Efficacy and Safety of Everolimus in Recipients of Heart Transplants to Prevent Acute and Chronic Rejection

NCT ID: NCT00300274

Last Updated: 2012-08-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

721 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-01-31

Study Completion Date

2011-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Graft Rejection

Keywords

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Everolimus heart transplant heart disease transplantation heart IVUS assessment at 12 months rate of graft loss acute rejection episodes survival

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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everolimus 1.5 mg

Within 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.

Group Type EXPERIMENTAL

everolimus

Intervention Type DRUG

Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.

cyclosporine

Intervention Type DRUG

Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.

corticosteroids

Intervention Type DRUG

Corticosteroids standard dose.

everolimus 3.0 mg

Within 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.

Group Type EXPERIMENTAL

everolimus

Intervention Type DRUG

Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.

cyclosporine

Intervention Type DRUG

Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.

corticosteroids

Intervention Type DRUG

Corticosteroids standard dose.

mycophenolate mofetil

Within 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.

Group Type ACTIVE_COMPARATOR

mycophenolate mofetil

Intervention Type DRUG

Mycophenolate mofetil supplied as 500 mg tablets.

cyclosporine

Intervention Type DRUG

Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.

corticosteroids

Intervention Type DRUG

Corticosteroids standard dose.

Interventions

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everolimus

Everolimus supplied as 0.75 mg tablets. Everolimus was also supplied in 0.25 mg and 0.5 mg tablets for dose adjustments.

Intervention Type DRUG

mycophenolate mofetil

Mycophenolate mofetil supplied as 500 mg tablets.

Intervention Type DRUG

cyclosporine

Cyclosporine reduced dose in the everolimus arms (approximately half of the standard dose) and standard dose in the mycophenolate mofetil arm.

Intervention Type DRUG

corticosteroids

Corticosteroids standard dose.

Intervention Type DRUG

Other Intervention Names

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Zortress® Certican® Cellcept® Neoral®

Eligibility Criteria

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Inclusion Criteria

* Male or female cardiac recipients 18-70 years of age undergoing primary heart transplantation.
* The graft must be functional at time of randomization.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis

Role: STUDY_DIRECTOR

Novartis

Locations

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UCLA Medical Center

Los Angeles, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Stanford U Sch, Falk Cardiovasular Research Ctr.

Stanford, California, United States

Site Status

University of Florida Shands Hospital

Gainesville, Florida, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Loyola Univerisity Medical School

Maywood, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Recanati Miller Transplant Institute

New York, New York, United States

Site Status

UNC Division of Cardiology

Chapel Hill, North Carolina, United States

Site Status

Duke University Heart Failure Research

Durham, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Penn State College of Medicine

Hershey, Pennsylvania, United States

Site Status

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Texas Cardiovascular Consultants

Austin, Texas, United States

Site Status

University of Texas Medical Branch, Div of Cardio Thoracic

Galveston, Texas, United States

Site Status

Methodist Hospital/DeBakey Heart Failure Research Center

Houston, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

University of Wisconsin - Madison Medical School

Madison, Wisconsin, United States

Site Status

St. Luke's Medical Center Cardiac Services

Milwakee, Wisconsin, United States

Site Status

Sanatorio Parque

Rosario, Santa Fe Province, Argentina

Site Status

Fundacion Favalaro

Buenos Aires, , Argentina

Site Status

St Vincents Hospital

Darlinghurst, New South Wales, Australia

Site Status

Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Universitaet Wien

Vienna, , Austria

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

St Paul's Hospital

Vancouver, British Columbia, Canada

Site Status

New Halifax Infirmary

Halifax, Nova Scotia, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Institut Univ. de cardiologie et pneumologie de Quebec

Sainte-Foy, Quebec, Canada

Site Status

Hopital Cardiologique de Lyon

Lyon, , France

Site Status

Hopital Georges Pompidou

Paris, , France

Site Status

Hopital Pitie Salpetriere

Paris, , France

Site Status

CHU de Strasbourg Hopital Civil Medicale B

Strasbourg, , France

Site Status

CHU Hopital de Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Herz- u. Diabeteszentrum NRW/Ruhr-Univ. Bochum

Bad Oeynhausen, , Germany

Site Status

Deutsches Herzzentrum Berlin

Berlin, , Germany

Site Status

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Kliniken der Med. Hochschule

Hanover, , Germany

Site Status

Universitaetsklinikum Kiel

Kiel, , Germany

Site Status

Universitaetsklinik Regensburg

Regensburg, , Germany

Site Status

Az. Osp. di Bologna Policl. S. Orsola-Malpighi Univ. degli Studi

Bologna, , Italy

Site Status

Azienda Ospedaliera G. Brotzu

Cagliari, , Italy

Site Status

A.O.-Universita di Padova-Universita degli Studi

Padua, , Italy

Site Status

Fodazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Site Status

Azienda Ospedaliera S. Camillo-Forlanini

Roma, , Italy

Site Status

Az. Ospedaliero-Universitaria S. Giovanni Battista di Torino

Torino, , Italy

Site Status

Auckland Hospital

Auckland, , New Zealand

Site Status

Rikshospitalet, Hjertemedisinskavdeling

Oslo, , Norway

Site Status

Cardiovascular Center of Puerto Rico and the Caribbean

San Juan, , Puerto Rico

Site Status

Hospital Universitario Reina Sofia

Córdoba, , Spain

Site Status

Hospital Puerta de Hierro Majadahonda

Madrid, , Spain

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Papworth Hospital

Cambridge, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Canada France Germany Italy New Zealand Norway Puerto Rico Spain Taiwan United Kingdom

Other Identifiers

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CRAD001A2310

Identifier Type: -

Identifier Source: org_study_id