Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12605000555651
Ethics application status
Approved
Date submitted
26/09/2005
Date registered
29/09/2005
Date last updated
19/05/2020
Date data sharing statement initially provided
19/05/2020
Date results information initially provided
19/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia
Scientific title
A randomised controlled trial to evaluate the effect of Nitrous Oxide on Endothelial Dysfunction after noncardiac surgery
Secondary ID [1] 301327 0
nil known
Universal Trial Number (UTN)
Trial acronym
ENIGMA II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The effect of Nitrous Oxide on endothelial function for patients having elective surgery of 2 hour or more duration. 680 0
Condition category
Condition code
Other 755 755 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients consenting to the trial will have baseline and day 1 postoperative measurements of their endothelial functioning on one arm.

Preoperatively : A blood pressure cuff is inflated on the upper arm and an ultrasound is taken of the blood vessels in the arm as the cuff is deflated. Blood tests are taken for folate, homocysteine, arginine, citrulline, ADMA and nitrate.

Intraoperatively : Patients will be randomly allocated to either 70% N2O in oxygen (FiO2 0.3) or oxygen with or without nitrogen (FiO2 0.8-1.0).

Postoperatively : Patients will have the ultrasound on the same arm as preoperatively and blood tests will be done again. Half of the patients will have received nitrous oxide for a minimum of 2 hours and the other half only oxygen.
Intervention code [1] 678 0
Treatment: Drugs
Comparator / control treatment
N2O
Control group
Dose comparison

Outcomes
Primary outcome [1] 943 0
Hypothesis: In patients undergoing anaesthesia for major surgery, avoidance of N2O will ablate endothelial dysfunction at 24 hours after noncardiac surgery when compared with otherwise identically managed surgical patients receiving N2O as a component of their anaesthesia. Primary Endpoint 1. Endothelial dysfunction at 24 hours after surgery, as measured by flow-mediated vasodilatation
Timepoint [1] 943 0
Measured at 24 hours after surgery.
Secondary outcome [1] 1800 0
1. Hospital length of stay (LOS)
Timepoint [1] 1800 0
30 days
Secondary outcome [2] 1801 0
2. Wound infection
Timepoint [2] 1801 0
30 days
Secondary outcome [3] 1802 0
3. Severe vomiting
Timepoint [3] 1802 0
3 days
Secondary outcome [4] 1803 0
4. Quality of recovery
Timepoint [4] 1803 0
3 days
Secondary outcome [5] 1804 0
5. ICU length of stay
Timepoint [5] 1804 0
30 days
Secondary outcome [6] 1805 0
6. 30-day mortality
Timepoint [6] 1805 0
30 days

Eligibility
Key inclusion criteria
1. Any risk factors for arteriosclerosis (eg. hypertension, diabetes, age >60 yrs, coronary artery disease). 2. Planned general anaesthesia for surgery that includes a skin incision and expected to exceed two hours, and the patient is expected to be in hospital for at least three days.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Endoscopic or radiological procedures 2. Cardiac surgery3. Marked impairment of gas-exchange (requiring Fi02> 0.3)4. Thoracic surgery requiring one-lung ventilation (requiring Fi02> 0.3)5. Specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure)6. Lack of provision of N2O.7. Patients considered to be at high-risk for PONV8. Patients considered to be at high-risk for wound infection.

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)
Randomisation is concealed using opaque sealed envelopes. The envelopes contain dark paper on which the allocation is written in pale writing to avoid being revealed were someone to raise it to bright light.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation is done using a computer generated random list allocated by opaque sealed envelopes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2005
Actual
9/06/2008
Date of last participant enrolment
Anticipated
Actual
1/12/2008
Date of last data collection
Anticipated
Actual
15/11/2010
Sample size
Target
220
Accrual to date
Final
220
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 836 0
Government body
Name [1] 836 0
NHMRC research grant
Country [1] 836 0
Australia
Primary sponsor type
Government body
Name
NHMRC
Address
Country
Australia
Secondary sponsor category [1] 703 0
Hospital
Name [1] 703 0
The Alfred
Address [1] 703 0
Country [1] 703 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2098 0
The Alfred
Ethics committee address [1] 2098 0
Melbourne
Ethics committee country [1] 2098 0
Australia
Date submitted for ethics approval [1] 2098 0
16/02/2007
Approval date [1] 2098 0
Ethics approval number [1] 2098 0
Ethics committee name [2] 306034 0
Alfred Hospital Ethics committee
Ethics committee address [2] 306034 0
Commercial road Melbourne 3004 Vic
Ethics committee country [2] 306034 0
Australia
Date submitted for ethics approval [2] 306034 0
01/01/2007
Approval date [2] 306034 0
16/02/2007
Ethics approval number [2] 306034 0
08/07

Summary
Brief summary
Patients consenting to the trial will have baseline and day 1 postoperative measurements of their endothelial functioning on one arm.

Preoperatively : A blood pressure cuff is inflated on the upper arm and an ultrasound is taken of the blood vessels in the arm as the cuff is deflated. Blood tests are taken for folate, homocysteine, arginine, citrulline, ADMA and nitrate.

Intraoperatively : Patients will be randomly allocated to either 70% N2O in oxygen (FiO2 0.3) or oxygen with or without nitrogen (FiO2 0.8-1.0).

Postoperatively : Patients will have the ultrasound on the same arm as preoperatively and blood tests will be done again. Half of the patients will have received nitrous oxide for a minimum of 2 hours and the other half only oxygen.
Trial website
Trial related presentations / publications
McIlroy DR, Chan MT, Wallace SK, Symons JA, Koo EG, Chu LC, Myles PS. Automated preoperative assessment of endothelial dysfunction and risk stratification for perioperative myocardial injury in patients undergoing non-cardiac surgery. Lancet. 2014 Oct 18;384(9952):1446-54.
Public notes

Contacts
Principal investigator
Name 36367 0
Prof Paul Myles
Address 36367 0
Director, Dept of Anaesthesiology and Perioperative Medicine
Alfred Hospital and Monash University, Melbourne, vic 3004
Country 36367 0
Australia
Phone 36367 0
+61 390763176
Fax 36367 0
Email 36367 0
[email protected]
Contact person for public queries
Name 9867 0
Paul Myles
Address 9867 0
Professor / Director
Department of Anaeshesia and Perioperative Medicine
The Alfred
Commercial Road
Melbourne VIC 3004
Country 9867 0
Australia
Phone 9867 0
+61 3 92763176
Fax 9867 0
+61 3 92071076
Email 9867 0
[email protected]
Contact person for scientific queries
Name 795 0
Jennifer Hunt
Address 795 0
Research Manager
Department of Anaeshesia and Perioperative Medicine
The Alfred
Commercial Road
Melbourne VIC 3004
Country 795 0
Australia
Phone 795 0
+61 3 92762648
Fax 795 0
+61 3 92071076
Email 795 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Myles Paul S, Peyton Philip, Silbert Brendan, Hunt... [More Details]

Documents added automatically
No additional documents have been identified.