Efficacy and Safety of Everolimus in Recipients of Heart Transplants to Prevent Acute and Chronic Rejection
A 24-month, Multi-center, Randomized, Open-label, Non-inferiority Study of Efficacy and Safety Comparing Two Exposures of Concentration-controlled Everolimus With Reduced Cyclosporine Versus 3.0 g Mycophenolate Mofetil With Standard Dose Cyclosporine in de Novo Heart Transplant Recipients
1 other identifier
interventional
721
14 countries
63
Brief Summary
This trial was to examine the impact of everolimus and reduced dose of cyclosporine on efficacy and safety compared to mycophenolate mofetil and a standard dose of cyclosporine in heart transplant recipients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2006
Longer than P75 for phase_3
63 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2006
CompletedFirst Submitted
Initial submission to the registry
March 6, 2006
CompletedFirst Posted
Study publicly available on registry
March 8, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2011
CompletedResults Posted
Study results publicly available
August 16, 2012
CompletedAugust 16, 2012
July 1, 2012
5.5 years
March 6, 2006
July 6, 2012
July 10, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Composite Efficacy Failure at 12 Months
Composite efficacy failure was defined as Biopsy Proven Acute Rejection(BPAR) of International Society for Heart and Lung Transplantation(ISHLT) grade ≥3A, Acute Rejection associated with Hemodynamic Compromise, Graft loss/Retransplant, Death or Loss to follow-up. Identification of acute rejection was based on the local pathologist's evaluation of endomyocardial biopsy slides. Hemodynamic compromise was present if 1 or more of the following were met: Ejection fraction ≤30% or 25% lower than Baseline or Fractional shortening ≤20% or 25% lower than Baseline and/or use of inotropic treatment.
12 Months
Secondary Outcomes (9)
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months
12 Months
Renal Function Measured by Glomerular Filtration Rate (GFR) at 12 Months
12 Months
Change From Baseline in the Average Maximum Intimal Thickness at Month 12
Baseline, Month 12
Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12
12 Months
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR of ISHLT Grade ≥ 3A), Acute Rejection Associated With Hemodynamic Compromise (HDC), Graft Loss/Re-transplant and Death at Month 12
12 Months
- +4 more secondary outcomes
Study Arms (3)
everolimus 1.5 mg
EXPERIMENTALWithin 72 hours after transplantation participants received 0.75 mg everolimus tablets twice a day 12 hours apart for a total 1.5 mg daily dose in combination with reduced cyclosporine and standard dose corticosteroids for 24 months. The everolimus dose could be adjusted to maintain a target everolimus trough level of 3-8 ng/mL.
everolimus 3.0 mg
EXPERIMENTALWithin 72 hours after transplantation participants received 1.5 mg everolimus tablets twice a day 12 hours apart for a total 3.0 mg daily dose in combination with reduced cyclosporine and standard dose corticosteroids for 24 months. The everolimus dose could be adjusted to maintain a target everolimus trough level of 6-12 ng/mL. Randomization of new patients in this arm was prematurely stopped as of 27 March 2008 due to high mortality rate, as per Data Monitoring Committee.
mycophenolate mofetil
ACTIVE COMPARATORWithin 72 hours after transplantation participants received 3 tablets 500 mg mycophenolate mofetil twice a day 12 hours apart for a total daily dose of 3000 mg in combination with a standard cyclosporine dose and standard dose corticosteroids for 24 months.
Interventions
Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.
Mycophenolate mofetil supplied as 500 mg tablets.
Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.
Corticosteroids standard dose.
Eligibility Criteria
You may qualify if:
- Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation.
- The graft must be functional at time of randomization.
You may not qualify if:
- Patients who are recipients of multiple solid organ transplants or tissue transplants or have previously received organ transplants.
- Patients who are recipients of ABO incompatible transplants.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (64)
UCLA Medical Center
Los Angeles, California, United States
California Pacific Medical Center
San Francisco, California, United States
Stanford U Sch, Falk Cardiovasular Research Ctr.
Stanford, California, United States
University of Florida Shands Hospital
Gainesville, Florida, United States
Emory University Hospital
Atlanta, Georgia, United States
Loyola Univerisity Medical School
Maywood, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Tufts Medical Center
Boston, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
Columbia University Medical Center
New York, New York, United States
Recanati Miller Transplant Institute
New York, New York, United States
UNC Division of Cardiology
Chapel Hill, North Carolina, United States
Duke University Heart Failure Research
Durham, North Carolina, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Penn State College of Medicine
Hershey, Pennsylvania, United States
Hahnemann University Hospital
Philadelphia, Pennsylvania, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Texas Cardiovascular Consultants
Austin, Texas, United States
University of Texas Medical Branch, Div of Cardio Thoracic
Galveston, Texas, United States
Methodist Hospital/DeBakey Heart Failure Research Center
Houston, Texas, 77030, United States
Intermountain Medical Center
Murray, Utah, United States
University of Wisconsin - Madison Medical School
Madison, Wisconsin, 53792, United States
St. Luke's Medical Center Cardiac Services
Milwakee, Wisconsin, United States
Sanatorio Parque
Rosario, Santa Fe Province, Argentina
Fundacion Favalaro
Buenos Aires, Argentina
St Vincents Hospital
Darlinghurst, New South Wales, Australia
Prince Charles Hospital
Chermside, Queensland, Australia
Royal Perth Hospital
Perth, Western Australia, Australia
Universitaet Wien
Vienna, Austria
Cliniques Universitaires Saint-Luc
Brussels, Belgium
University of Alberta Hospital
Edmonton, Alberta, Canada
St Paul's Hospital
Vancouver, British Columbia, Canada
New Halifax Infirmary
Halifax, Nova Scotia, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Institut Univ. de cardiologie et pneumologie de Quebec
Sainte-Foy, Quebec, Canada
Hopital Cardiologique de Lyon
Lyon, France
Hopital Georges Pompidou
Paris, France
Hopital Pitie Salpetriere
Paris, France
CHU de Strasbourg Hopital Civil Medicale B
Strasbourg, France
CHU Hopital de Brabois
Vandœuvre-lès-Nancy, France
Herz- u. Diabeteszentrum NRW/Ruhr-Univ. Bochum
Bad Oeynhausen, Germany
Deutsches Herzzentrum Berlin
Berlin, Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, Germany
Kliniken der Med. Hochschule
Hanover, Germany
Universitaetsklinikum Kiel
Kiel, Germany
Universitaetsklinik Regensburg
Regensburg, Germany
Az. Osp. di Bologna Policl. S. Orsola-Malpighi Univ. degli Studi
Bologna, Italy
Azienda Ospedaliera G. Brotzu
Cagliari, Italy
A.O.-Universita di Padova-Universita degli Studi
Padua, Italy
Fodazione IRCCS Policlinico S. Matteo
Pavia, Italy
Azienda Ospedaliera S. Camillo-Forlanini
Roma, Italy
Az. Ospedaliero-Universitaria S. Giovanni Battista di Torino
Torino, Italy
Auckland Hospital
Auckland, New Zealand
Rikshospitalet, Hjertemedisinskavdeling
Oslo, Norway
Cardiovascular Center of Puerto Rico and the Caribbean
San Juan, Puerto Rico
Hospital Universitario Reina Sofia
Córdoba, Spain
Hospital Puerta de Hierro Majadahonda
Madrid, Spain
National Taiwan University Hospital
Taipei, Taiwan
Queen Elizabeth Hospital
Birmingham, United Kingdom
Papworth Hospital
Cambridge, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis
Novartis
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 6, 2006
First Posted
March 8, 2006
Study Start
January 1, 2006
Primary Completion
July 1, 2011
Study Completion
July 1, 2011
Last Updated
August 16, 2012
Results First Posted
August 16, 2012
Record last verified: 2012-07