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Trial registered on ANZCTR


Registration number
ACTRN12616000873426
Ethics application status
Approved
Date submitted
30/06/2016
Date registered
4/07/2016
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does measuring pre-surgery brain oxygen levels in sick elderly patients coming in for major elective non-cardiac surgery allow us to predict who will have more complications, including death, major organ failure, and post-operative delirium
Scientific title
The Use of Preoperative cerebral tissue saturation (ScO2) to Stratify Cardiovascular Risk in High Risk Elderly Patients admitted for Major Non-Cardiac Surgery
Secondary ID [1] 289579 0
none
Universal Trial Number (UTN)
Trial acronym
The PROXi Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
outcomes after major surgery 299317 0
Condition category
Condition code
Neurological 299310 299310 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Prospective, multicentre, double blinded, observational study. Participants are elderly patients greater than or equal to 60 years old, American Society of Anesthesiologists (ASA) 3 or 4, elective major non-cardiac surgery anticipated to last for greater than or equal to 2 hours, receiving a general with or without regional anaesthesia. Pre-operative characteristics such as gender, age, body mass index, Charlson score, co-morbidities, medication history, haemoglobin, creatinine, and albumin levels will be collected in the pre-anaesthesia clinic. Cerebral oximetry will be placed on the patient's forehead to collect ScO2 values from both cerebral hemispheres. These are measured using non-invasive electrodes with embedded near-infrared light sensors. Baseline ScO2 is taken at room air, at rest, and supplemented ScO2 is taken after breathing 6L/min oxygen delivered by Hudson mask after 5 minutes. This is performed by a researcher trained in correctly applying the cerebral oximetry sensors on patients' heads. This baseline measurement can occur in the pre-anaesthetic clinic or anaesthetic bay, up to 4 weeks prior to surgery.
This is a pragmatic study and there is no change to the intra-operative anaesthesia or surgical management.
Intra-operative data collected includes blood loss, doses of anaesthesia medications, opioid use, use of local anaesthetics, vasopressor use and duration of surgery.
Patients will be followed up for 30 days after surgery for the following primary and secondary outcomes:
1. Major Adverse Events (MAE) which includes: all cause death, acute myocardial infarction, cardiac arrest, stroke, pulmonary embolism, acute kidney injury, sepsis
2. Number of post-operative days of delirium, measured using the Confusion Assessment Method (CAM) questionnaire.
All post-operative data will be collected by blinded researchers, through direct ward follow up of patients, telephone follow up at 30 days if already discharged from hospital, liaison with the patient's relatives, surgical team or local general practitioner, or if deceased, postmortem results from hospital medical records.
Intervention code [1] 295181 0
Early Detection / Screening
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298797 0
Major Adverse Events: mortality all cause, and any of the following morbidity events. Outcomes are assessed by review of the medical records. (1) acute myocardial infarction, defined by a typical rise in troponin level, or typical fall in elevated troponin, or rapid rise and fall of creatine kinase MB isoenzyme. In addition, one of the following is required: ischaemic symptoms, pathological Q waves, electrocardiographic evidence of ischaemia, coronary artery revascularisation procedure, or new regional wall motion abnormality on echocardiography or mibi scan; (2) cardiac arrest, defined as successful resuscitation from either documented or presumed ventricular fibrillation, sustained ventricular tachycardia, or asystole; (3) stroke, defined as cerebral infarction or haemorrhage on computed tomography or magnetic resonance imaging scan, or new neurological signs lasting more than 24 hours; (4) pulmonary embolism, defined as a high probability ventilation-perfusion scan, positive spiral computed tomography or positive pulmonary angiography; (5) Acute kidney injury, defined as meeting criteria for at least RIFLE class 1 injury, with greater than or equal to 2 fold increase in serum creatinine from pre-operative baseline, or estimated glomerular filtration rate decrease of greater than or equal to 50% from baseline, or urine output less than or equal to 0.5ml/kg/hr for 12 hours; (6) sepsis, meeting the definition of greater than or equal to 2 on the Sequential Organ Failure Assessment scale.
Timepoint [1] 298797 0
30-days postoperative
Secondary outcome [1] 325234 0
Number of days of postoperative delirium, as measured using the CAM questionnaire.
Timepoint [1] 325234 0
CAM will be administered daily commencing on Day 1 postoperative and will conclude on reaching any of the following, whichever occurs first:
- 2 consecutive delirium-free post-operative days
- death
- 30th consecutive day as an inpatient
- discharge from hospital

Eligibility
Key inclusion criteria
Adult patients, greater than or equal to 60 years old
elective, non-cardiac, surgery
major surgery expected to last for greater than or equal to 2 hours, with expected greater than or equal to 2 days as hospital in-patient
ASA 3 or 4
receiving a general anaesthesia, with or without a regional anaesthesia technique
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previously enrolled in study

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Using our pilot study data, to test baseline and supplemented ScO2 versus a primary outcome of MAE using repeated measures ANOVA, we estimate that 400 patients are required with significance of 0.01, to detect a 0.20 effect size, with a power of 0.99.

T-tests, Mann-Whitney U tests, and Fisher's exact tests, as appropriate, will be used to compare pre-operative patient characteristics to the dichotomous primary outcome (presence or absence of MAE) and secondary outcome (number of days of post-operative delirium).
ScO2 measurements will be averaged from both hemispheres prior to analysis. Baseline and supplemented ScO2 measurements will be compared against each outcome using repeated measures ANOVA. Post hoc univariate analysis will be performed with a Bonferroni correction for multiple pairwise comparisons. Change in ScO2 from baseline to supplemented (?ScO2) will be compared against each outcome using a 2-sample t-test or Mann-Whitney U test, as appropriate.
Significant pre- and intra-operative variables in a bivariate analysis for each of the primary and secondary outcome will be entered into a logistic regression model, and reported as odds ratio with 95% CI. Receiver operating characteristic will be performed for both baseline and supplemented ScO2 values against outcomes, and reported as area under the curve (AUC) with 95% CI. Statistical significance will be determined by two-tailed analysis, p < 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/01/2017
Actual
23/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
128
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6052 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 6053 0
Macquarie University Hospital - Macquarie Park
Recruitment postcode(s) [1] 13502 0
2109 - Macquarie University
Recruitment postcode(s) [2] 13501 0
2170 - Casula

Funding & Sponsors
Funding source category [1] 293967 0
Hospital
Name [1] 293967 0
Department of Anaesthesia, Liverpool Hospital
Country [1] 293967 0
Australia
Primary sponsor type
Hospital
Name
Liverpool Hospital
Address
Elizabeth Street
NSW Liverpool 2170
Country
Australia
Secondary sponsor category [1] 292781 0
None
Name [1] 292781 0
Address [1] 292781 0
Country [1] 292781 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295382 0
South West Sydney HREC
Ethics committee address [1] 295382 0
‘Research and Ethics Office’
Locked Bag 7103
LIVERPOOL BC NSW 1871
Ethics committee country [1] 295382 0
Australia
Date submitted for ethics approval [1] 295382 0
29/07/2016
Approval date [1] 295382 0
01/12/2016
Ethics approval number [1] 295382 0

Summary
Brief summary
There is a biologically plausible mechanism to explain why pre-operative cerebral tissue oxygen saturation (ScO2) can be a surrogate measure of underlying cardiopulmonary function. ScO2, as measured by near-infrared spectroscopy, represents a dynamic balance between oxygen delivery and extraction by cerebral tissue. When not physically active, there is a stable rate of cerebral oxygen extraction. When ScO2 is measured in patients who are resting, breathing room air, and without the influence of medications, the ScO2 value is primarily determined by the effectiveness of oxygen delivery by the cardiopulmonary system. Low pre-operative ScO2 is thus an indication of poor cardiopulmonary reserve.

This has been demonstrated in studies correlating pre-operative ScO2 values to existing measures of cardiopulmonary function, including left ventricular ejection fraction, pulmonary artery catheter cardiac output, and with cardiopulmonary exercise testing. Subsequent studies in cardiac surgery patients have found that low pre-operative ScO2 is associated with increased risk of death, delirium, and major adverse events.

We performed a pilot study which showed that low pre-operative ScO2 below 68% is similarly observed to increase the risk of mortality or major morbidity in major non-cardiac surgery. To confirm these pilot study results, we intend to perform a prospective, double blinded, multicentre observational study on the predictive role of low pre-operative cerebral tissue saturation and major adverse outcomes in elderly, high risk patients undergoing major elective non-cardiac surgery.

Aims
The primary outcome of this study is to determine if low resting pre-operative ScO2, measured in room air and with oxygen supplementation, is associated with mortality or major morbidity. The secondary outcome of this study is to determine if low resting pre-operative ScO2 is associated with increased risk of post-operative delirium.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67062 0
Dr Alwin Chuan
Address 67062 0
Department of Anaesthesia
Level 1, New Clinical Building
Liverpool Hospital
Elizabeth Street
Liverpool NSW 2170
Country 67062 0
Australia
Phone 67062 0
+61 407743668
Fax 67062 0
Email 67062 0
a.chuan@unsw.edu.au
Contact person for public queries
Name 67063 0
Alwin Chuan
Address 67063 0
Department of Anaesthesia
Level 1, New Clinical Building
Liverpool Hospital
Elizabeth Street
Liverpool NSW 2170
Country 67063 0
Australia
Phone 67063 0
+61 2 9828 3173
Fax 67063 0
Email 67063 0
a.chuan@unsw.edu.au
Contact person for scientific queries
Name 67064 0
Alwin Chuan
Address 67064 0
Department of Anaesthesia
Level 1, New Clinical Building
Liverpool Hospital
Elizabeth Street
Liverpool NSW 2170
Country 67064 0
Australia
Phone 67064 0
+61 407743668
Fax 67064 0
Email 67064 0
a.chuan@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD to be reviewed by ethics committee regards validity against original approval decision


What supporting documents are/will be available?

No Supporting Document Provided



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.