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Trial registered on ANZCTR


Registration number
ACTRN12623000814673
Ethics application status
Approved
Date submitted
6/07/2023
Date registered
28/07/2023
Date last updated
23/09/2024
Date data sharing statement initially provided
28/07/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The GLOW Trial: implementing Guidelines for hypothermia prevention with Local adaptation to keep periOperative patients Warm.
Scientific title
Implementing Guidelines for hypothermia prevention with Local
adaptation to keep periOperative patients Warm (the GLOW Trial): A stepped wedge cluster trial to evaluate the effectiveness of consensus-based perioperative hypothermia prevention recommendations.
Secondary ID [1] 309714 0
NHMRC Partnership Project ID: APP2015532
Universal Trial Number (UTN)
Trial acronym
The GLOW trial.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Perioperative hypothermia (defined as a body temperature less than 36°C related to undergoing surgery) 330103 0
Condition category
Condition code
Anaesthesiology 326989 326989 0 0
Other anaesthesiology
Surgery 327478 327478 0 0
Other surgery
Public Health 327479 327479 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention - implementation of perioperative hypothermia prevention principles and practice recommendations supported by internal and external facilitation.
During a 6-month implementation transition period, local adaptation and implementation of the principles and practice recommendations will commence. Each cluster (perioperative department) will be provided with internal and external facilitation support for implementation of perioperative hypothermia recommendations comprising of 1. Simple principles for perioperative hypothermia prevention; 2. Supporting detailed practice recommendations. The recommendations comprise of the three domains of hypothermia prevention: (1) monitoring temperature, (2) warming actively, (3) minimising exposure.
Examples of the practice recommendations include: (1) Monitoring Temperature - Actively monitoring temperature for all patients at all times; (2) Warm Actively - warm actively to keep temperature above 36°C; (3) Minimise Exposure - minimise exposure to cold at all stages of perioperative care.

Intervention - Implementation Strategy
The core components of the implementation strategy are 1. a team-based approach to implement the recommendations with local adaptation; 2. expert facilitation and structured support. Each cluster (perioperative department) will form a Site Implementation Team including registered nurses, anaesthetists and surgeons. Internal facilitation will be provided within each department by a Registered Nurse. External facilitation is provided by the research team. The Site Implementation Teams will adapt the recommendations, according to context, while working through an implementation process that is guided by the Knowledge-to-Action framework. External facilitators will support internal facilitators and the Site Implementation Teams to work through the implementation process and adapt the recommendations to context, using the Knowledge-to-Action framework. Facilitation will provide both practical and theoretical support. The Site Implementation Teams will be provided with (1) the simple principles and detailed practice recommendations, and (2) implementation materials based on the Knowledge-to-Action framework, including an implementation guide (designed specifically for this study), electronic repository of implementation information and tools. The implementation teams will facilitate the adoption of recommendations and choose implementation strategies based on local context and needs. Examples may include local audit and feedback, priority setting and workshops, small scale testing of practice change using Plan Do Study Act (PDSA) cycles.

Intervention duration: each cluster will be randomized to commence the implementation transition phase which is 6 months in duration. Site Implementation Teams meet at an initial one-day workshop at the commencement of the six-month phase, then weekly throughout the six months. Sites then switch to the Intervention period of data collection and remain in the Intervention period until the end of the trial, between 8 to 18 months.

Intervention fidelity - activity logs will be used to assess fidelity to the implementation strategy.
Intervention code [1] 326156 0
Behaviour
Comparator / control treatment
Control: during the Control period, clusters continue with normal care. This study uses a stepped-wedge cluster randomised design. Each site will act as it's own control. Each site will be subject to a variable control and intervention period, based on the randomized order (and a fixed six-month implementation period). To reduce data collection burden, while maintaining adequate statistical power, an incomplete design will be used. This means that the sites randomised to clusters 4 and 5 will commence their control period in months 4 and 7 respectively. Clusters 1 to 3 will commence their control period in month 1. Therefore, this means that sites randomised to cluster 1 will undergo a 3-month control step; sites randomised to cluster 2 will undergo a 6-month control step and sites randomised to clusters 3 to 5 will undergo a 9-month control step.
Control group
Active

Outcomes
Primary outcome [1] 334841 0
Co-primary effectiveness outcome: perioperative hypothermia (defined as a temperature less than 36°C) - assessed via health record review.
Timepoint [1] 334841 0
On arrival to Post Anaesthetic Care Unit (PACU).
Primary outcome [2] 339439 0
Co-primary implementation outcome: the extent of temperature monitoring and active warming - assessed via health record review.
Timepoint [2] 339439 0
Primary outcome [3] 339440 0
Co-primary implementation outcome: the extent of temperature monitoring and active warming - assessed via health record review.
Timepoint [3] 339440 0
Longitudinal analysis across all perioperative timepoints: (1) preoperatively - within hour prior to surgery and on induction (2) intraoperatively - from surgery start to surgery end (3) in PACU - from PACU admission until discharge from PACU.
Secondary outcome [1] 422222 0
Perioperative hypothermia (defined as a temperature less than 36°C) - assessed via health record review.
Timepoint [1] 422222 0
Within hour prior to surgery; on induction; Intraoperatively - from anaesthetic induction to end of surgery; during PACU admission (any temperature checks); on ready to discharge from PACU.
Secondary outcome [2] 422223 0
Length of hospital stay (in days), defined as days of separation and assessed via admitted hospital data records.
Timepoint [2] 422223 0
Length of stay from admission to discharge.
Secondary outcome [3] 422224 0
Post Anaesthetic Care Unit length of stay (in hours) assessed via health record.
Timepoint [3] 422224 0
Post Anaesthetic Care Unit discharge.
Secondary outcome [4] 422225 0
Blood product transfusions, assessed via health record.
Timepoint [4] 422225 0
From surgical start time to discharge post-surgery.
Secondary outcome [5] 422226 0
Surgical site infection, as assessed by health records and hospital reports.
Timepoint [5] 422226 0
On discharge from episode of care.
At 30 days post-surgery.
Secondary outcome [6] 422228 0
Surgical site infection, as assessed via Bluebelle self-report wound healing validated survey.
Timepoint [6] 422228 0
At 30 days post-discharge from surgery.
Secondary outcome [7] 422229 0
Patient-reported quality of life, as assessed via EQ-5D-DL
Timepoint [7] 422229 0
Baseline (preoperative - within 48hours prior to surgery)
At postoperative Day 2
At postoperative Day 30
Secondary outcome [8] 422230 0
Unplanned admissions, as assessed via hospital records, and as per Australian Commission for Safety and Quality in Health Care definition.
Timepoint [8] 422230 0
At 28 days post-discharge.
Secondary outcome [9] 422231 0
Indication for unplanned admissions, as assessed via hospital records, and as per Australian Commission for Safety and Quality in Health Care definition.
Timepoint [9] 422231 0
At 28 days post-discharge.
Secondary outcome [10] 422232 0
Cost-effectiveness of intervention, as assessed via Quality of Life measures (via EQ-5D-DL), estimated staff time spent on implementation activities (via activity logs), hospital bed days and admission costs (as determined from hospital records), and unplanned admissions (as determined from hospital records).
Timepoint [10] 422232 0
At end of trial.
Secondary outcome [11] 423349 0
Implementation context: assessed via survey using Organisational Readiness for Change tool.
Timepoint [11] 423349 0
During month 1 of six-month transition period
Secondary outcome [12] 424026 0
Implementation outcome: implementability of intervention assessed using a survey incorporating validated tools, using Likert scales, to assess intervention acceptability, feasibility and appropriateness (Weiner et al. 2017) and structured response options incorporating questions from the validated CAPGO questionnaire ( Brouwers et al.2009) adapted for use in the perioperative context.
Timepoint [12] 424026 0
During month 1 of six-month transition period, at end of transition period.
Secondary outcome [13] 424151 0
Implementation outcome: actual implementation strategy use assessed via activity logs.
Timepoint [13] 424151 0
At end of transition period.
Secondary outcome [14] 424152 0
Implementation outcome: actual adoption of practice recommendations assessed via structured survey, designed specifically for this study.
Timepoint [14] 424152 0
At end of transition period.
Secondary outcome [15] 424154 0
Implementation outcome: site implementation team experience via a study-specific survey incorporating questions using Kirkpatrick's levels of training evaluation (Kirkpatrick 2016).
Timepoint [15] 424154 0
During month 1 and at end of transition period.
Secondary outcome [16] 424456 0
Implementation outcome: site implementation team learning via a study-specific survey incorporating the validated Practicing Knowledge Translation too (Moore et al. 2018)
Timepoint [16] 424456 0
During month 1 of transition and end of transition period.
Secondary outcome [17] 424457 0
Implementation outcome: site implementation capacity assessed via via a study-specific survey incorporating the validated Implementation Climate Scale (Ehrhart et al 2021).
Timepoint [17] 424457 0
During month 1 of transition and end of transition period.

Eligibility
Key inclusion criteria
Patient participants: Adults aged 16yrs or older having undergone general or neuraxial, elective or emergency surgery at the hospital site during the site's control or intervention period will be eligible for inclusion. A random sample of patients undergoing elective surgery will be approached prior to surgery to participate in the collection of data for patient-reported outcomes (Quality of Life, self-reported wound healing) in addition to clinical outcomes collected for the main study.
Clinicians: For the implementation outcomes, clinicians will be included in implementation evaluation surveys if they have been involved in the Site Implementation Team (including registered or enrolled nurses, anaesthetic technicians, surgical and anaesthetic medical personnel). In addition, any clinician working in the perioperative department including registered or enrolled nurses, anaesthetic technicians, surgical and anaesthetic medical personnel) during the study period will be eligible to complete the surveys assessing Organisational Readiness for Implementation in addition to evaluation of the recommendations (feasibility, acceptability).
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient participants
Patients receiving planned therapeutic hypothermia or undergoing local anaesthesia only, or local anaesthesia with sedation only, or sedation only will be excluded. Patients who are transferred directly to the Intensive Care Unit from operating theatres and bypass the Post Anaesthetic Care Unit will be excluded from data collection. Patients who are who are undergoing cardiac or obstetric surgery, will be excluded from data collection.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Site randomisation to clusters 1 to 5 will occur only after all sites have been enrolled. Only Chief Investigators and the Project Coordinator will have access to the cluster intervention timings. Allocation concealment will be maintained until ~10 weeks prior to a cluster commencing implementation, to allow for employment of internal facilitators to commence and for Site Implementation Teams to be formed and prepared for implementation transition.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization of sites to treatment sequences will result in each site being randomized to receive the intervention at a different time. Sequence generation will be conducted by the Chief Investigator statistician. We will use a constrained randomization approach to account for facility size.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Other
Other design features
Stepped-wedge cluster randomised hybrid type II effectiveness-implementation study.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: As recommended by Curran et al. we have selected one co-primary aim in determining the required sample size: the clinical effectiveness outcome of perioperative hypothermia. The expected proportion of patients with perioperative hypothermia on PACU arrival at baseline is 0.274 (27%), based on a recent period prevalence study of five Australian hospitals. Minimum sample sizes were calculated based on the primary clinical outcome assuming unequal cluster sizes using a constrained randomisation approach. The use of constrained randomisation allows for site-specific sample sizes to represent a fixed proportion of their total surgical capacity, while aiming to minimise imbalance between the total sample sizes for Control and Intervention periods. For each month a site is in the Control or Intervention period, we will audit a random sample equal to 10% of monthly surgical cases, stratified according to duration of surgery. . Based on annual surgical numbers for participating sites, a 10% sample corresponds to 59 to 226 patients/site/month. To obtain at least 80% power, our proposed sampling strategy will detect a statistically significant and clinically relevant reduction from 0.274 (27%) in the Control period to 0.2 (20%) in the Intervention period. Calculations assume a 5% level of statistical significance, an expected intraclass correlation coefficient (ICC) of 0.1. Across the constrained subset of possible randomisations, the total sample size for Control and Intervention periods combined will be between 12,732 and 14,100. As over 280,000 patients will undergo surgery at the sites over the study duration, we do not anticipate any issues in reaching the required sample size. Additionally, data collection will be highly feasible given that most data points will be accessed via existing sources of routinely collected hospital-level data.

For the sample size, we have also considered the minimum detected increase in the primary implementation outcome (implementation of perioperative hypothermia prevention). Given the lack of data on the proposed outcome, we have used data on current adherence to perioperative temperature monitoring at all recommended timepoints. Assuming that 2.7% of patients currently receive perioperative temperature monitoring at all recommended timepoints, with remaining parameters unchanged, we will be able to detect an increase from 0.027 (2.7%) in the Control period to 0.1 (10%) in the Intervention period with 82% power.

For analysis of secondary outcomes (QoL; self-reported wound infection; satisfaction) including the economic evaluation, a randomly selected sub-sample of up to 1,500 patients will be directly recruited and prospectively followed-up (to allow for incomplete responses). This comprises an average of 300 directly recruited patients per site over the 27-month trial duration, for pragmatic purposes.

Data Analysis: The co-primary outcomes will be analysed using Generalised Linear Mixed Models (GLMM), assuming binary dependent variables. A random intercept will be defined for each site to account for clustering of observations under the stepped wedge design. Fixed effects will include intervention exposure (yes/no), calendar time to account for secular trends unrelated to the intervention (in months)21 and patient-level/surgery-level characteristics. The binary fixed effect for the intervention will estimate the expected within-site change in the co-primary outcomes associated with the intervention.

Associations between the dependent variable and fixed effects will be modelled using the logit link function. An identity link function will also be fitted as a comparison, to report risk differences. If the identity link function does not allow the model to converge, results for the logit link function will only be reported. Results for both unadjusted (except clustering) and adjusted analyses will be reported. Model parameters will be reported as estimated odds ratios (risk differences) with 95% confidence intervals.

Subgroup analyses for the co-primary outcomes will examine intervention effects by sex, surgical specialty, type of anaesthesia, duration of surgery, elective/emergency, American Society of Anesthesiologists’ classification I-V. A sensitivity analysis will also consider hypothermia defined at the following thresholds: less than 36°C; less than 35.5°C; less than 35°C.

Secondary outcomes will be similarly modelled based on the form of the dependent variable. Binary and count outcomes will be modelled using Binomial and Poisson GLMMs, respectively. Models for count outcomes will assume a common denominator of cases per 1,000 surgeries. Length of stay will be modelled using Cox proportional hazards regression. Analysis of survey and activity log data will be reported descriptively by study period.

Results for intention to treat (i.e., all data analysed for all sites as randomised) and per-protocol (i.e., data will be censored for sites if they withdraw from the trial protocol) will be reported. Missing data on primary and secondary outcomes is expected to be low. In the event of missing data on patient-level covariates, missingness will be investigated and if missing at random variables will be imputed using multiple imputation. Levels of missing data (if any) will be reported in planned research outputs.

Cost-effectiveness analysis: A within-trial cost-effectiveness analysis will compare costs and health outcomes of the evidence-based recommendations versus usual care from a health system perspective. The analysis will be conducted from the Australian health system perspective and the time horizon will be 30 days, consistent with the follow-up period of the trial. As such, discounting will not be required. Additional staff time involved with adoption will be estimated using activity logs completed by hospital staff and costed using mid-points of hospital salary ranges. Implementation costs including clinician engagement, and implementation activities will be prospectively recorded. Costs of equipment, materials and consumables, length of stay and readmissions will be retrospectively extracted from department budgets and hospital costing units.

The cost-effectiveness analysis will adopt QALYs as the measure of effectiveness. QALYs will be estimated using utility scores derived from the EQ-5D-5L questionnaire within the PRO subgroup across three time points. The EQ-5D-5L is the most widely used health utility tool internationally. QALYs will be derived by estimating the area under the curve using the methods described by Manca et al. Patients with only a baseline and no follow-up EQ-5D-5L questionnaires will be excluded from the cost-effectiveness analysis. For patients with one missing follow-up point, utility scores will be imputed using multiple imputation methods.

Results will be reported as incremental cost-effectiveness ratios (ICERs) and Net Monetary Benefits using a Willingness to Pay threshold of $50,000 per QALY. To assess uncertainty in the cost-effectiveness outcomes, a non-parametric probabilistic sensitivity analysis will be performed using bootstrapping of individual cost and QALY estimates with 10,000 replications. This will generate 10,000 ICERs which will be plotted on a cost-effectiveness plane and used to estimate mean and 95% confidence intervals for Net Monetary Benefit, along with cost-effectiveness acceptability curves. Where appropriate, one-way sensitivity analyses and scenario analyses will be conducted to assess the impact of key drivers on the cost-effectiveness outcome.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/09/2023
Actual
27/11/2023
Date of last participant enrolment
Anticipated
27/02/2026
Actual
Date of last data collection
Anticipated
29/03/2026
Actual
Sample size
Target
12732
Accrual to date
3407
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 24784 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 24785 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 24786 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [4] 24787 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [5] 24788 0
Ipswich Hospital - Ipswich
Recruitment postcode(s) [1] 40423 0
4029 - Herston
Recruitment postcode(s) [2] 40424 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 40425 0
4575 - Birtinya
Recruitment postcode(s) [4] 40426 0
4101 - South Brisbane
Recruitment postcode(s) [5] 40427 0
4305 - Ipswich

Funding & Sponsors
Funding source category [1] 313908 0
Government body
Name [1] 313908 0
National Health and Medical Research Council (NHMRC)
Country [1] 313908 0
Australia
Primary sponsor type
University
Name
University of the Sunshine Coast
Address
Victoria Park Rd,
Kelvin Grove,
QLD 4059
Country
Australia
Secondary sponsor category [1] 315767 0
None
Name [1] 315767 0
Address [1] 315767 0
Country [1] 315767 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313054 0
Metro North B Human Research Ethics Committee
Ethics committee address [1] 313054 0
Ethics committee country [1] 313054 0
Australia
Date submitted for ethics approval [1] 313054 0
28/02/2023
Approval date [1] 313054 0
28/03/2023
Ethics approval number [1] 313054 0
HREC/2023/MNHB/94571

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

Contacts
Principal investigator
Name 126830 0
A/Prof Judy Munday
Address 126830 0
University of the Sunshine Coast, 1 Moreton Parade, Petrie, QLD 4502
Country 126830 0
Australia
Phone 126830 0
+61 7 5456 3124
Fax 126830 0
Email 126830 0
jmunday1@usc.edu.au
Contact person for public queries
Name 126831 0
Judy Munday
Address 126831 0
University of the Sunshine Coast, 1 Moreton Parade, Petrie, QLD 4502
Country 126831 0
Australia
Phone 126831 0
+61 7 5456 3124
Fax 126831 0
Email 126831 0
jmunday1@usc.edu.au
Contact person for scientific queries
Name 126832 0
Judy Munday
Address 126832 0
University of the Sunshine Coast, 1 Moreton Parade, Petrie QLD 4502
Country 126832 0
Australia
Phone 126832 0
+61 7 5456 3124
Fax 126832 0
Email 126832 0
jmunday1@usc.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
Due to requirements of ethical approval.


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.