Back to results

International Substudy Enigma2 on Postoperative Cognitive Disorders (ISEP)

Primary Purpose

Anesthesia, Delirium, Dementia, Amnestic, Cognitive Disorders

Status

Terminated

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Nitrous Oxide

Placebo

About this trial

This is an interventional treatment trial for Anesthesia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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:

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

Sites / Locations

The Chinese University of Hong Kong Prince of Wales Hospital
Geneva University Hospitals

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Nitrous Oxide

Air/Oxygen (placebo)

Arm Description

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

Receives a mixture of 70% Air in 30% Oxygen

Outcomes

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

ICU stay

Planned and unplanned admission to the ICU and ICU duration of stay; Follow up to be performed for the whole duration of hospital stay and up to a maximum of 3 months

Hospital stay

Duration of stay in Hospital; Follow up to be performed for the whole duration of hospital stay and up to a maximum of 3 months

Quality of life

Use of the validated EuroQol test (EQ-5D questionnaire http://www.euroqol.org/)

Full Information

NCT ID

NCT02489097

First Posted

June 26, 2015

Last Updated

December 12, 2020

Sponsor

University Hospital, Geneva

Collaborators

Prince of Wales Hospital, Shatin, Hong Kong, Chinese University of Hong Kong

1. Study Identification

Unique Protocol Identification Number

NCT02489097

Brief Title

International Substudy Enigma2 on Postoperative Cognitive Disorders

Acronym

ISEP

Official Title

Evaluating the Incidence and Association Between Nitrous Oxide and Postoperative Cognitive Disorders in Anaesthesia

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Terminated

Why Stopped

Interim analysis results showed futility

Study Start Date

September 2013 (Actual)

Primary Completion Date

May 2016 (Actual)

Study Completion Date

May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Geneva

Collaborators

Prince of Wales Hospital, Shatin, Hong Kong, Chinese University of Hong Kong

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anesthesia, Delirium, Dementia, Amnestic, Cognitive Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

140 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nitrous Oxide

Arm Type

Active Comparator

Arm Description

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

Arm Title

Air/Oxygen (placebo)

Arm Type

Placebo Comparator

Arm Description

Receives a mixture of 70% Air in 30% Oxygen

Intervention Type

Drug

Intervention Name(s)

Nitrous Oxide

Other Intervention Name(s)

N2O

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Air/Oxygen

Intervention Description

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

Primary Outcome Measure Information:

Title

Memory, Executive function, Attention and psychomotor speed testing battery

Description

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

Time Frame

Baseline before surgery

Title

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

Description

Time Frame

First assessment (7 days)

Title

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

Description

Time Frame

Second assessment (3 months)

Secondary Outcome Measure Information:

Title

ICU stay

Description

Planned and unplanned admission to the ICU and ICU duration of stay; Follow up to be performed for the whole duration of hospital stay and up to a maximum of 3 months

Time Frame

up to a maximum of 3 months

Title

Hospital stay

Description

Duration of stay in Hospital; Follow up to be performed for the whole duration of hospital stay and up to a maximum of 3 months

Time Frame

up to a maximum of 3 months

Title

Quality of life

Description

Use of the validated EuroQol test (EQ-5D questionnaire http://www.euroqol.org/)

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Myles Paul, MD, FANZCA

Organizational Affiliation

Bayside Health

Official's Role

Study Chair

Facility Information:

Facility Name

The Chinese University of Hong Kong Prince of Wales Hospital

City

Hong Kong

State/Province

Hong Kong

Country

China

Facility Name

Geneva University Hospitals

City

Geneva

ZIP/Postal Code

1203

Country

Switzerland

12. IPD Sharing Statement

Citations:

PubMed Identifier

21889262

Citation

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.

Results Reference

result

PubMed Identifier

18813051

Citation

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.

Results Reference

result

PubMed Identifier

17667565

Citation

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.

Results Reference

result

Learn more about this trial

International Substudy Enigma2 on Postoperative Cognitive Disorders

We'll reach out to this number within 24 hrs