Xenon Compared to Sevoflurane and Total Intravenous Anaesthesia for Coronary Artery Bypass Graft Surgery

Study Overview
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Brief Summary
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Xenon is a gaseous anaesthetic agent registered in several European countries. It has been administered safely during cardiac surgery in pilot studies. In animal studies, xenon decreases the size of experimental myocardial infarction. This 3-arm study will compare xenon, sevoflurane and a propofol-based total intravenous anaesthesia for maintenance of anaesthesia during coronary artery bypass graft surgery conducted with extra-corporeal circulation. Xenon and sevoflurane will be administered before and after extracorporeal circulation. Propofol will be administered during extracorporeal circulation in the three groups of patients. The study will compare the postoperative myocardial damage observed 24 hours after surgery from blood levels of troponin I, a largely accepted biomarker of myocardial necrosis. The main hypothesis is that the myocardial damage observed after xenon administration will not be superior to the damage observed after sevoflurane administration (non-inferiority). The second hypothesis is that the myocardial damage observed after xenon administration will be inferior to the damage observed after total intravenous anaesthesia.

Official Title
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Efficacy and Safety of Xenon Anaesthesia Compared to Sevoflurane Anaesthesia and Total Intravenous Anaesthesia for On-pump Coronary Artery Bypass Graft Surgery: a Randomised, Three-arm, Single-blind, International Study

Conditions
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Coronary Artery Disease, General Anesthetic Drug Allergy, Coronary Artery Bypass Graft Surgery

Intervention / Treatment
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* Drug: Xenon
* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: coronary artery disease elective surgery, planned coronary artery bypass graft moderate hypothermia or normothermia cardiac arrest cold and warm cardioplegia normal of moderately impaired left ventricular systolic function written informed consent Exclusion Criteria: pregnancy or child bearing potential ongoing treatment with nicorandil or sulfonylurea medication severe renal or hepatic dysfunction ongoing myocardial infarction or unstable angina

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xenon<br> | Drug: Xenon<br>* Inhaled xenon, maximal inspired concentration of 65%.<br>|
| Active Comparator: Sevoflurane<br> | Drug: Sevoflurane<br>* Inhaled sevoflurane, maximal inspired concentration of 1.8%.<br>|
| Active Comparator: Total intravenous anaesthesia<br> | Drug: Propofol<br>* Hourly dose of 2-4 mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Level of Troponin I | Blood level of troponin I measured by a central laboratory | Sampling performed 24 hours after the end of the surgical procedure | 
| Log-transformed Blood Level of Troponin I | Blood level of troponin I measured by a central laboratory | Sampling performed 24 hours after the end of the surgical procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depth of Anaesthesia | On-line monitoring of depth of anaesthesia from bi-spectral electroencephalogram analysis (BIS monitor) | 4 hours | 
| Arterial Oxygen Saturation | Arterial blood gases | 4 hours | 
| Haemodynamic Profile | Monitoring of heart rate, arterial blood pressure, central venous pressure. | 4 hours | 
| Presence or Absence of Postoperative Delirium | Confusion Assessment Method | 7 days | 
| Clinical Laboratory Tests |  | 7 days | 
| ECG Abnormalities |  | 7 days | 
| Vital Signs |  | 7 days | 
| Presence of Absence of Adverse Events, Including Myocardial Infarction |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xenon, Sevoflurane, Propofol, Total intravenous anaesthesia, Anaesthesia, Coronary artery disease, Coronary artery bypass graft