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Phase 4 N=7,112 Randomized Triple-blind Treatment

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

Coronary Artery Disease

Enrolled (actual)
7,112
Serious AEs
8.3%
Results posted
Jun 2019
Primary outcome: Primary: 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. — 283; 296 participants

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Nitrous Oxide (Other); No Nitrous Oxide (Other)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Bayside Health
Primary completion
Sep 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
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.
283; 296
SECONDARY
Myocardial Infarction (MI)
215; 219
SECONDARY
Cardiac Arrest
15; 19
SECONDARY
Pulmonary Embolism
18; 22
SECONDARY
Stroke
26; 19
SECONDARY
Wound Infection
321; 311
SECONDARY
Hospital Stay (Days)
6.1; 6.1

Summary

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

Eligibility Criteria

Inclusion Criteria

  • Adult males and females age ≥ 45 years, undergoing noncardiac surgery and general anaesthesia expected to exceed two hours.
  • At increased risk of cardiac events, defined as any of
  • history of coronary artery disease as defined by a history of any one of the following: i. angina ii. MI iii. segmental wall motion abnormality on echocardiography or a fixed defect on radionuclide imaging iv. a positive exercise stress test for cardiac ischaemia v. a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test for cardiac ischaemia vi. coronary revascularization (CABG or PTCA) vii. angiographic evidence of atherosclerotic stenosis > 50% of the diameter of any coronary artery viii. ECG with pathological Q waves in two contiguous leads
  • heart failure
  • cerebrovascular disease thought due to atherothrombotic disease
  • aortic or peripheral vascular disease
  • or three or more of the following risk factors:
  • age ≥70 years
  • any history of congestive heart failure
  • diabetes and currently on an oral hypoglycaemic agent or insulin therapy
  • current treatment for hypertension
  • preoperative serum creatinine >175 micro mol/L (> 2.0 mg/dl)
  • current or previous high cholesterol ≥6.2 mmol/L (> 240 mg/dl)
  • history of a transient ischemic attack (TIA) (i.e. a transient focal neurological deficit that lasted less than 24 hours and thought to be vascular in origin)
  • emergency/urgent surgery (i.e. surgery which must be undertaken within 24 hours of acute presentation to hospital)
  • high-risk type of surgery (i.e. intrathoracic or intraperitoneal)

Exclusion Criteria

  • having cardiac surgery
  • marked impairment of gas-exchange expected to require Fi02> 0.5 intraoperatively
  • specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure) or the anaesthetist plans to use supplemental oxygen (eg. colorectal surgery)
  • N2O unavailable for use.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00430989). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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