Cardiovascular Safety of Xenon in General Anaesthesia, in Patient With Cardiovascular Risk in Non Cardiac Surgery (CARVASAXe)

Cardiovascular Safety of Xenon in General Anaesthesia, in Patient With Cardiovascular Risk in Non Cardiac Surgery: A Phase III Multicenter Randomized Controlled Study

The Primary Objective is to show non inferiority in cardiac safety (i.e myocardial necrosis-MN- assessed by positive cardiac Troponin I -cTnI- ultrasensitive assay) of a Xenon based general anesthesia procedure in patients with elevated cardiac risk scheduled for atherosclerotic vascular surgery (i.e patient with Coronary Arteries Disease risk) when compared to sevoflurane based general anesthesia procedure, postoperatively up to 3 days.

Study Overview

• Status: Completed
• Conditions: Elevated Cardiac Risk; Coronary Arteries Disease Risk
• Intervention / Treatment: Drug: Sevoflurane; Drug: Xenon

Detailed Description

The Primary endpoint is defined as an increase above the 99th percentile of highly sensitive cardiac Troponin I (cTnI) at any time during the 72 h post operatively. Time frame 3 days post-op;

Key secondary endpoint(s) are routine (Local laboratory) dosage of standard cardiac Troponin I (cTnI) at D1 (24h) and D3 (72 h) post operatively, and also in case of any suspicion of Myocardial Infarction , Routine cardiac safety monitoring.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Hôpital Saint Joseph
  • Paris, France, 75013
    • CHU Pitié Salpétrière
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67091
      • Nouvel Hôpital Civil
  • Bouches du Rhône
    • Marseille, Bouches du Rhône, France, 13915
      • CHU Nord
  • Calvados
    • Caen, Calvados, France, 14033 Cedex 9
      • Centre Hospitalier Universitaire de Caen - Pôle Anesthésie-Réanimation-SAMU, Avenue de la Côte de Nacre
  • Côte d'Or
    • Dijon, Côte d'Or, France, 21079
      • CHU Dijon
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • Hopital Pellegrin
    • Bordeaux, Gironde, France, 33604
      • CHU Bordeaux Haut Lévèque
  • Ille et Vilaine
    • Rennes, Ille et Vilaine, France, 35009
      • CHU Rennes
  • Nord
    • Lille, Nord, France, 59037 Cedex
      • CHRU, Hôpital Cardiologique, Département Anesthésie-Réanimation, Bld du Président Jules Leclerc
  • Puy de Dôme
    • Clermont Ferrand, Puy de Dôme, France, 63003
      • CHU Clermont Ferrand
  • Val de Marne
    • Creteil, Val de Marne, France, 94000
      • Hopital Henri Mondor
  • Vienne
    • Poitiers, Vienne, France, 86021 Cedex
      • CHU Poitiers, Service Anesthésie-Réanimation, 2 rue de Milétrie, BP577

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:

• Age ≥ 18 years
• Scheduled for atherosclerotic vascular elective surgery with presumed fast-track,

• Cardiac ischaemic risk supported by:

  • History of myocardial infarction older than 1 month and/or
  • Documented Stable angina (asymptomatic ± medical treatment) and/or
  • History of coronary revascularisation, and/or
  • Surgical Risk Index ("Lee" index) ≥ 3.
  • Written informed consent

Exclusion Criteria:

• Unstable angina within the last 30 days,
• Non controlled arterial Hypertension .
• Severe Cardiac heart Failure (NYHA IV)
• Severe Chronic Obstructive Pulmonary Disease
• Patient already randomized in another ongoing clinical trial
• Patient with recent myocardial infarction (M.I) (less than one month )
• Patient already included in a clinical trial
• History of hypersensitivity to study drugs( i.e Xenon, propofol, sevoflurane, desflurane, isoflurane)
• Malignant hyperthermia
• Documented Elevated intracranial pressure
• Preeclampsia or eclampsia
• Pregnancy and lactation
• Presumed uncooperativeness or legal incapacity

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xenon; 0.8-1.1 minimum alveolar concentration (MAC) Xenon in 30 % oxygen (Group A)	Drug: Xenon; Other Names: LENOXe
Active Comparator: sevoflurane; 0.8-1.1 Minimum Alveolar Concentration (MAC) Sevoflurane in 30 % oxygen (Group B)	Drug: Sevoflurane; Other Names: Sevo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Myocardial Necrosis (MN)	Myocardial Necrosis: at least 1 value of serum cardiac troponin I above the 99th percentile (measurement performed by a central laboratory using the ABBOTT-ARCHITECT technique)	3 Postoperative Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Cardiac Troponin I or T Above the 99th Percentile (Local Laboratories)	At least 1 value of serum cardiac troponin I or T above the 99th percentile (measurements performed by local laboratories using different techniques)	3 Postoperative days
Number of Participants With Myocardial Infarction (MI)	Patients with Confirmed Myocardial Infarction (MI) by the Investigators	3 Postoperative Days
Number of Participants With Cerebro-Vascular Event	Patients with Cerebro-Vascular Event in the FAS	3 postoperative days
Number of Participants With Life-Threatening Arrhythmia	Patients with Life-Threatening Arrhythmia in the FAS	3 Postoperative Days
Number of Participants Who Died From Cardiac Origin	No patient died from a cardiac cause during the 3 postoperative days.	3 postoperative days
Number of Participants With Composite Endpoint	Patients with at least 1 event among MN assessed by central laboratory, MI, Cerebro-Vascular event, Life-Threatening Arrhythmia and Death from Cardiac Origin	3 postoperative days
Systolic Blood Pressure (SBP)	Repeated Systolic Blood Pressure measurements during the perioperative period	From pre-induction to recovery of anesthesia
Vital Signs (SBP and DBP Changes)	Changes from baseline for Systolic and Diastolic Blood Pressure (SBP and DBP)	From pre-induction to Postoperative Day 3
Vital Signs (Heart Rate Changes)	Changes from baseline for Heart Rate (HR)	From pre-induction to Postoperative Day 3
Number of Participants With Chest Pain During the 3 Postoperative Days	Patients with Chest Pain reported at least once per day during the 3 Postoperative Days	From Day 0 until Postoperative Day 3
Urine Output	Urine volume in milliliter (mL) during the first postoperative hours	From Day 0 until Postoperative Day 1

Collaborators and Investigators

• Sponsor: Air Liquide Santé International
• Collaborators: Eurofins Biomnis; MONITORING FORCE GROUP CROs; Inferential
• Investigators: Principal Investigator: Yanncik Le Manach, MD, CHU PITIE SALPETRIERE, PARIS, FRANCE; Study Chair: Pierre CORIAT, MD Prof, CHU PITIE SALPETRIERE, PARIS, FRANCE; Study Chair: Benoit VALLET, MD Prof, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 4, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimate): May 11, 2010

Study Record Updates

• Last Update Posted (Estimate): June 17, 2014
• Last Update Submitted That Met QC Criteria: May 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Cardiovascular risk; Xenon; Cardiac safety; Non cardiac surgery; Atherosclerotic vascular surgery
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Sevoflurane
• Other Study ID Numbers: EudraCT #2010-018703-28