International Substudy Enigma2 on Postoperative Cognitive Disorders

NCT02489097 | Terminated Phase 4 DMC

• 2 other identifiers: NAC 08-021Enigma II nested NCT00430989
• Study Type: interventional
• Target: 140
• Locations: 2 countries
• Sites: 2

Brief Summary

The study is a substudy of the Enigma2 trial (NCT00430989) which aims at investigating the effectiveness and safety of nitrous oxide (N2O) in anaesthesia.The substudy focus is on postoperative cognitive disorders. Substudy Hypothesis: In patients undergoing anaesthesia for major surgery, administration of N2O will reduce postoperative cognitive disorders when compared with otherwise identically managed surgical patients not receiving N2O as a component of their anaesthesia.

Conditions

Anesthesia; Delirium, Dementia, Amnestic, Cognitive Disorders

Outcome Measures

Primary Outcomes (3)

• Memory, Executive function, Attention and psychomotor speed testing battery

  Validated Computerized testing battery developed by the University of Cambridge for cognitive testing (CANTAB). Patients are tested for baseline cognitive function before surgery

  Baseline before surgery

• Memory, Executive function, Attention and psychomotor speed using CANTAB Cognitive testing battery at 7days following surgery

  Validated Computerized testing battery developed by the University of Cambridge for cognitive testing (CANTAB). Patients are tested for changes from the baseline cognitive function (before surgery) at 7 days after surgery

  First assessment (7 days)

• Memory, Executive function, Attention and psychomotor speed using CANTAB Cognitive testing battery at 3 months following surgery

  Validated Computerized testing battery developed by the University of Cambridge for cognitive testing (CANTAB). Patients are tested for changes from the baseline cognitive function (before surgery) at 3 months after surgery

  Second assessment (3 months)

Secondary Outcomes (3)

• ICU stay

  up to a maximum of 3 months

• Hospital stay

  up to a maximum of 3 months

• Quality of life

  3 months

Study Arms (2)

Nitrous Oxide

ACTIVE COMPARATOR

Receives a mixture of 70% Nitrous Oxide in 30% Oxygen

Drug: Nitrous Oxide

Air/Oxygen (placebo)

PLACEBO COMPARATOR

Receives a mixture of 70% Air in 30% Oxygen

Other: Placebo

Interventions

Nitrous Oxide DRUG

Administration of a concentration of 70% Nitrous Oxide with 30% Oxygen in the anaesthetic gas mixture

Also known as: N2O

Nitrous Oxide

Placebo OTHER

Administration of a concentration of 70% Air with 30% Oxygen in the anaesthetic gas mixture

Also known as: Air/Oxygen

Air/Oxygen (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males and females aged ≥ 45 years, undergoing noncardiac surgery and general anaesthesia that exceeds two hours.
• At increased risk of cardiac events, defined as any of:
• history of coronary artery disease (angina, MI, Coronary revascularisation-Coronary Artery Bypass Graft (CABG) and Percutaneous Transluminal Coronary Angiography ( PTCA)-, positive stress testing, angiography/other imaging, Q waves on ECG)
• heart failure
• cerebrovascular disease due to atherothrombotic disease
• aortic or peripheral vascular disease
• three or more of the following risk factors: age ≥70 years, history of heart failure, diabetes (medicated), hypertension (medicated), preoperative serum creatinine \>175 mmol/L, cholesterol ≥6.2 mmol/L, history of a transient ischemic attack (TIA),

You may not qualify if:

• Dementia (MMS test≤24)
• Parkinson Disease
• Patients taking regularly (\>2 weeks) tricyclic antidepressants or neuroleptics
• Patients suffering from Alcohol Dependency (WHO CRITERIA )
• Patients suffering from severe hypoacusis or visual loss or any other reason hindering the CANTAB battery testing process
• Patients with untreated deficit in Vitamin B6, B12 and folic acid
• Patients with marked impairment of gas-exchange requiring Fi02\> 0.5 intraoperatively
• Patients with specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure) or the use of supplemental oxygen is planned (eg. colorectal surgery)
• N2O unavailable

Sponsors & Collaborators

• University Hospital, Geneva: lead
• Prince of Wales Hospital, Shatin, Hong Kong: collaborator
• Chinese University of Hong Kong: collaborator

Study Sites (2)

The Chinese University of Hong Kong Prince of Wales Hospital

Hong Kong, Hong Kong, China

Location

Geneva University Hospitals

Geneva, 1203, Switzerland

Location

Related Publications (3)

• Chan MTV, Wan ACM, Gin T, Leslie K, Myles PS. Chronic postsurgical pain after nitrous oxide anesthesia. Pain. 2011 Nov;152(11):2514-2520. doi: 10.1016/j.pain.2011.07.015. Epub 2011 Sep 1.

  PMID: 21889262 RESULT

• Sanders RD, Weimann J, Maze M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology. 2008 Oct;109(4):707-22. doi: 10.1097/ALN.0b013e3181870a17.

  PMID: 18813051 RESULT

• Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe E; ENIGMA Trial Group. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology. 2007 Aug;107(2):221-31. doi: 10.1097/01.anes.0000270723.30772.da.

  PMID: 17667565 RESULT

MeSH Terms

Conditions

Neurocognitive Disorders

Interventions

Nitrous Oxide

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds

Study Officials

• Myles Paul, MD, FANZCA

  Bayside Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Anaesthetist

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: July 2, 2015
• Study Start: September 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: December 16, 2020

Record last verified: 2020-12

Locations

CN (1); CH (1)