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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02489097




Registration number
NCT02489097
Ethics application status
Date submitted
26/06/2015
Date registered
2/07/2015
Date last updated
16/12/2020

Titles & IDs
Public title
International Substudy Enigma2 on Postoperative Cognitive Disorders
Scientific title
Evaluating the Incidence and Association Between Nitrous Oxide and Postoperative Cognitive Disorders in Anaesthesia
Secondary ID [1] 0 0
Enigma II nested NCT00430989
Secondary ID [2] 0 0
NAC 08-021
Universal Trial Number (UTN)
Trial acronym
ISEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anesthesia 0 0
Delirium, Dementia, Amnestic, Cognitive Disorders 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Other mental health disorders
Mental Health 0 0 0 0
Learning disabilities
Neurological 0 0 0 0
Dementias
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nitrous Oxide
Other interventions - Placebo

Active Comparator: Nitrous Oxide - Receives a mixture of 70% Nitrous Oxide in 30% Oxygen

Placebo Comparator: Air/Oxygen (placebo) - Receives a mixture of 70% Air in 30% Oxygen


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

Other interventions: Placebo
Administration of a concentration of 70% Air with 30% Oxygen in the anaesthetic gas mixture
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Memory, Executive function, Attention and psychomotor speed testing battery
Timepoint [1] 0 0
Baseline before surgery
Primary outcome [2] 0 0
Memory, Executive function, Attention and psychomotor speed using CANTAB Cognitive testing battery at 7days following surgery
Timepoint [2] 0 0
First assessment (7 days)
Primary outcome [3] 0 0
Memory, Executive function, Attention and psychomotor speed using CANTAB Cognitive testing battery at 3 months following surgery
Timepoint [3] 0 0
Second assessment (3 months)
Secondary outcome [1] 0 0
ICU stay
Timepoint [1] 0 0
up to a maximum of 3 months
Secondary outcome [2] 0 0
Hospital stay
Timepoint [2] 0 0
up to a maximum of 3 months
Secondary outcome [3] 0 0
Quality of life
Timepoint [3] 0 0
3 months

Eligibility
Key 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),
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2016
Sample size
Target
Accrual to date
Final
140
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Hong Kong
Country [2] 0 0
Switzerland
State/province [2] 0 0
Geneva

Funding & Sponsors
Primary sponsor type
Other
Name
University Hospital, Geneva
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Prince of Wales Hospital, Shatin, Hong Kong
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Chinese University of Hong Kong
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02489097
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Myles Paul, MD, FANZCA
Address 0 0
Bayside Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02489097