percent Frequencies of Patients With LDL ≥ 100 mg/mL at 1, 3 and 6 Months, by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    LDL = low density lipoprotein

  • Participants With CMV Infection and CMV Syndrome/Disease After 6 Months by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    CMV infection is defined as pp65 antigenemia or DNAemia

  • Participants With at Least One Occurrence of Composite Treatment Failure Events [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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

Enrollment: 182
Study Start Date: September 2009
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Immediate introduction of everolimus Drug: Everolimus
Experimental: Delayed introduction of everolimus
delayed introduction) + Cyclosporin + steroids
Drug: Mycophenolate mofetil + Everolimus


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017029

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

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01017029     History of Changes
Other Study ID Numbers: CRAD001AIT16, 2009-011008-43
Study First Received: November 19, 2009
Results First Received: December 10, 2014
Last Updated: December 23, 2014
Health Authority: United States: Food and Drug Administration
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2015