International Substudy Enigma2 on Postoperative Cognitive Disorders

NCT ID: NCT02489097

Last Updated: 2020-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2016-05-31

Brief Summary

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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.

Detailed Description

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Numerous studies questioned the routine use of nitrous oxide (N2O), the oldest anaesthetic agent used since the development of anaesthesia care. Despite its wide use, there is sufficient doubt as to the risk-benefit profile.

There is strong evidence that N2O is a major risk factor for postoperative nausea and vomiting. It is clear that (even) brief exposure to N2O impairs methionine synthetase, an enzyme required for DNA production, red and white blood cell formation. Tissue hypoxia may be more common. These adverse effects are enhanced in "sick" patients (ie. those at highest risk, with increased hospital length of stay and healthcare expenditure), and will be more likely in longer surgery. At the same time, observational studies and subgroup analysis of published trials suggest that N2O may have beneficial effects in preventing pain and postoperative cognitive disorders

Outcome trial data on postoperative cognitive disorders are lacking in this area for an anaesthetic gas used in more than 90% of all surgery around the world. The enigma2 substudy as a nested study of the large Enigma2 randomised controlled trial aims at answering this question.

The investigators aim at recruiting 420 patients in 2 of the 25 centres participating to the Enigma 2 trials, who are undergoing major surgery.

Conditions

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Anesthesia Delirium, Dementia, Amnestic, Cognitive Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Nitrous Oxide

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

Group Type ACTIVE_COMPARATOR

Nitrous Oxide

Intervention Type DRUG

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

Air/Oxygen (placebo)

Receives a mixture of 70% Air in 30% Oxygen

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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Nitrous Oxide

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

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Other Intervention Names

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N2O Air/Oxygen

Eligibility Criteria

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Inclusion Criteria

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

OR

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),

Exclusion Criteria

1. Dementia (MMS test≤24)
2. Parkinson Disease
3. Patients taking regularly (\>2 weeks) tricyclic antidepressants or neuroleptics
4. Patients suffering from Alcohol Dependency (WHO CRITERIA )
5. Patients suffering from severe hypoacusis or visual loss or any other reason hindering the CANTAB battery testing process
6. Patients with untreated deficit in Vitamin B6, B12 and folic acid
7. Patients with marked impairment of gas-exchange requiring Fi02\> 0.5 intraoperatively
8. 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)
9. N2O unavailable
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prince of Wales Hospital, Shatin, Hong Kong

OTHER

Sponsor Role collaborator

Chinese University of Hong Kong

OTHER

Sponsor Role collaborator

University Hospital, Geneva

OTHER

Sponsor Role lead

Responsible Party

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Dr Guy Haller

Staff Anaesthetist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Myles Paul, MD, FANZCA

Role: STUDY_CHAIR

Bayside Health

Locations

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The Chinese University of Hong Kong Prince of Wales Hospital

Hong Kong, Hong Kong, China

Site Status

Geneva University Hospitals

Geneva, , Switzerland

Site Status

Countries

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China Switzerland

References

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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.

Reference Type RESULT
PMID: 21889262 (View on PubMed)

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.

Reference Type RESULT
PMID: 18813051 (View on PubMed)

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.

Reference Type RESULT
PMID: 17667565 (View on PubMed)

Other Identifiers

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Enigma II nested NCT00430989

Identifier Type: OTHER

Identifier Source: secondary_id

NAC 08-021

Identifier Type: -

Identifier Source: org_study_id