Custodiol-N versus Custodiol: a prospective randomized double-blind multicentre phase III trial in patients undergoing elective coronary bypass surgery.

Gábor Szabó, Paige Brlecic, Sivakkanan Loganathan, Florian Wagner, Ardawan Rastan, Torsten Doenst, Matthias Karck, Gábor Veres

Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2022;62(5):ezac287

PMID: 35579350

Full Text on Ovid Technologies, Inc. View on PubMed

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.

Address: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.; Department of Cardiac Surgery, University of Halle, Halle (Saale), Germany.; Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.; Department of Cardiac Surgery, University of Hamburg, Hamburg, Germany.; Department of Cardiac and Vascular Surgery, Heart Center Rotenburg, Rotenburg, Germany.; Department of Cardiac Surgery, University of Jena, Jena, Germany.

DOI: 10.1093/ejcts/ezac287