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

Phase 3

Completed

• Conditions: Elevated Cardiac Risk; Coronary Arteries Disease Risk
• Interventions: Drug: Xenon; Drug: Sevoflurane

• Registration Number: NCT01120405
• Lead Sponsor: Air Liquide Santé International

Brief Summary

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.

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 Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-05-04
• Study First Submitted QC: 2010-05-07
• Study First Posted: 2010-05-11
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Results First Submitted: 2014-03-20
• Status Verified: 2014-05
• Results First Submitted QC: 2014-05-20
• Last Update Submitted: 2014-05-20
• Results First Posted: 2014-06-17
• Last Update Posted: 2014-06-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 600

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Xenon	Xenon	0.8-1.1 minimum alveolar concentration (MAC) Xenon in 30 % oxygen (Group A)
sevoflurane	Sevoflurane	0.8-1.1 Minimum Alveolar Concentration (MAC) Sevoflurane in 30 % oxygen (Group B)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Myocardial Necrosis (MN)	3 Postoperative Days	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)

Secondary Outcome Measures

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

Trial Locations

Locations (13)

Centre Hospitalier Universitaire de Caen - Pôle Anesthésie-Réanimation-SAMU, Avenue de la Côte de Nacre; 🇫🇷 Caen, Calvados, France

Nouvel Hopital Civil; 🇫🇷 Strasbourg, Bas Rhin, France

CHU Nord; 🇫🇷 Marseille, Bouches du Rhône, France

CHU Dijon; 🇫🇷 Dijon, Côte d'Or, France

Hopital Pellegrin; 🇫🇷 Bordeaux, Gironde, France

CHU Bordeaux Haut Lévèque; 🇫🇷 Bordeaux, Gironde, France

CHU Rennes; 🇫🇷 Rennes, Ille et Vilaine, France

CHRU, Hôpital Cardiologique, Département Anesthésie-Réanimation, Bld du Président Jules Leclerc; 🇫🇷 Lille, Nord, France

CHU Clermont Ferrand; 🇫🇷 Clermont Ferrand, Puy de Dôme, France

Hopital Henri Mondor; 🇫🇷 Creteil, Val de Marne, France

CHU Poitiers, Service Anesthésie-Réanimation, 2 rue de Milétrie, BP577; 🇫🇷 Poitiers, Vienne, France

Chu Pitie Salpetriere; 🇫🇷 Paris, France

Hopital Saint Joseph; 🇫🇷 Paris, France