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Trial registered on ANZCTR


Registration number
ACTRN12623001198617
Ethics application status
Approved
Date submitted
9/10/2023
Date registered
20/11/2023
Date last updated
20/11/2023
Date data sharing statement initially provided
20/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of wavelet semblance analysis for determining the lower limit of cerebral autoregulation in a non-cardiac surgery population
Scientific title
Evaluation of wavelet semblance analysis for determining the lower limit of cerebral autoregulation in a non-cardiac surgery population
Secondary ID [1] 303200 0
Nil known
Universal Trial Number (UTN)
U1111-1263-9335
Trial acronym
WAVELET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intraoperative hypotension 320330 0
Condition category
Condition code
Anaesthesiology 318247 318247 0 0
Anaesthetics
Cardiovascular 328587 328587 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 328588 328588 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
Robust research has established a clear association between perioperative complications and intraoperative hypotension (IOH) with even minor degrees of hypotension, below a mean arterial blood pressure (MAP) of 65 mmHg, associated with significant morbidity and mortality.

Using the brain as the index organ and raw data generated from intraoperative monitoring with near-infrared spectroscopy (NIRS) combined with invasive blood pressure, this study aims to evaluate wavelet semblance analysis in a surgical population. In doing so, aim to also determine the previously undefined lower limit of cerebral autoregulation (LLA) of patients under general anaesthetic in the non-cardiac surgery setting.

As an observational study, this study will not alter clinical care. All patients will be managed with general anaesthesia performed by, or under the supervision of, a consultant anaesthetist. Qualified medical or nursing personnel will complete a detailed, standardised data collection form to ensure patient eligibility, identify other potential confounders, document basic demographic and medical data, and assign formal surgical and anaesthetic risk scores.

Qualified clinical staff will also deliver neuropsychiatric/cognitive assessments pre operatively including the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and the Institute of cognitive neurology (INECO) Frontal screening assessments. Concurrent mood state assessments will be performed using the Depression, Anxiety and Stress Scale (DASS-21). Individual changes from baseline will be assessed on day 3 post-operatively for evidence of cognitive impairment. Cognitive decline will be defined as a deterioration of greater than a 20% reduction from baseline in at least two cognitive components assessed.

Routine clinical parameters will be captured iintraoperatively ncluding basic respiratory (pulse oximetry saturation, inspired and end- tidal oxygen, carbon dioxide, and anaesthetic agent), and cardiac (electrocardiogram, heart rate) measures. These will be downloaded using data capture software. Information regarding management (e.g. drug administration, procedural details including type/duration of surgery and any anaesthetic issues) will also be recorded. An arterial line will be placed by the treating anaesthetist for routine invasive blood pressure monitoring and blood sampling.

Additional study specific data will be recorded intraoperatively through routine clinical methods including:
- Arterial blood gas measurements performed every 30 minutes to assess acid/base status and arterial partial pressures of oxygen and carbon dioxide, both of which can affect cerebrovascular reactivity.
- NIRS monitoring, which is often used routinely during many types of surgery in The Prince Charles Hospital (TPCH and
- Electroencephalography will be performed (as recommended for routine clinical practice) with a Bispectral Index (BIS) sensor over the forehead, which also will be placed pre-induction.
- Prior to induction, an appropriately sized ClearSight Cuff (or AIQ Cuff) (Edwards Lifesciences, CA, USA) will also be placed on the patient’s non-operative second, third, or fourth digit at the middle phalanx. The ClearSight Heart Reference Sensor will be zeroed and placed at the patient’s phlebostatic axis. This cuff will be connected to an Edwards Haemodynamic monitoring platform (EV1000 or HemoSphere), and all Cardiac Output parameters will be transferred to a research-specific laptop.

Blood samples will be collected at baseline (day 0) and at 6, 24 and 48 hoursdaily for 3 days post-op. Sample collection will follow standard phlebotomy procedures and be performed by either the treating anaesthetist or a trained phlebotomist. At all timepoints, two EDTA tubes (3 mL, lavender-top) and one serum separator tube or SST (5 mL, gold-top) will be drawn for study samples. Tubes will be filled by vacuum and gently inverted 6 - 8 times to ensure adequate mixing. All samples will be immediately transferred to the Queensland Pathology laboratories at TPCH and PAH for processing. Processing will include testing for creatinine, troponin I and BNP. One of the EDTA tubes will be centrifuged (for 15 min at 4 degrees Celcius, 3000 x g) and stored at -80 degree Celcius until study completion, when it will be processed for biomarkers for neurological injury.
Intervention code [1] 319500 0
Not applicable
Comparator / control treatment
No control group, observational
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326228 0
Autoregulation analysis will be undertaken by comparing rSO2 and arterial blood pressure, using both wavelet semblance analysis and the COx index (Pearson correlation of 5 minute epochs rSO2 vs MAP). The primary outcome measures will be the proportion of patients where the LLA inflexion point can be determined (i.e. with a detectable LLA) reported as a percentage of the total cases. A 50% success is predicted to be the limit of feasibility and it the typical value achieved in the literature
Timepoint [1] 326228 0
Following enrollment and data collection for the final patient in the study
Secondary outcome [1] 390616 0
Data from near-infrared spectroscopy (NIRS) and invasive blood pressure monitor will determine the magnitude of intraoperative hypotension calculated as time MAP< LLA (time x mmHg)
Timepoint [1] 390616 0
Continuously measured during surgery, with signal processing taking place once data captured post surgery.
Secondary outcome [2] 390617 0
Occurrence of any perioperative complications assessed from patient surgical records
Timepoint [2] 390617 0
Assessed up until 48 hours post operatively
Secondary outcome [3] 428124 0
Organ hypoperfusin/injury as assessed by clinical correlates:
Brain injury: EEG suppression,
Kidney injury: serum creatinine, and
Myocardial injury: Troponin.
Timepoint [3] 428124 0
Assessed up until 48 hours post operatively
Secondary outcome [4] 428125 0
EEG suppression
Timepoint [4] 428125 0
Assessed up until 48 hours post operatively
Secondary outcome [5] 428126 0
Kidney injury, assessed by a clinically significant rise in serum creatinine
Timepoint [5] 428126 0
Assessed up until 48 hours post operatively
Secondary outcome [6] 428127 0
Myocardial injury as determined by a clinically significant in cardiac Troponin I from baseline
Timepoint [6] 428127 0
Assessed up until 48 hours post operatively

Eligibility
Key inclusion criteria
Capacity and willingness to consent; age >= 18; undergoing elective non-cardiac (including major general, orthopaedic, vascular, plastic, thoracic or urological) surgery; requiring general anaesthesia; and, are planned to have a clinically-indicated or ‘routine’ intra-arterial line inserted. Major orthopaedic surgery includes shoulder, hip or knee reconstruction or replacement.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systolic blood pressure > 180 mmHg; or, have any relative or absolute contraindication to NIRS placement (e.g., dermatitis, allergy to sticking tape).

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Primary analysis: Autoregulation analysis will be undertaken by comparing rSO2 and arterial blood pressure, using both wavelet semblance analysis and the COx index (Pearson correlation of 5 minute epochs rSO2 vs MAP). The primary outcome measures will be the proportion of patients where the LLA inflexion point can be determined (i.e. with a detectable LLA) reported as a percentage of the total cases. A 50% success is predicted to be the limit of feasibility and it the typical value achieved in the literature. 100 cases gives power to discriminate +/- 10% and thus should identify if we achieve >60% which would be a clinically significant and meaningful improvement over previous methods. Where the LLA is detected, the value in mmHg will be described by mean +/- standard deviation as well as range. Such summary statistics for this patient population, especially range will indicate the level of blood pressure below which cerebral blood flow (and hence other organ blood flow) may be too low.

Secondary analysis: Extensive secondary analysis will be undertaken of this rich dataset to optimise the autoregulation analysis technique. The magnitude of IOH will be calculated as the mean difference between LLA and MAP (where MAP < LLA, in mmHg) multiplied by the time.

Associations with clinical correlates (organ hypoperfusion/injury: EEG suppression, kidney injury (creatinine), and myocardial injury [Troponin I]) of IOH will be analysed using multivariate modelling.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
8/01/2024
Actual
Date of last participant enrolment
Anticipated
30/06/2024
Actual
Date of last data collection
Anticipated
30/06/2024
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 18440 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 18441 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 32548 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 32549 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 307601 0
Hospital
Name [1] 307601 0
The Prince Charles Hospital Foundation
Country [1] 307601 0
Australia
Primary sponsor type
Hospital
Name
The Prince Charles Hospital
Address
The Prince Charles Hospital, 627 Rode Road, Chermside, Qld, Aus 4032
Country
Australia
Secondary sponsor category [1] 308294 0
None
Name [1] 308294 0
Address [1] 308294 0
Country [1] 308294 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307655 0
The Prince Charles Hospital Human Research Ethics Committee (EC00168)
Ethics committee address [1] 307655 0
Ethics committee country [1] 307655 0
Australia
Date submitted for ethics approval [1] 307655 0
08/11/2018
Approval date [1] 307655 0
19/12/2018
Ethics approval number [1] 307655 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108026 0
Dr Jonathon Fanning
Address 108026 0
Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Chermside, Qld 4032
Country 108026 0
Australia
Phone 108026 0
+61 410 408 777
Fax 108026 0
Email 108026 0
jonathon.fanning@health.qld.gov.au
Contact person for public queries
Name 108027 0
Jonathon Fanning
Address 108027 0
Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Chermside, Qld 4032
Country 108027 0
Australia
Phone 108027 0
+61 7 3139 6880
Fax 108027 0
Email 108027 0
TPCH-CCRG@health.qld.gov.au
Contact person for scientific queries
Name 108028 0
Jonathon Fanning
Address 108028 0
Critical Care Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Chermside, Qld 403
Country 108028 0
Australia
Phone 108028 0
+61 7 3139 6880
Fax 108028 0
Email 108028 0
TPCH-CCRG@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data will be available upon appropriate request
When will data be available (start and end dates)?
Data will be available following publication in a peer reviewed journal; for a maximum of 5 years.
Available to whom?
To researchers who provide a methodologically sound proposal, on a case-by-case basis at the discretion of Principle Investigator.
Available for what types of analyses?
Only to achieve the aims in the approved proposal or for IPD meta-analyses
How or where can data be obtained?
Email to the PI: Dr Jonathan Fanning, TPCH-CCRG@health.qld.gov.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10268Ethical approval    381242-(Uploaded-09-10-2023-16-11-17)-Study-related document.pdf



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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