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

Sponsors and Collaborators:	Bayside Health National Health and Medical Research Council, Australia
Information provided by:	Bayside Health
ClinicalTrials.gov Identifier:	NCT00430989

Purpose

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

Condition	Intervention	Phase
Coronary Artery Disease	Drug: Nitrous Oxide	Phase IV

MedlinePlus related topics: Anesthesia Coronary Artery Disease Pulmonary Embolism Surgery

Drug Information available for: Nitrous oxide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Large, Randomised, Parallel-Group, Controlled Trial, With Patients Randomly Allocated to Either N2O-Containing (70% N2O in Oxygen [FiO2 0.3]) or N2O-Free (70% Nitrogen in Oxygen [FiO2 0.3]).

Further study details as provided by Bayside Health:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

Myocardial Infarction (MI)
Cardiac failure
Cardiac arrest
Pulmonary embolism
Stroke
Wound infection
Hospital Stay

Estimated Enrollment:	7000
Study Start Date:	April 2007
Estimated Study Completion Date:	April 2012

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult males and females, 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 any one of the following:
  - angina
  - MI
  - CABG or PTCA
  - documentation on nuclear stress testing or angiography
  - ECG with pathological Q waves in two contiguous leads
- Heart failure
- Cerebrovascular disease;
- Vascular disease
- Or two or more of the following risk factors:
  - age ≥65 years
  - diabetes
  - hypertension
  - cholesterol ≥6.2 mmol/L
  - non-elective surgery

Exclusion Criteria:

Cardiac surgery
Not expected to survive 30 days (eg. ASA 5)
Marked impairment of gas-exchange (requiring Fi02> 0.5
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430989

Contacts

Contact: Ornella Clavissi	+61 3 8517 5326	oclavisi@anzca.edu.au
Contact: Sophie Wallace	+61 39076 2000	sophia.wallace@alfred.org.au

Locations

Australia, Victoria
Alfred Hosptial
Melbourne, Victoria, Australia, 3004

Sponsors and Collaborators

Bayside Health

National Health and Medical Research Council, Australia

Investigators

Principal Investigator:

Paul S Myles, MBBS MPH MD

The Alfred

More Information

No publications provided

Study ID Numbers:	6/07
Study First Received:	January 31, 2007
Last Updated:	February 1, 2007
ClinicalTrials.gov Identifier:	NCT00430989 History of Changes
Health Authority:	Australia: Human Research Ethics Committee

Keywords provided by Bayside Health:

Anaesthesia
Major Surgery
Coronary artery disease

Nitrous oxide
Effects of Nitrous Oxide following Anaesthesia
Anaesthesia and coronary artery disease

Study placed in the following topic categories:

Arterial Occlusive Diseases
Heart Diseases
Myocardial Ischemia
Nitrous Oxide
Vascular Diseases
Central Nervous System Depressants
Anesthetics
Ischemia

Arteriosclerosis
Coronary Disease
Anesthetics, Inhalation
Anesthetics, General
Analgesics, Non-Narcotic
Analgesics
Peripheral Nervous System Agents
Coronary Artery Disease

Additional relevant MeSH terms:

Arterial Occlusive Diseases
Heart Diseases
Myocardial Ischemia
Nitrous Oxide
Physiological Effects of Drugs
Vascular Diseases
Central Nervous System Depressants
Anesthetics
Arteriosclerosis
Pharmacologic Actions
Coronary Disease

Anesthetics, Inhalation
Anesthetics, General
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Cardiovascular Diseases
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Coronary Artery Disease

ClinicalTrials.gov processed this record on May 07, 2009