Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000279729
Ethics application status
Approved
Date submitted
21/01/2022
Date registered
15/02/2022
Date last updated
15/02/2022
Date data sharing statement initially provided
15/02/2022
Date results information initially provided
15/02/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Postoperative pulmonary complications in the ENIGMA 2 Trial
Scientific title
Postoperative pulmonary complications (atelectasis and pneumonia) in the ENIGMA 2 Trial
Secondary ID [1] 306207 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
This is a follow up study of the ENIGMA 2 Trial NCT00430989

Health condition
Health condition(s) or problem(s) studied:
Postoperative pulmonary complications 324917 0
Condition category
Condition code
Respiratory 322351 322351 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study is investigating additional postoperative patient outcomes within 30 days of index suergy in pre-existing patients who were recruited to the ENIGMA 2 Trial (which was conducted between May 30, 2008 and Sept 28, 2013), which did not collect pulmonary complications data at the time of the trial. Data collection for the study involves retrospective inspection of individual patient hospital medical records from the index hospital admission and surgery, to collect the required data on postoperative pulmonary complications following the index surgery. The trial intervention group received 70% nitrous oxide in oxygen inspired in the breathing circuit as part of inhalational general anaesthesia, delivered from post-induction of anaesthesia until end of surgery. The N2O concentration could be adjusted if the FIO2 is required to be increased due to arterial oxygen saturation measurements on the judgement of the attending anaesthetist.
Intervention code [1] 322610 0
Not applicable
Comparator / control treatment
The control group in the ENIGMA 2 trial received 30% oxygen in air inspired in the breathing circuit as part of inhalational general anaesthesia, delivered from post-induction of anaesthesia until end of surgery. The FIO2 could be increased if required due to arterial oxygen saturation measurements on the judgement of the attending anaesthetist.
Control group
Active

Outcomes
Primary outcome [1] 330116 0
Postoperative pulmonary atelectasis, confirmed by chest radiology report, recorded on the patients electronic hospital medical record within 30 days of their index surgery for the ENIGMA 2 Trial, extracted using data-linkage to medical records, with no active participant involvement.
Timepoint [1] 330116 0
Up to 30 days postoperative
Secondary outcome [1] 404939 0
Postoperative pneumonia, confirmed by the presence of a diagnostic pulmonary infiltrate on chest radiology report, along with one or more of a blood WCC >/= 12,000/mL, temperature >/= 38C, or positive sputum microbiological culture, recorded on the patients electronic hospital medical record within 30 days of their index surgery for the ENIGMA 2 Trial, extracted using data-linkage to medical records, with no active participant involvement.
Timepoint [1] 404939 0
Up to 30 days postoperative

Eligibility
Key inclusion criteria
Participants randomised to the ENIGMA 2 Trial within Australia, according to the ENIGMA 2 inclusion criteria:
Adult males and females age >/= 45 years, undergoing noncardiac surgery and general anaesthesia expected to exceed two hours.
At increased risk of cardiac events, defined as any of
history of coronary artery disease as defined by a history of any one of the following: i. angina ii. MI iii. segmental wall motion abnormality on echocardiography or a fixed defect on radionuclide imaging iv. a positive exercise stress test for cardiac ischaemia v. a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test for cardiac ischaemia vi. coronary revascularization (CABG or PTCA) vii. angiographic evidence of atherosclerotic stenosis > 50% of the diameter of any coronary artery viii. ECG with pathological Q waves in two contiguous leads
heart failure
cerebrovascular disease thought due to atherothrombotic disease
aortic or peripheral vascular disease
or three or more of the following risk factors:
age >/=70 years
any history of congestive heart failure
diabetes and currently on an oral hypoglycaemic agent or insulin therapy
current treatment for hypertension
preoperative serum creatinine >175 micro mol/L (> 2.0 mg/dl)
current or previous high cholesterol >6.2 mmol/L (> 240 mg/dl)
history of a transient ischemic attack (TIA) (i.e. a transient focal neurological deficit that lasted less than 24 hours and thought to be vascular in origin)
emergency/urgent surgery (i.e. surgery which must be undertaken within 24 hours of acute presentation to hospital) high-risk type of surgery (i.e. intrathoracic or intraperitoneal)
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
having cardiac surgery
marked impairment of gas-exchange expected to require Fi02> 0.5 intraoperatively
specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure) or the anaesthetist plans to use supplemental oxygen (eg. colorectal surgery)
N2O unavailable for use.

Study design
Purpose
Duration
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Primary and secondary endpoint statistical comparisons were done using the Chi-square test.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
1/12/2018
Date of last participant enrolment
Anticipated
Actual
2/02/2022
Date of last data collection
Anticipated
31/03/2022
Actual
Sample size
Target
2325
Accrual to date
Final
2325
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 21475 0
The Alfred - Melbourne
Recruitment hospital [2] 21476 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [3] 21477 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [4] 21478 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 21479 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [6] 21480 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [7] 21481 0
Royal Perth Hospital - Perth
Recruitment hospital [8] 21482 0
Westmead Hospital - Westmead
Recruitment hospital [9] 21483 0
Fremantle Hospital and Health Service - Fremantle
Recruitment postcode(s) [1] 36379 0
3004 - Melbourne
Recruitment postcode(s) [2] 36380 0
3052 - Parkville
Recruitment postcode(s) [3] 36381 0
3065 - Fitzroy
Recruitment postcode(s) [4] 36382 0
3084 - Heidelberg
Recruitment postcode(s) [5] 36383 0
3168 - Clayton
Recruitment postcode(s) [6] 36384 0
3175 - Dandenong
Recruitment postcode(s) [7] 36385 0
6000 - Perth
Recruitment postcode(s) [8] 36386 0
2145 - Westmead
Recruitment postcode(s) [9] 36387 0
6160 - Fremantle

Funding & Sponsors
Funding source category [1] 310556 0
Other
Name [1] 310556 0
Dept of Anaesthesia, Austin Health
Country [1] 310556 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Studley Rd
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 311728 0
None
Name [1] 311728 0
Address [1] 311728 0
Country [1] 311728 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310165 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 310165 0
Studley Rd
Heidelberg VIC 3084
Ethics committee country [1] 310165 0
Australia
Date submitted for ethics approval [1] 310165 0
Approval date [1] 310165 0
07/11/2018
Ethics approval number [1] 310165 0
HREC/46023/Austin-2018

Summary
Brief summary
The ENIGMA (Evaluation of Nitrous oxide In the Gas Mixture in Anaesthesia) Trial was a large (n = 2,050) pragmatic multicentre randomised trial in patients undergoing major surgery. The incidence of clinically significant postoperative pulmonary complications (PPCs) measured by routine chest radiography and postoperative full blood and microbiology testing, as well a septic complications, were found to be increased with N2O. The larger ENIGMA 2 Trial (n = 7,000) did not confirm the findings of ENIGMA that N2O increased rates of wound infection or sepsis. Unfortunately, ENIGMA 2 did not prospectively collect data on pulmonary complications. Given the pragmatic nature of the protocol for measurement of PPC incidence used in ENIGMA, it was seen as feasible to replicate it post hoc in the ENIGMA 2 trial sample, using data collected as part of routine postoperative clinical management in these patients. This was done in the cohort of patients recruited to the ENIGMA 2 Trial within Australia, which consisted of over 2,500 patients or approximately 35% of total trial recruitment.
Trial website
Trial related presentations / publications
Public notes
This is a retrospective study of data on pulmonary complications collected in patients recruited to the ENIGMA 2 Trial, between 2007-13.

Contacts
Principal investigator
Name 116718 0
Prof Philip Peyton
Address 116718 0
Dept of Anaesthesia
Austin Health
Studley Rd
Heidelberg
VIC 3084
Country 116718 0
Australia
Phone 116718 0
+61 3 94965000
Fax 116718 0
Email 116718 0
[email protected]
Contact person for public queries
Name 116719 0
Prof Philip Peyton
Address 116719 0
Dept of Anaesthesia
Austin Health
Studley Rd
Heidelberg
VIC 3084
Country 116719 0
Australia
Phone 116719 0
+61 3 94965000
Fax 116719 0
Email 116719 0
[email protected]
Contact person for scientific queries
Name 116720 0
Prof Philip Peyton
Address 116720 0
Dept of Anaesthesia
Austin Health
Studley Rd
Heidelberg
VIC 3084
Country 116720 0
Australia
Phone 116720 0
+61 3 94965000
Fax 116720 0
Email 116720 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Primary and secondary endpoint data
When will data be available (start and end dates)?
31/12/2022 after publication of results, available for 5 years.
Available to whom?
Please contact the Principal Investigator to discuss
Available for what types of analyses?
Please contact the Principal Investigator to discuss
How or where can data be obtained?
Please contact the Principal Investigator to discuss: phil.peyton@austin .org.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14659Study protocol    Please contact the Principal Investigator to discu... [More Details]
14660Ethical approval    Please contact the Principal Investigator to discu... [More Details]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.