Custodiol-N Versus Custodiol®: Results from A Prospective Noninferiority Randomised Single Blind, Multicenter Phase 3 Trial In Patients Undergoing Heart Transplantation.

Abstract

BACKGROUND Custodiol® is a well-established preservation solution for organ transplantation and was the basis for the development of Custodiol-N to improve graft preservation. Previous results in coronary artery bypass graft surgery have shown effective cardiac protection without safety concerns. This study aimed to evaluate the safety and ability of Custodiol-N to preserve cardiac grafts for heart transplantation. METHODS This prospective, randomized, single-blind, multicenter, non-inferiority study was conducted at three centers in Austria and Germany. The primary endpoint was creatine kinase (CK-MB) peak value from 4-168 hours after opening of the aortic cross-clamp, with a 30% non-inferiority margin. Key secondary efficacy endpoints include patient and graft survival, incidence of primary graft failure, or length of stay in the intensive care unit. The primary and secondary endpoints were analyzed in both the treated and per protocol populations. RESULTS A total of 105 randomized patients received Custodiol® (n=52) or Custodiol-N (n=53) preserved hearts. Average donor age and ischemic times were comparable. Average CK-MB peak values were 176.94±189.61 U/L for the Custodiol® vs. 130.51±69.60 U/L for the Custodiol-N group (p-value for non-inferiority of Custodiol-N by 30% <.0001). Patient survival was comparable 1-year post-transplantation (90.4% for Custodiol® vs 88.7% for Custodiol-N). The incidence of primary graft failure and median length of intensive care unit stay were higher for Custodiol® group. Safety assessment showed evenly distributed adverse events. CONCLUSIONS This study shows that Custodiol-N is safe, non-inferior, and provides similar cardiac graft protection as the established Custodiol® solution.