Title

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

    Phase 3
  • Study Type

    Interventional
  • Study Participants

    600
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.
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 Started
May 31
2010
Primary Completion
Jul 31
2012
Study Completion
Jul 31
2012
Results Posted
Jun 17
2014
Estimate
Last Update
Jun 17
2014
Estimate

Drug Xenon

  • Other names: LENOXe

Drug Sevoflurane

  • Other names: Sevo

Xenon Experimental

0.8-1.1 minimum alveolar concentration (MAC) Xenon in 30 % oxygen (Group A)

sevoflurane Active Comparator

0.8-1.1 Minimum Alveolar Concentration (MAC) Sevoflurane in 30 % oxygen (Group B)

Criteria

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

Summary

Xenon

Sevoflurane

All Events

Event Type Organ System Event Term Xenon Sevoflurane

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)

Xenon

57.0
participants

Sevoflurane

54.0
participants

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)

Xenon

27.0
participants

Sevoflurane

25.0
participants

Number of Participants With Myocardial Infarction (MI)

Patients with Confirmed Myocardial Infarction (MI) by the Investigators

Xenon

5.0
participants

Sevoflurane

3.0
participants

Number of Participants With Cerebro-Vascular Event

Patients with Cerebro-Vascular Event in the FAS

Xenon

2.0
participants

Sevoflurane

3.0
participants

Number of Participants With Life-Threatening Arrhythmia

Patients with Life-Threatening Arrhythmia in the FAS

Xenon

2.0
participants

Sevoflurane

Number of Participants Who Died From Cardiac Origin

No patient died from a cardiac cause during the 3 postoperative days.

Xenon

Sevoflurane

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

Sevoflurane

56.0
participants

Xenon

61.0
participants

Systolic Blood Pressure (SBP)

Repeated Systolic Blood Pressure measurements during the perioperative period

Xenon

Baseline

146.1
mm Hg (Mean)
Standard Deviation: 21.6

Maximum SBP-Awakening Time

156.6
mm Hg (Mean)
Standard Deviation: 29.1

Maximum SBP-Induction Time

156.0
mm Hg (Mean)
Standard Deviation: 26.9

Maximum SBP- Maintenance Time

157.8
mm Hg (Mean)
Standard Deviation: 28.0

Minimum SBP- Awakening Time

123.8
mm Hg (Mean)
Standard Deviation: 25.1

Minimum SBP-Induction Time

90.6
mm Hg (Mean)
Standard Deviation: 21.3

Minimum SBP-Maintenance Time

94.8
mm Hg (Mean)
Standard Deviation: 17.8

Sevoflurane

Baseline

147.3
mm Hg (Mean)
Standard Deviation: 23.6

Maximum SBP-Awakening Time

153.4
mm Hg (Mean)
Standard Deviation: 27.6

Maximum SBP-Induction Time

153.6
mm Hg (Mean)
Standard Deviation: 29.6

Maximum SBP- Maintenance Time

144.6
mm Hg (Mean)
Standard Deviation: 26.1

Minimum SBP- Awakening Time

117.6
mm Hg (Mean)
Standard Deviation: 23.0

Minimum SBP-Induction Time

90.3
mm Hg (Mean)
Standard Deviation: 20.7

Minimum SBP-Maintenance Time

83.8
mm Hg (Mean)
Standard Deviation: 14.2

Vital Signs (SBP and DBP Changes)

Changes from baseline for Systolic and Diastolic Blood Pressure (SBP and DBP)

Xenon

DBP-Day 1

-6.05
mm Hg (Mean)
Standard Deviation: 14.91

DBP- Day 2

-3.32
mm Hg (Mean)
Standard Deviation: 14.53

DBP-Day 3

-3.73
mm Hg (Mean)
Standard Deviation: 14.05

SBP-Day 1

-12.2
mm Hg (Mean)
Standard Deviation: 25.4

SBP-Day 2

-10.8
mm Hg (Mean)
Standard Deviation: 26.6

SBP-Day 3

-11.9
mm Hg (Mean)
Standard Deviation: 24.7

Sevoflurane

DBP-Day 1

-6.15
mm Hg (Mean)
Standard Deviation: 15.10

DBP- Day 2

-1.46
mm Hg (Mean)
Standard Deviation: 13.41

DBP-Day 3

-2.61
mm Hg (Mean)
Standard Deviation: 13.90

SBP-Day 1

-14.2
mm Hg (Mean)
Standard Deviation: 26.8

SBP-Day 2

-10.7
mm Hg (Mean)
Standard Deviation: 25.6

SBP-Day 3

-12.2
mm Hg (Mean)
Standard Deviation: 25.0

Vital Signs (Heart Rate Changes)

Changes from baseline for Heart Rate (HR)

Xenon

HR-Day 1

6.35
beats per minute (Mean)
Standard Deviation: 12.03

HR-Day 2

8.81
beats per minute (Mean)
Standard Deviation: 13.64

HR-Day 3

6.44
beats per minute (Mean)
Standard Deviation: 11.72

Sevoflurane

HR-Day 1

6.35
beats per minute (Mean)
Standard Deviation: 12.91

HR-Day 2

9.85
beats per minute (Mean)
Standard Deviation: 12.93

HR-Day 3

8.9
beats per minute (Mean)
Standard Deviation: 14.14

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

Xenon

Day 0

Day 1

Day 2

1.0
participants

Day 3

2.0
participants

Sevoflurane

Day 0

Day 1

2.0
participants

Day 2

2.0
participants

Day 3

3.0
participants

Urine Output

Urine volume in milliliter (mL) during the first postoperative hours

Xenon

1279.0
mL (Mean)
Standard Deviation: 723.1

Sevoflurane

1324.4
mL (Mean)
Standard Deviation: 631.8

Total

590
Participants

Age, Continuous

70.9
years (Mean)
Standard Deviation: 10.2

Participants with Baseline Cardiac Troponin (Central Laboratory)

Region of Enrollment

Sex: Female, Male

Overall Study

Xenon

Sevoflurane