Phase III Study Comparing Two Methods of Cardioplegia in Coronary Artery Bypass Surgery

Study Overview
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Brief Summary
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Comparison of the cardioprotective effects and safety of two cardioplegic solutions (solutions used during a cardiac arrest in the heart surgery) in patients undergoing cardiopulmonary bypass for coronary artery bypass surgery.

Detailed Description
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The objective of this investigation is to compare the cardioprotective effects and safety of two cardioplegic solutions, HTK Cardioplegic Solution (Custodiol) and Custodiol-N in patients undergoing cardiopulmonary bypass for coronary artery bypass surgery. The study design is a prospective, double blind, multicenter, randomized, Phase III comparison study intended to demonstrate non-inferiority in surgical outcome between Custodiol and Custodiol-N as determined by CK-MB area under the curve (primary endpoint), catecholamine requirement(cumulative dose) and cardiac Troponin T, occurrence of comorbid events postoperatively (e.g., myocardial infarction).

Official Title
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A Prospective Randomized Double Blind Multicenter Phase III Study Comparing Two Methods of Cardioplegia in Coronary Artery Bypass Surgery Custodiol-N Versus Custodiol

Conditions
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Coronary Artery Disease (CAD)

Intervention / Treatment
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* Drug: Custodiol-N
* Drug: Custodiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study population will be selected from patients of either sex with coronary artery disease (CAD) who are to undergo cardiopulmonary bypass for coronary artery bypass surgery. Patients >/=35 and </=80 years of age Male or female with 2 or 3 vessel coronary disease, who are scheduled for elective CBP surgery for coronary revascularisation Presence of definite CAD for which surgical intervention is deemed necessary, without evidence of ongoing infarction. Patients with unstable angina can be included as long as there is no objective (negative cardiac isoenzymes in the immediate six hours preceding CABG, current intravenous use of nitrate therapy) or subjective (absence of prolonged symptoms suggestive of coronary insufficiency that do not respond to pharmacologic intervention) evidence of myocardial necrosis. Eligibility for Swan-Ganz-Catheter Able to understand character and individual consequences of the clinical trial and to provide written informed consent to participate in the study No evidence of severe organic or psychiatric disease by history or physical examination No history of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or no any history of drug abuse or addiction within 12 months of study enrollment. Exclusion Criteria: Patients undergoing valve repair or replacement History of recent (< 6 weeks) Q-wave myocardial infarction Left ventricular ejection fraction < 35% (as assessed by any one of the following: contrast ventriculography, multigated acquisition scanning [MUGA], or 2-D ECHO) Patients on intra-aortic balloon devices or with history of previous coronary artery bypass surgery Pregnant or lactating patients Patients who have participated in any other investigational studies within 30 days previous to enrollment Patients in cardiogenic shock (defined as a systolic BP < 90 mmHg for over one hour despite inotropic and chronotropic support) Patients with severe chronic obstructive lung disease (FEV1 < 50%) Previous cardiac valvular disease (clinical relevant) Dialysis or creatinine > 2 mmol/L BMS-Stent < 4 weeks DES-Stent < 6 month Guidance depended Plavix therapy

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Custodiol<br>After cross clamping of the aorta on cardiopulmonary bypass, the Custodiol solution, at a temperature of 4 - 6°C, will be infused antegrade into the root of the aorta. | Drug: Custodiol<br>* Route of administration: by infusion duration: infusion technique will be continued for seven minutes dosage: until 1500-2000 mL of solution have been infused<br>|
| Experimental: Custodiol-N<br>After cross clamping of the aorta on cardiopulmonary bypass, the Custodiol-N solution, at a temperature of 4 - 6°C, will be infused antegrade into the root of the aorta. | Drug: Custodiol-N<br>* Route of administration: by infusion Dosage: will be infused antegrade into the root of the aorta until 1500-2000 mL of solution have been infused Duration: infusion technique will be continued for seven minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CK-MB area under the curve within 24 hours | Measurements will be carried out at the following timepoints: 4,8,12,16,20,24 hours (± 30 min) after release of the aortic cross clamp | Up to 24 hours after the aortic clamp release | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Catecholamine requirement | Catecholamine requirement on surgical ICU within 24 hours | 24 hours (cumulative dose) | 
| CK-MB peak | CK-MB peak on the days 2, 3, 4 and 5 after removal of aortic cross clamp | Up to day 5 | 
| Mortality any time during post-op through Day 30 | Mortality will be documented at any time during post-op through Day 30 | Up to Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAD, ACVB