Custodiol-N versus Custodiol: a prospective randomized double-blind multicentre phase III trial in patients undergoing elective coronary bypass surgery. (17th May 2022)

• Record Type: Journal Article
• Authors: Szabó, Gábor; Brlecic, Paige; Loganathan, Sivakkanan; Wagner, Florian; Rastan, Ardawan; Doenst, Torsten; Karck, Matthias; Veres, Gábor
• Is Part Of: European journal of cardio-thoracic surgery. Volume 62:Number 5(2022)
• Publication Date: 2022-05-17
• Subjects: Custodiol -- Custodiol-N -- Organ protection; Heart -- Surgery -- Periodicals; Chest -- Surgery -- Periodicals; 617.54
• DOI: 10.1093/ejcts/ezac287
• Languages: English
• ISSNs: 1010-7940

Abstract

Abstract: OBJECTIVES: HTK-Solution (Custodiol) is a well-established cardioplegic and organ preservation solution. We currently developed a novel HTK-based solution, Custodiol-N, which includes iron chelators to reduce oxidative injury, as well as l -arginine, to improve endothelial function. In this first-in-human study, Custodiol-N was compared to Custodiol in patients undergoing elective coronary artery bypass surgery. The aim of this comparison was to evaluate the safety and ability of Custodiol-N to protect cardiac tissue. METHODS: The study was designed as a prospective randomized double-blind non-inferiority trial. Primary end point was area under the curve (AUC) of creatine kinase muscle-brain (CK-MB) within the first 24 h after surgery. Secondary end points included peak CK-MB and troponin-T and AUC of troponin-T release, cardiac index, cumulative catecholamine dose, intensive care unit stay and mortality. All values in the abstract are given as mean ± SD, P < 0.05 was considered statistically significant. RESULTS: Early termination of the trial was performed per protocol as the primary non-inferiority end-point was reached after inclusion of 101 patients. CK-MB AUC (878± 549 vs 779± 439 h U/l, non-inferiority P < 0.001, Custodiol vs Custodiol-N) and troponin-T AUC (12990± 8347 vs 13498± 6513 h pg/ml, noninferiority P < 0.001, Custodiol vs Custodiol-N) were similar in both groups. Although the trial was designed for non-inferiority, peak CK-MB (52± 40 vs 42± 28 U/l, superiority P < 0.03, Custodiol vs Custodiol-N) was significantly lower in the Custodiol-N group. CONCLUSIONS: This study shows that Custodiol-N is safe and provides similar cardiac protection as the established HTK-Custodiol solution. Significantly reduced peak CK-MB levels in the Custodiol-N group in the full analysis set may implicate a beneficial effect on ischaemia/reperfusion injury in the setting of coronary bypass surgery. Abstract : Although controversy exists as to the optimal cardioplegic solution despite numerous clinical and experimental studies [1, 2], one frequently used form is the crystalloid cardioplegic solution.