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Published on: September 20, 2019
Custodiol-N versus Custodiol: a prospective randomized double-blind multicentre phase III trial in patients
Gábor Szabó1,2, Paige Brlecic1, Sivakkanan Loganathan1,2
1Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
Insights
Custodiol-N, a novel cardioplegic solution, demonstrated safety and comparable cardiac protection to Custodiol in a first-in-human study. It showed a significant reduction in peak creatine kinase-MB, suggesting potential benefits for ischemia/reperfusion injury during coronary artery bypass surgery.
Area of Science:
- Cardiology
- Cardiothoracic Surgery
- Organ Preservation
Background:
- Custodiol (HTK-Solution) is a standard cardioplegic agent.
- Oxidative injury and endothelial dysfunction can impact cardiac outcomes post-surgery.
- Custodiol-N is a novel HTK-based solution incorporating iron chelators and L-arginine.
Purpose of the Study:
- To evaluate the safety and cardiac tissue protection of Custodiol-N compared to Custodiol.
- To assess Custodiol-N's efficacy in patients undergoing coronary artery bypass surgery (CABG).
Main Methods:
- Prospective, randomized, double-blind, non-inferiority trial.
- Primary endpoint: Area Under the Curve (AUC) of creatine kinase-muscle-brain (CK-MB) within 24 hours post-surgery.
- Secondary endpoints included troponin-T levels, cardiac index, and clinical outcomes.
Main Results:
- The trial was terminated early after 101 patients as the non-inferiority endpoint was met.
- CK-MB AUC and troponin-T AUC were similar between Custodiol and Custodiol-N groups.
- Peak CK-MB levels were significantly lower in the Custodiol-N group, indicating potential superiority.
Conclusions:
- Custodiol-N is safe and offers comparable cardiac protection to the established Custodiol solution.
- Reduced peak CK-MB levels suggest Custodiol-N may mitigate ischemia/reperfusion injury in CABG patients.
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.
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