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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00300274




Registration number
NCT00300274
Ethics application status
Date submitted
6/03/2006
Date registered
8/03/2006
Date last updated
16/08/2012

Titles & IDs
Public title
Efficacy and Safety of Everolimus in Recipients of Heart Transplants to Prevent Acute and Chronic Rejection
Scientific title
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
Secondary ID [1] 0 0
CRAD001A2310
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft Rejection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - everolimus
Treatment: Drugs - mycophenolate mofetil
Treatment: Drugs - cyclosporine
Treatment: Drugs - corticosteroids

Experimental: 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.

Experimental: 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.

Active comparator: 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.


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

Treatment: Drugs: mycophenolate mofetil
Mycophenolate mofetil supplied as 500 mg tablets.

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

Treatment: Drugs: corticosteroids
Corticosteroids standard dose.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Composite Efficacy Failure at 12 Months
Timepoint [1] 0 0
12 Months
Secondary outcome [1] 0 0
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 12 Months
Timepoint [1] 0 0
12 Months
Secondary outcome [2] 0 0
Renal Function Measured by Glomerular Filtration Rate (GFR) at 12 Months
Timepoint [2] 0 0
12 Months
Secondary outcome [3] 0 0
Change From Baseline in the Average Maximum Intimal Thickness at Month 12
Timepoint [3] 0 0
Baseline, Month 12
Secondary outcome [4] 0 0
Percentage of Participants With Cardiac Allograft Vasculopathy (CAV) at Month 12
Timepoint [4] 0 0
12 Months
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
12 Months
Secondary outcome [6] 0 0
Percentage of Participants With Composite Efficacy Failure at 24 Months
Timepoint [6] 0 0
24 Months
Secondary outcome [7] 0 0
Percentage of Participants With Graft Loss/Re-transplant, Death or Loss to Follow-up at 24 Months
Timepoint [7] 0 0
24 Months
Secondary outcome [8] 0 0
Renal Function Calculated by Glomerular Filtration Rate (GFR) at 24 Months
Timepoint [8] 0 0
24 Months
Secondary outcome [9] 0 0
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR of ISHLT Grade = 3A), Acute Rejection (AR) Associated With Hemodynamic Compromise (HDC), Graft Loss/Re-transplant and Death at Month 24
Timepoint [9] 0 0
24 Months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2011
Sample size
Target
Accrual to date
Final
721
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Chermside
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Argentina
State/province [16] 0 0
Santa Fe
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Austria
State/province [18] 0 0
Vienna
Country [19] 0 0
Belgium
State/province [19] 0 0
Bruxelles
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Nova Scotia
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
France
State/province [25] 0 0
Lyon
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Strasbourg
Country [28] 0 0
France
State/province [28] 0 0
Vandoeuvre les Nancy
Country [29] 0 0
Germany
State/province [29] 0 0
Bad Oeynhausen
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Hamburg
Country [32] 0 0
Germany
State/province [32] 0 0
Hannover
Country [33] 0 0
Germany
State/province [33] 0 0
Kiel
Country [34] 0 0
Germany
State/province [34] 0 0
Regensburg
Country [35] 0 0
Italy
State/province [35] 0 0
Bologna
Country [36] 0 0
Italy
State/province [36] 0 0
Cagliari
Country [37] 0 0
Italy
State/province [37] 0 0
Padova
Country [38] 0 0
Italy
State/province [38] 0 0
Pavio
Country [39] 0 0
Italy
State/province [39] 0 0
Roma
Country [40] 0 0
Italy
State/province [40] 0 0
Torino
Country [41] 0 0
New Zealand
State/province [41] 0 0
Auckland
Country [42] 0 0
Norway
State/province [42] 0 0
Oslo
Country [43] 0 0
Puerto Rico
State/province [43] 0 0
San Juan
Country [44] 0 0
Spain
State/province [44] 0 0
Cordoba
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Birmingham
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Cambridge
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis
Address 0 0
Novartis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00300274