A randomized, prospective, multi-center comparison of tacrolimus, mycophenolate mofetil (MMF) and steroids vs. cyclosporine (modified usp), mmf and steroids vs tacrolimus, sirolimus and steroids in de novo cardiac transplant recipients - 6 month report

Abstract

Acute cardiac rejection is one of the most common causes of mortality in the first year after cardiac transplantation. Several newer immunosuppressive agents are available and have shown efficacy however it has not been established which combinations of these agents are most beneficial to cardiac transplant patients. The primary objective of this prospective, randomized, open-label, multi-center trial in cardiac transplant recipients was to compare the incidence of rejection = ISHLT grade 3A or hemodynamic compromise, which requires treatment in the three triple-therapy immunosuppressive regimens used in the trial. The secondary objectives included comparison of patient and graft survival, incidence of normal lipid profile, safety (infectious complications, malignancies, adverse drug effects) and cumulative total dose of steroids and doses at 6 and 12 months in each treatment regimen. Methods: Between November 2001 and June 2003, 343 de novo cardiac transplant recipients from 28 U.S. sites were randomized 1:1:1 to one of three regimens: (1) tacrolimus, MMF and steroids (2) cyclosporine (modifed USP), MMF and steroids, and (3) tacrolimus, sirolimus and steroids. Additionally, anti-lymphocyte induction therapy (per institution protocol) for up to 5 days post transplant was allowed, and pravastatin or simvastatin were initiated in all patients unless contraindicated. All patients received CMV, PCP, fungal and bacterial prophylaxis. Timing of protocol endomyocardial biopsies were standardized and performed as clinically indicated. Primary efficacy and safety endpoints will be assessed at 6 months, with secondary efficacy and safety endpoints assessed at 6 and 12 months. Six month data on all patients will be analyzed and available for presentation at the 2004 ISHLT Meeting.