Trial Outcomes & Findings for Cardiovascular Safety of Xenon in General Anaesthesia, in Patient With Cardiovascular Risk in Non Cardiac Surgery (NCT NCT01120405)

NCT ID: NCT01120405

Last Updated: 2014-06-17

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

600 participants

Primary outcome timeframe

3 Postoperative Days

Results posted on

2014-06-17

Participant Flow

Participant milestones

Participant milestones
Measure	Xenon 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Overall Study STARTED	298	302
Overall Study COMPLETED	271	269
Overall Study NOT COMPLETED	27	33

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xenon n=295 Participants 0.8-1.1 Minimal Alveolar Concentration in 30% oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimal Alveolar Concentration in 30% oxygen (Group B)	Total n=590 Participants Total of all reporting groups
Age, Continuous	70.6 years STANDARD_DEVIATION 10.3 • n=5 Participants	71.2 years STANDARD_DEVIATION 10.2 • n=7 Participants	70.9 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	52 Participants n=7 Participants	109 Participants n=5 Participants
Sex: Female, Male Male	238 Participants n=5 Participants	243 Participants n=7 Participants	481 Participants n=5 Participants
Region of Enrollment France	295 participants n=5 Participants	295 participants n=7 Participants	590 participants n=5 Participants
Participants with Baseline Cardiac Troponin (Central Laboratory) > 99th percentile	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants
Participants with Baseline Cardiac Troponin (Central Laboratory) ≤ 99th percentile	269 participants n=5 Participants	269 participants n=7 Participants	538 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 Postoperative Days

Population: Per protocol set (PPS): Randomised patients who started general anaesthesia induction and with no major protocol violations. Patients were assigned to the treatment groups as randomised, i.e. the treatment groups were based on the treatment allocated by randomisation.

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)

Outcome measures

Outcome measures
Measure	Xenon n=273 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=261 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Myocardial Necrosis (MN)	57 participants	54 participants

SECONDARY outcome

Timeframe: 3 Postoperative days

Population: Full analysis set (FAS): Randomised patients who started general anaesthesia induction. Patients were assigned to the treatment groups as randomised, i.e. the treatment groups were based on the treatment allocated by randomisation.

At least 1 value of serum cardiac troponin I or T above the 99th percentile (measurements performed by local laboratories using different techniques)

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Cardiac Troponin I or T Above the 99th Percentile (Local Laboratories)	27 participants Interval 20.0 to 34.0	25 participants Interval 20.0 to 30.0

SECONDARY outcome

Timeframe: 3 Postoperative Days

Patients with Confirmed Myocardial Infarction (MI) by the Investigators

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Myocardial Infarction (MI)	5 participants Interval 10.0 to 28.0	3 participants Interval 10.0 to 22.0

SECONDARY outcome

Timeframe: 3 postoperative days

Patients with Cerebro-Vascular Event in the FAS

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Cerebro-Vascular Event	2 participants	3 participants

SECONDARY outcome

Timeframe: 3 Postoperative Days

Patients with Life-Threatening Arrhythmia in the FAS

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Life-Threatening Arrhythmia	2 participants	0 participants

SECONDARY outcome

Timeframe: 3 postoperative days

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

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants Who Died From Cardiac Origin	0 participants	0 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Composite Endpoint	61 participants Interval 60.0 to 62.0	56 participants Interval 50.0 to 62.0

SECONDARY outcome

Timeframe: From pre-induction to recovery of anesthesia

Repeated Systolic Blood Pressure measurements during the perioperative period

Outcome measures

Outcome measures
Measure	Xenon n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=295 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Systolic Blood Pressure (SBP) Baseline	146.1 mm Hg Standard Deviation 21.6	147.3 mm Hg Standard Deviation 23.6
Systolic Blood Pressure (SBP) Minimum SBP-Induction Time	90.6 mm Hg Standard Deviation 21.3	90.3 mm Hg Standard Deviation 20.7
Systolic Blood Pressure (SBP) Minimum SBP-Maintenance Time	94.8 mm Hg Standard Deviation 17.8	83.8 mm Hg Standard Deviation 14.2
Systolic Blood Pressure (SBP) Minimum SBP- Awakening Time	123.8 mm Hg Standard Deviation 25.1	117.6 mm Hg Standard Deviation 23.0
Systolic Blood Pressure (SBP) Maximum SBP-Induction Time	156.0 mm Hg Standard Deviation 26.9	153.6 mm Hg Standard Deviation 29.6
Systolic Blood Pressure (SBP) Maximum SBP- Maintenance Time	157.8 mm Hg Standard Deviation 28.0	144.6 mm Hg Standard Deviation 26.1
Systolic Blood Pressure (SBP) Maximum SBP-Awakening Time	156.6 mm Hg Standard Deviation 29.1	153.4 mm Hg Standard Deviation 27.6

SECONDARY outcome

Timeframe: From pre-induction to Postoperative Day 3

Population: Treated set (TS): Randomised patients who received the study medication. Patients were assigned to the treatment groups as treated, i.e. the treatment groups were based on the treatment actually received.

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

Outcome measures

Outcome measures
Measure	Xenon n=292 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=294 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Vital Signs (SBP and DBP Changes) SBP-Day 1	-12.2 mm Hg Standard Deviation 25.4	-14.2 mm Hg Standard Deviation 26.8
Vital Signs (SBP and DBP Changes) SBP-Day 2	-10.8 mm Hg Standard Deviation 26.6	-10.7 mm Hg Standard Deviation 25.6
Vital Signs (SBP and DBP Changes) SBP-Day 3	-11.9 mm Hg Standard Deviation 24.7	-12.2 mm Hg Standard Deviation 25.0
Vital Signs (SBP and DBP Changes) DBP-Day 1	-6.05 mm Hg Standard Deviation 14.91	-6.15 mm Hg Standard Deviation 15.10
Vital Signs (SBP and DBP Changes) DBP- Day 2	-3.32 mm Hg Standard Deviation 14.53	-1.46 mm Hg Standard Deviation 13.41
Vital Signs (SBP and DBP Changes) DBP-Day 3	-3.73 mm Hg Standard Deviation 14.05	-2.61 mm Hg Standard Deviation 13.90

SECONDARY outcome

Timeframe: From pre-induction to Postoperative Day 3

Changes from baseline for Heart Rate (HR)

Outcome measures

Outcome measures
Measure	Xenon n=292 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=294 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Vital Signs (Heart Rate Changes) HR-Day 3	6.44 beats per minute Standard Deviation 11.72	8.90 beats per minute Standard Deviation 14.14
Vital Signs (Heart Rate Changes) HR-Day 1	6.35 beats per minute Standard Deviation 12.03	6.35 beats per minute Standard Deviation 12.91
Vital Signs (Heart Rate Changes) HR-Day 2	8.81 beats per minute Standard Deviation 13.64	9.85 beats per minute Standard Deviation 12.93

SECONDARY outcome

Timeframe: From Day 0 until Postoperative Day 3

Patients with Chest Pain reported at least once per day during the 3 Postoperative Days

Outcome measures

Outcome measures
Measure	Xenon n=292 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=294 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Number of Participants With Chest Pain During the 3 Postoperative Days Day 0	0 participants	0 participants
Number of Participants With Chest Pain During the 3 Postoperative Days Day 1	0 participants	2 participants
Number of Participants With Chest Pain During the 3 Postoperative Days Day 2	1 participants	2 participants
Number of Participants With Chest Pain During the 3 Postoperative Days Day 3	2 participants	3 participants

SECONDARY outcome

Timeframe: From Day 0 until Postoperative Day 1

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

Outcome measures

Outcome measures
Measure	Xenon n=292 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=294 Participants 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Urine Output	1279.0 mL Standard Deviation 723.1	1324.4 mL Standard Deviation 631.8

Adverse Events

Xenon

Serious events: 17 serious events

Other events: 79 other events

Deaths: 0 deaths

Sevoflurane

Serious events: 17 serious events

Other events: 84 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Xenon n=292 participants at risk 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=294 participants at risk 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Injury, poisoning and procedural complications Procedural Pain	7.2% 21/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	7.8% 23/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Procedural Hypertension	8.2% 24/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	4.8% 14/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Procedural Nausea	7.2% 21/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	4.1% 12/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Procedural Vomiting	5.5% 16/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	3.4% 10/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
General disorders Hyperthermia	4.5% 13/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	5.8% 17/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
General disorders Pain	2.7% 8/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	5.1% 15/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Vascular disorders Hypertension	5.8% 17/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	6.8% 20/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.

Additional Information

Yannick LE MANACH, MD, PhD

Population Health Research Institute - Mc Master University, Hamilton CANADA

Phone: 0012892606840

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Air Liquide Sante International may delay publication or disclosure for a term not exceeding eighteen (18) months with effect from the request in the event that Air Liquide Sante International wishes to seek protection of the results of the Trial by industrial property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Xenon n=292 participants at risk 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group A)	Sevoflurane n=294 participants at risk 0.8-1.1 Minimum Alveolar Concentration in 30 % oxygen (Group B)
Hepatobiliary disorders Gallblader Necrosis	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Myocardial Infarction	1.0% 3/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	1.0% 3/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.68% 2/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Acute Coronary Syndrome	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Acute Myocardial Infarction	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Atrial Fibrillation	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Bradyarrhythmia	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Cardiac disorders Subendocardial ischemia	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.68% 2/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	1.0% 3/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Post Procedural Haematoma	0.68% 2/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.68% 2/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Procedural Hypotension	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Graft thrombosis	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Operative Haemorrhage	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Shunt Trombosis	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Injury, poisoning and procedural complications Wound	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Nervous system disorders Ischaemic Stroke	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.68% 2/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Nervous system disorders Agitation	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Nervous system disorders Cerebrovascular Accident	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Nervous system disorders Confusional State	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Nervous system disorders Loss of Consciousness	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Nervous system disorders Transient Ischaemic Attack	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Vascular disorders Peripheral Ischaemia	0.68% 2/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Vascular disorders Hypertension	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.34% 1/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Investigations Troponin Increased	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.68% 2/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	1.0% 3/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.
Psychiatric disorders Aggression	0.34% 1/292 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.	0.00% 0/294 • Adverse Events observed after the start of study drug administration and during postoperative 3-day period Participants at risks are the patients from the Treated Set, ie randomised patients who received the study medication.