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

Novartis

Status and phase: Completed; Phase 3

Conditions: Graft Rejection

Treatments: Drug: cyclosporine; Drug: everolimus; Drug: mycophenolate mofetil; Drug: corticosteroids

Study type: Interventional

Funder types: Industry

Identifiers

NCT00300274

CRAD001A2310

Details and patient eligibility

About

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.

Enrollment: 721 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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721 participants in 3 patient groups

everolimus 1.5 mg

Experimental group

Description:

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.

Treatment:

Drug: everolimus

Drug: corticosteroids

Drug: cyclosporine

everolimus 3.0 mg

Experimental group

Description:

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.

Treatment:

Drug: everolimus

Drug: corticosteroids

Drug: cyclosporine

mycophenolate mofetil

Active Comparator group

Description:

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:

Drug: mycophenolate mofetil

Drug: corticosteroids

Drug: cyclosporine