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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
29/09/2005
Type of registration
Retrospectively 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
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

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
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
Secondary outcome [2] 1801 0
2. Wound infection
Timepoint [2] 1801 0
Secondary outcome [3] 1802 0
3. Severe vomiting
Timepoint [3] 1802 0
Secondary outcome [4] 1803 0
4. Quality of recovery
Timepoint [4] 1803 0
Secondary outcome [5] 1804 0
5. ICU length of stay
Timepoint [5] 1804 0
Secondary outcome [6] 1805 0
6. 30-day mortality
Timepoint [6] 1805 0

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
Gender
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
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 836 0
Government body
Name [1] 836 0
NHMRC research grant
Address [1] 836 0
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
Approval date [1] 2098 0
Ethics approval number [1] 2098 0

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
Public notes

Contacts
Principal investigator
Name 36367 0
Address 36367 0
Country 36367 0
Phone 36367 0
Fax 36367 0
Email 36367 0
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
p.myles@alfred.org.au
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
j.hunt@alfred.org.au

No information has been provided regarding IPD availability
Summary results
No Results