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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Coronary Artery Bypass Graft Surgery; General Anesthetic Drug Allergy
• Intervention / Treatment: Drug: Xenon; Drug: Sevoflurane; Drug: Propofol

• Study Type: Interventional
• Enrollment (Actual): 509
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hopital Cardiovasculaire et Pneumologique Louis Pradel
  • Caen, France, 14033
    • CHU de Caen
  • Nantes, France, 44093
    • Hôpital G&R Laennec - Centre Hospitalier Universitaire de Nantes
  • Paris, France, 75013
    • Centre Hospitalo-Universitaire Pitié-Salpetrière
  • Pessac, France, 33600
    • Hopital Du Haut-Leveque
  • Rennes, France, 35033
    • Hopital Pontchaillou
  • Strasbourg, France, 67091
    • Hôpitaux Universitaires de Strasbourg - Nouvel Hôpital Civil
  • Toulouse, France, 31059
    • Centre Hospitalier de Rangueil
• Germany
  • Aachen, Germany, 52074
    • University Hospital Aachen
  • Bremen, Germany, 28277
    • Klinikum Links der Weser - Senator-Wessling-Str. 1
  • Frankfurt, Germany, 60590
    • University Hospital Frankfurt am Main
  • Lubeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein
  • Rostock, Germany, 18057
    • University Hospital Rostock
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitätsklinikum Schleswig-Holstein
• Italy
  • Rome, Italy, 00161
    • Policlinico Umberto I
• Netherlands
  • Amsterdam, Netherlands, 1100 DD
    • Academic Medical Center - University of Amsterdam
  • Rotterdam, Netherlands, 3000 CA
    • Thorax Center - Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Air Liquide Santé International
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Jan HOFLAND, MD, PhD, Thorax Centre Erasmus MC, Rotterdam, the Netherlands

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 10, 2011
• First Posted (Estimate): February 11, 2011

Study Record Updates

• Last Update Posted (Estimate): December 21, 2015
• Last Update Submitted That Met QC Criteria: December 18, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Coronary artery disease; Propofol; Xenon; Coronary artery bypass graft; Anaesthesia; Sevoflurane; Total intravenous anaesthesia
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Drug Hypersensitivity; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Sevoflurane
• Other Study ID Numbers: ALMED-09-C3-026