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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Elevated Cardiac Risk, Coronary Arteries Disease Risk

Intervention / Treatment
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* Drug: Xenon
* Drug: Sevoflurane


Participation Criteria
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Eligibility Criteria
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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

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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xenon, Cardiac safety, Cardiovascular risk, Non cardiac surgery, Atherosclerotic vascular surgery