The ENIGMA II Trial:Nitrous Oxide Anaesthesia and Cardiac Morbidity After Major Surgery: a Randomised Controlled Trial

Phase 4

Completed

• Conditions: Coronary Artery Disease
• Interventions: Other: No Nitrous Oxide; Other: Nitrous Oxide

• Registration Number: NCT00430989
• Lead Sponsor: Bayside Health

Brief Summary

To investigate the safety of nitrous oxide (N2O) anaesthesia in patients with risk factors for coronary artery disease undergoing major surgery.

Detailed Description

Approximately 25% of patients undergoing major surgery have known coronary artery disease (CAD) or risk factors for CAD.

N2O interferes with vitamin B12 and folate metabolism. This impairs production of methionine (from homocysteine), used to form tetrahydrofolate and thymidine during DNA synthesis. It has been repeatedly demonstrated that N2O anaesthesia increases postoperative homocysteine levels. Chronic hyperhomocysteinaemia is associated with cardiovascular disease, and acute hyperhomocysteinaemia is known to cause endothelial dysfunction. One small trial has demonstrated an increased incidence of postoperative myocardial ischaemia in patients receiving N2O anaesthesia. Reducing postoperative myocardial infarction and death are important aims for those with CAD undergoing major surgery.

Our previous trial (ENIGMA) studied 2050 patients and identified some serious adverse effects, but most patients were not at risk of CAD and so we could not reliably assess serious cardiac complications. We propose a large simple randomized clinical trial of 7,000 patients to provide a definitive evaluation of the safety of N2O anaesthesia.

Updated statistical analysis plan can be found at www.enigma2.org.au.

Study Timeline

• Study First Submitted: 2007-01-31
• Study First Submitted QC: 2007-02-01
• Study First Posted: 2007-02-02
• Study Start: 2007-04
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Results First Submitted: 2016-02-16
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-18
• Results First Posted: 2019-06-17
• Last Update Submitted: 2019-11-24
• Last Update Posted: 2019-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7112

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
No Nitrous Oxide	No Nitrous Oxide	General anaesthesia not containing Nitrous oxide with fraction of inspired oxygen at 30%
70% Nitrous Oxide	Nitrous Oxide	General anaesthesia using 70% Nitrous Oxide with fraction of inspired oxygen at 30%

Primary Outcome Measures

Name	Time	Method
The Primary Endpoint is a Composite of Death and Cardiovascular Events (Clinical and Silent MI, Cardiac Failure, Cardiac Arrest, Pulmonary Embolism, and Stroke) Measured at 30 Days After Surgery.	30 days post op

Secondary Outcome Measures

Name	Time	Method
Myocardial Infarction (MI)	30 days post op
Pulmonary Embolism	30 Days Post op
Cardiac Arrest	30 days
Stroke	30 Days Post op
Wound Infection	30 Days Post op
Hospital Stay (Days)	30 Days Post Op

Trial Locations

Locations (1)

Alfred Hosptial; 🇦🇺 Melbourne, Victoria, Australia