Should intermittent pneumatic compression devices be standard therapy for the prevention of venous thromboembolic events in major surgery? Protocol for a randomised clinical trial (IMPOSTERS)

Abstract

Introduction

Venous thromboembolism (VTE) is a recognised postsurgical risk. Current prevention methods involve low molecular weight heparin (LMWH), graduated compression stockings (GCS), and intermittent pneumatic compression devices (IPCDs). Australian guidelines, commonly adopted by surgeons, recommend LMWH with GCS and/or IPCDs. IPCDs pose clinical risks, increase care burden, are poorly tolerated, and are costly single-use plastic items. Utilising only LMWH and GCS, without IPCDs, could be more practical, patient-friendly, and cost-effective, with added environmental benefits.

Methods

This is a multicentre, prospective, two-arm randomised controlled non-inferiority trial at five New South Wales (NSW) hospitals, in Australia. We propose to randomise 4130 participants in a 1:1 ratio between arm A: LMWH+GCS+IPCDs (n=2065) or arm B: LMWH+GCS (n=2065). The primary outcome of interest is symptomatic VTE (deep vein thrombosis/pulmonary embolism) identified at the day 30 phone follow-up (FU), confirmed by ultrasound or imaging. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation. Secondary outcomes are quality of life at baseline, days 30 and 90 FU using the 5-level European Quality of Life Score, compliance and adverse events with IPCDs, GCS, and LMWH, as well as healthcare costs (from the perspective of the patient and the hospital), and all-cause mortality. The trial has 90% power to detect a 2% non-inferiority margin to detect a reduction rate of VTE from 4% to 2%.

Ethics and dissemination

This study has been approved by the Hunter New England Human Research Ethics Committee (2022/ETH02276) protocol V.10, 13 July 2023. Study findings will be presented at local and national conferences and in scientific research journals.

Trial registration number

ANZCTR12622001527752

STRENGTHS AND LIMITATIONS OF THIS STUDY

• This will be the largest trial looking at the impact of intermittent pneumatic compression devices on the prevention of venous thromboembolism. It is a multisite, randomised, controlled study across New South Wales, Australia.

• This will be the first randomised trial for venous thromboembolism prophylaxis with a health economic cost-effective analysis incorporated.

• Patients, surgeon, and nursing staff are not blinded to the allocation introducing potential bias, although outcome assessors are blinded.

Background and rationale

Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE),¹ represents one of the most feared postoperative complications following surgery. This can result in short-term and long-term morbidity or death, yet it is also one of the most common preventable causes of death when optimal thromboprophylaxis is employed.

Over the past 30 years, intermittent pneumatic compression devices (IPCDs) have been widely marketed as a therapeutic medical device. It is theorised IPCDs influence the stasis and flow of blood in the lower leg when worn. This is achieved by inflating a sleeve placed circumferentially on the lower or upper part of the leg,² which actively empties the deep veins of the limb in a predetermined cycle of pressure, producing a column of blood that travels proximally thereby preventing stasis.³ Recommendations for VTE prophylaxis in surgical patients are risk-based and include a combination of low molecular weight heparin (LMWH), graduated compression stockings (GCS), and/or intermittent pneumatic compression devices (IPCDs).¹ The optimal combination of VTE prophylaxis in major surgery is unknown. Currently, there is no evidence in major surgery to support the use of IPCDs as an adjunct to LMWH and GCSs during and postsurgery.⁴ Despite this, their use has become commonplace for patients recovering from surgery.⁵

Since the 1960s, thromboembolism guidelines have been repeatedly revised, with new evidence emerging mainly for anticoagulation therapies rather than mechanical prophylaxis.^{1 6–14} Recommendations from VTE guidelines (ASH, NICE, RACS, and ACCP)^{1 6–14} all state that for effective VTE prophylaxis of surgical patients, it is important to treat patients according to their individual VTE risk, their clinical condition, the bleeding risk, and the appropriateness of the prophylaxis for the individual patient.¹ Local Australian guidelines based on the Royal Australian College of Surgeons (RACS) recommend LMWH with GCS and/or IPCDs, in major surgery.^{1 6} Our team’s recent survey of surgeons VTE prophylaxis practices⁵ revealed a notable discrepancy between clinicians’ usage of all three modalities and the lack of support for this approach in current evidence-based guidelines. While the guidelines are supposed to be evidence based, the current pool of evidence is outdated or not good quality. This underscores a clear gap between existing evidence and its practical implementation in clinical settings.

Systematic reviews analysing randomised controlled trials have explored diverse combinations of pharmacological and mechanical prophylaxis to inform guideline recommendations.^15–19 There remains an ongoing conflict as to what is the best and most appropriate prophylaxis for patients admitted to hospital having major surgery. Combinations of modalities may be more effective than single interventions. However, studies included in these systematic reviews have been too small to draw strong conclusions on the use of all three forms of prophylaxis (LMWH+GCS+IPCDs) for patients having major surgery.

A frequently cited Cochrane review by Kakkos et al ¹⁸ concluded that combining IPCDs with pharmacological prophylaxis showed no significant difference in preventing PE and DVT compared with using IPCDs alone or anticoagulation alone. The study highlighted the need for further research due to moderate-quality evidence and methodological ambiguities.

Early comparisons of VTE prevention (usually using unfractionated or LMWH) with a placebo or no intervention were undertaken decades ago, when surgical techniques, anaesthesia, and postoperative management were very different.⁴ Enhanced recovery after surgery programmes have changed many aspects of perioperative care for patients undergoing major surgery. Older trials are no longer clinically relevant or applicable. Early mobilisation and ambulation as a strategy to prevent DVT is founded on the fact that immobilised patients are at a high risk for DVT and PE.^{20 21} High-risk surgeries have pathways that emphasise early ambulation and mobilisation as not only a strategy for VTE prevention but also to improve respiratory and gut function. Using IPCDs can be limiting for the patient trying to get out of bed, walk to the toilet, shower and physiotherapy; in a practical sense, patients are tethered to the bed or chair.

IPCD safety, cost, and value to the public health service

While case reports are considered a lower form of evidence, if prepared carefully and interpreted with appropriate caution, case reports can have a valuable part to play in both the advancement of medical knowledge and the pursuit of education. There have been a few case reports of compartment syndrome,²² case reports of peroneal nerve palsy,²³ and a case report of PE,²⁴ all in association with IPCD use.^{25 26} The totality of these reports potentially calls into question the safety profile of IPCDs if their use could be a factor in the higher incidence of thromboembolic complications in surgical patients. A case report, by Siddiqui et al,²⁴ describes a patient who had multiple risk factors for deep venous thrombosis but was asymptomatic, and IPCDs were suspected to have been involved in the dislodgment of an already established thrombus. The report suggests an increased incidence of thromboembolic complications in patients who had IPCDs on their legs; however, it is difficult to establish a causal relationship between these devices and the aetiology of deep venous thrombosis.

Our internal hospital audit found that IPCDs are frequently used in surgery but not worn or even turned on postsurgery. It could be postulated that the application of all three treatments is more about the litigious nature of healthcare in the current climate. A study at two university-affiliated level one trauma centres found IPCDs to be functioning properly in only 19% of trauma patients.^{26 27} In another study of gynaecologic oncology patients, 52% of IPCDs were functioning improperly and 25% of patients experienced some discomfort, inconvenience, or problems with external pneumatic compression.²⁸ Redness, itching, or discomfort was cited by 26% of patients, and patients removed IPCDs 11% of the time when nurses left the room.²⁸ Concerns about a possible link between IPCDs and increased fall risk was raised by a 2005 report of 40 falls by the Pennsylvania Patient Safety Reporting System,^{29 30} IPCDs accounted for 16 of 3562 hospital falls according to Boelig and colleagues.³⁰ The most important perceived barriers to IPCD compliance according to patient surveys was that the devices ‘prevented walking or getting up’ (47%), ‘were tethering or tangling’ (25%), and ‘woke the patient from sleep’ (15%).²⁷

Local costing obtained from the John Hunter Hospital, a ~800 bed tertiary referral hospital in regional New South Wales (NSW), Australia, suggests that the procurement cost for IPCDs could be in excess of $150 000 per year.³¹ At a time when health budgets are under unprecedented strain, this represents a potentially avoidable cost on the public health system. For this reason, an economic evaluation will be conducted in parallel to the RCT outlined below.

All of this highlights the need to determine whether IPCDs are beneficial for patients undergoing major surgery, particularly when adequate pharmacological prophylaxis is employed. Given the lack of evidence to suggest that both mechanical forms of VTE prophylaxis are required when adequate pharmacological prophylaxis is given, we believe that a non-inferiority trial is required to compare LMWH and GCS with LMWH, GCS, and IPCDs (current standard but more costly and with potential for higher non-VTE-associated risk).

Trial objectives and purpose

The main objective is to investigate the non-inferiority and potential superiority of LMWH and GCS (less intervention and potential lower cost) compared with LMWH, GCS, and IPCDs (most frequently used combination) for VTE prophylaxis in patients undergoing major surgery. Secondary aims are to:

1. Examine the safety, tolerability, and practical implementation of IPCDs, considering reported complications.

2. Investigate factors affecting IPCD compliance, such as patient discomfort and fall risks.

3. Conduct an economic evaluation to assess the cost-effectiveness of incorporating IPCDs into standard prophylaxis.

4. Address the observed discrepancy between clinical practices and evidence-based guidelines for VTE prophylaxis in major surgery.

Methods

Trial design

This study will be a two-armed prospective, randomised controlled non-inferiority clinical trial in patients undergoing major surgery at five hospitals throughout NSW in three different local health districts. The RCT will assess non-inferiority and potential superiority of the combination of LMWH, GCS, and IPCDs (arm A, n=2065) to the combination of LMWH, GCS (arm B, n=2065).

Study setting

This is a multicentre site study based at five hospitals and within three local health districts (LHDs) in NSW, Australia. The five hospital encompasses both metropolitan and rural communities.

Inclusion criteria

For the purposes of this study, age and major surgery are defined by the following:

1. Aged≥18 years of age.

2. Major surgery as per classification by the Royal Australasian College of Surgeons (RACS).^{1 32}

3. Planned hospital admission ≥24 postsurgery for medical reasons.

4. Moderate or high risk of VTE based on NSW risk assessment form (online supplementary A).

Exclusion criteria

Patients will be excluded if they meet the criteria outlined in the VTE guidelines:¹

• Individuals lack the capacity to provide consent to participate in the study.

• Are not expected to be ambulant within 24 hours.

• Have contraindications to LMWH.

• Have contraindications to GCS or IPCDs.

• Have had previous heparin-induced thrombocytopenia/thrombosis.

• Are undergoing orthopaedic surgery.

• Have active, clinically significant bleeding (class 2 and above) that is, volume loss of 15% to over 40% of total blood volume.

• Have documented congenital or acquired bleeding tendency/disorders.

• Have had recent intracranial haemorrhage or recent (less than 3 months prior to randomisation) brain spinal, or ophthalmologic surgery.

• Have active peptic ulcer or treatment of same in the last 3 months.

• Have severe liver disease (liver cirrhosis).³³

• Have current thrombocytopenia, for example, platelets<70 (150–400 (10⁹/L)

• Have renal impairment glomerular filtration rate<30 and or creatinine level above 2.0 mg/dL (180 µmol/L) in a well-hydrated participant.

• Are pregnant and/or breastfeeding women.

• Have evidence of leg ischaemia caused by peripheral vascular disease (previously documented or on clinical assessment).

• Have a clinical sign of VTE and/or history of VTE-PE, DVT.

• Have pre-existing indications for the need of heparins (including LMWH). These are people at a high risk of getting clots, to reduce their chances of developing serious conditions such as strokes and heart attacks that is, atrial fibrillation, pulmonary hypertension, cardiomyopathy, ischaemic stroke, certain congenital heart disorders, artificial valve replacement.

• Are COVID+ve or have had COVID-19 in the past 10 days.³⁴

Recruitment and consent

Research nurses will assess potential participants’' eligibility by reviewing referral for admission documents for those scheduled for major surgery. The Hunter Research Ethics Committee (HREC) approved the ‘opt-out’ Participant Information Statement and Consent Form. This will be provided through email, mail, or during perioperative clinic appointments to eligible individuals, as per inclusion criteria. This consent model presumes agreement unless explicitly stated otherwise. Participants can watch a concise (<5 min) video in the perioperative clinic, addressing the study’s nature, purpose, procedures, expected duration, and potential risks/benefits. For improved comprehension, the video and ‘opt out’ consent form can be sent via REDCap^{35 36} before clinic appointments or follow-up calls.

Patient and public involvement statement

A former surgical patient consumer identified via the Hunter Medical and Research Institute (HMRI) was invited to serve as a collaborator. They participated in consumer training by HMRI. Their input informed the design of the study, the grant application, the development of the ‘opt out’ consent form, patient diary, and selection of relevant outcomes to collect.

Intervention and control group

Preoperative and operative periods

All participants will undergo a standardised preoperative preparation for surgery which will include routine ECG, chest X-ray, a VTE risk assessment score, and blood tests. Blood tests will include a full blood count, urea, creatinine, and electrolytes. Demographic (age, sex, ethnicity, height, and weight) and clinical data will be recorded. This is current standard pre-operative care.

Participants in both arms will receive LMWH immediately after surgery. GCS will be applied to all participants 1–2 hours preoperatively, as per current VTE guidelines.¹⁰ Participants in arm A will also have IPCD applied in surgery.

Postoperative period (day 0 to discharge)

All participants are encouraged to start mobilising on the first day postsurgery, including sitting up based on their clinical condition. In arm A, participants will remove GCS only during bathing and reapply them at the bedside. For IPCDs, they will be removed during mobilisation and bathing. In arm B, participants will remove GCS and to be reapplied at the bedside. Compliance will be recorded in a research patient diary, either electronically through REDCap^{35 36} or on paper. LMWH compliance will be assessed via medication chart review by a Research Nurse.

Before discharge, participants will receive written guidance on preventing blood clots, including exercises and will be advised to consult their general practitioner (GP) or hospital if VTE symptoms occur. A letter will be sent to the participant’s GP regarding their trial participation.

Primary outcome measure

Symptomatic VTE (DVT/PE) identified up to day 30, confirmed by ultrasound (USS) or imaging. This is a dichotomous outcome indicating the presence of any of the following symptoms.

Deep vein thrombosis (DVT) symptoms³⁷

• Swelling in one leg (usually the calf or thigh).

• Pain or tenderness in the affected leg.

• Warmth and redness over the affected area.

• Swollen veins that may be visible.

Pulmonary embolism (PE) symptoms³⁸

• Shortness of breath.

• Chest pain that may become worse when breathing deeply, coughing, or even swallowing.

• Rapid heart rate.

• Cough that may produce bloody or blood-streaked sputum.

• Sweating.

• Feeling lightheaded or dizzy.

(It is important to note that not everyone with VTE experiences symptoms, and in some cases, the condition may be asymptomatic.)

Secondary outcome measures

• Symptomatic VTE (DVT/PE) identified at day 90 follow-up, confirmed by USS or imaging.

• Quality of Life–5-level European Quality of Life Score (EQ-5D-5L) (online supplementary B): The EQ-5D-5L is a brief survey of health status covering five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.³⁹

• Sleep disturbance: assessed with the PROMMIS-SF (online supplementary C).⁴⁰

• Functional Health: assessed using the WHODAS-12 (online supplementary D). The WHO International Classification of Functioning, Disability and Health (ICF) including the six domains: cognition, mobility, self-care, getting along, life activities, and participation. This will be used to capture potential inpatient and outpatient functional disturbances because of IPCDs.⁴¹

• Patient experience: assessed using the Inpatient PREM question set available from NSW Agency for Clinical Innovation (Inpatient PREM questions (nsw.gov.au)) to capture patient’s perception of their experience during their inpatient stay.⁴²

• Compliance with IPCDs, GCS, and LMWH (patient diary) (online supplementary E).

• Overall mortality and Clavien-Dindo classification will also be collected.

  • The Clavien-Dindo Classification allows for a standardised and objective assessment of surgical complications, facilitating communication among healthcare professionals and researchers. It helps in comparing outcomes across different studies and serves as a valuable tool for quality improvement initiatives in the field of surgery. ⁴³

• Health care resource use (Costs and potential cost effectiveness of the interventions). This involves assessing both the direct monetary expenses associated with the intervention and its overall impact on health outcomes including direct expenses, healthcare utilization, and patient-related costs. Additionally, a cost-effectiveness analysis considers the intervention's impact on health outcomes, quality of life, and long-term economic sustainability.

• IPCD related complications (bilateral peroneal nerve palsies, lower leg compartment syndrome, neurovascular compression).^22–26

• Bleeding complications- Any anticoagulant can pose a risk of bleeding complications, defined as surgical site bleeding, internal bleeding (requiring blood transfusion or surgery), gastrointestinal bleeding (may manifest as black, tarry stools or vomiting blood) and intracranial haemorrhage.

• LOS (Length of Stay in hospital).

• Days alive and out of hospital.

• Hospital and Emergency admissions related to VTE.

Sample size

The sample size is based on data from the GAPS trial (UK)⁴⁴ on surgical inpatients with similar risk. The day 30 VTE rates in this trial were 1.4% and 1.7% for the control and intervention groups. We have assumed a slightly higher rate of 2.5% to adjust for the fact that the cohort will be at a slightly higher VTE risk via inclusion criteria. We have performed a binational (Australia and New Zealand) survey of surgeons that undertake high risk abdominal surgery and found that 100% of them would not use IPCDs if they provided less than a 2% reduction in VTE rates. We have therefore chosen a conservative non-inferiority margin (NIM) of 1.5%.

To determine the sample size and corresponding frequentist operating characteristics, we simulated data for both stages of the trial (interim and final). We considered two scenarios: (1) when the true proportions equal 2.5% (to assess power to declare non-inferiority and (2) when the proportion in the intervention group was unacceptably higher than the control group (4.5% vs 2.5%). The decision threshold to stop the trial for futility at the interim analysis was based on the posterior predicted probability of declaring non-inferiority at the end of the trial (trial being stopped for futility if this was 27.5% or lower). The decision threshold to declare non-inferiority at the final stage was based on the posterior probability that the difference was less than the NIM (non-inferiority declared if this probability exceeded a threshold of 90%). A final stage sample size of 1856 per group enables the study to correctly declare non-inferiority with 90% probability, and correctly declare futility at the interim analysis with 80% probability. To account for a conservative loss to follow-up of 10% 4130 patients are required, which is n=2065 per arm. The rate of incorrectly declaring non-inferiority (at the final stage) was 1% and incorrectly stopping the trial early (at the interim analysis) was 3%.

Randomisation

After eligibility assessment, participants will be randomly assigned to either control (LMWH+GCS+IPCD) or treatment (LMWH+GCS) with a 1:1 ratio using permuted blocks of 4 stratified by the site/facility of surgery. Stratification by site has been chosen, to minimise confounders between variations in postoperative protocols at different hospital sites. Randomisation will be done via REDCap.^{35 36} Randomisation will occur on the day of surgery for expedited patients or when the patient has been admitted for elective surgery.

Blinding

It is not feasible to blind either the participants, surgeons, or nurses to treatment allocation because the presence of the IPCDs is clearly identifiable. If an USS is required, it will be completed by a trained sonographer who will be blinded to treatment allocation and who has not previously been involved in the care of the participant. The importance of blinding will be explained to participants, and they will be asked to not inform the sonographer. In addition, those carrying out the 30-day and 90-day calls will be blinded to the allocation of the patient they are calling to avoid any potential ascertainment bias.

Data collection

At the preoperative review, baseline data are routinely gathered, encompassing demographic details and baseline health and risk assessment metrics (NSW Health VTE risk assessment tool and ASA). Secondary outcome measures are evaluated at 30 days and 3 months. These encompass, patient-centred measures (health-related quality of life via the EQ-5D-5L questionnaire,³⁹ sleep questionnaire (PROMMIS),⁴⁰ a functional health questionnaire and measure of global disability (WHODAS),⁴¹ life impact metric ‘days alive and out of hospital’), and complications using the Clavien-Dindo classification. Economic evaluation indicators will be collected, including healthcare resource utilisation, incorporating intensive care and hospital length of stays, along with representations to healthcare facilities. Participants GP’s will also be contacted to identify potential postdischarge complications in addition to the patient contact points for follow-up data.

Data management

REDCap^{35 36} is a secure, web-based software platform designed to support data capture for research studies. It offers an easy-to-use interface for validated data entry, tracks data manipulation through audit trails, facilitates automated export processes for smooth data retrieval into common statistical packages, and provides methods for seamlessly integrating and interacting with external data sources. Data will be analysed and reported in a deidentified and grouped format by the Clinical Research Design and Statistics team at HMRI using data sourced from the REDCap database.

COVID-19

The aspect of a recent COVID-19 infection is difficult and does represent a higher than normal risk of VTE postoperatively. Given the constant updating of surgical guidelines surrounding this scenario and the complex logistics of surgery, we believe that including these patients would reduce generalisability. As an example of the changing landscape surrounding COVID, the 3 months deferral of elective surgery stated when we started, the application process has since been decreased to 2 weeks depending on the triage category.³⁴ All ‘deferred’ elective patients with recent COVID-19 will be recruited; it is expected that only a handful of patients needing emergency surgery with recent COVID will be excluded.

Statistical analysis

Primary analysis

The primary analysis will involve all eligible participants who were randomised to receive an intervention, analysed according to their assigned intervention group. The occurrence of VTE will be assessed on day 30 postrandomisation. A Bayesian framework will be employed, utilising a binomial likelihood model with a beta (1:1) prior distribution to estimate the posterior distribution for the difference in VTE proportions between the intervention groups. Non-inferiority will be declared if the posterior probability of the difference being less than the prespecified NIM exceeds 95%. For handling missing data, we will implement imputation strategies outlined in a Statistical Analysis Plan.

Secondary outcomes

Analysis of secondary outcomes will adhere to the intention-to-treat principle within a Bayesian inferential framework. Continuous outcomes will be analysed using linear mixed models with repeated measures to account for within-subject correlation over time. Count outcomes will be addressed using either Poisson or negative binomial regression models, depending on the dispersion of the data. For dichotomous outcomes, especially those measured at multiple time points, we will employ generalised linear mixed models with random intercepts at the subject level. Additionally, an ordinal logistic regression mixed model will be utilised to compare groups based on the Modified Rankin Score.

Interim analysis

An interim analysis is planned when 50% of the projected recruitment is achieved. This analysis will estimate the posterior predictive probability of declaring non-inferiority at the end of the trial. A decision rule for futility will be applied: if this probability is less than 35%, the trial may be halted due to potential safety concerns or lack of efficacy in removing the intervention. This decision will be based on a careful consideration of both efficacy and safety data available at the time of the interim analysis.

Trial audit

The trial will be audited by an independent assessor from the HREC to ensure Good Clinical Practice in compliance with applicable laws and regulations. The study will be performed in accordance with the NHMRC Statement on Ethical Conduct in Research Involving Humans.

Monitoring

The NSW Trial management group (TMG) will be responsible for the day-to-day management of the trial in NSW. The role of the TMG will be to monitor all aspects of the conduct and progress of the trial, ensure that the protocol is adhered to and take appropriate action to safeguard participants and the quality of the trial itself.

Data Monitoring Committee (DMC)

Data analyses will be supplied in confidence to the independent DMC, which will be asked to give advice on whether the accumulated data and safety from the trial, together with the results from other relevant research, justifies the continuing recruitment of further participants.

The DMC may consider recommending the discontinuation of the trial if the recruitment rate or data quality are unacceptable or if any issues are identified which may compromise participant safety. The trial will also stop early if the interim analyses show differences between treatments that were deemed to be convincing to the clinical community.

Safety reporting

All potential serious adverse events will be reported immediately to the Principal Investigator (PI) who will report to the approving Human Research Ethics Committee (HREC) within 72 hours. Adverse events will also be reported annually to the HREC and be reported and discussed in any publication that may result from this research.

Serious adverse event definition: any untoward and unexpected medical occurrence or effect that:⁴⁵

• Results in death

• Is life threatening

• Requires hospitalisation, or prolongation of existing inpatient’s hospitalisation

• Results in persistent or significant disability or incapacity

Stopping guidelines for the use of compression devices:

The use of compression devices will be ceased if:

1. There is suspicion of lower limb DVT. If USS excludes DVT, then compression devices will be restarted.

2. There is suspicion of PE. If clinical and radiological assessments exclude PE, then compression devices will be restarted.

3. A pressure ulcer develops, or there are any breaks in lower limb skin integrity, or lower limb ischaemia preventing the use of compression devices.

Temporary or permanent cessation of compression devices will be recorded, including when stopping was initiated (days postsurgery) and the length of time compression devices were not used.

Health resource use

The first phase of evaluating resource use will involve a trial-based economic evaluation. Assuming a non-inferior trial outcome, a cost minimisation analysis will be conducted comparing only the costs of each study arm. Healthcare resource use and patient-incurred costs will be identified, measured, valued, and compared. In-patient resource use will be directly extracted from hospital administrative databases. Out of hospital and patient out-of-pocket costs will be based on self-reported data collected via survey during the telephone follow-up and will be complemented by Medicare and Pharmaceutical data in Australia. Sensitivity and uncertainty analysis will examine the impact of variation in the costs and outcomes on the economic summary result. The analysis will be consistent with published guidelines. Finally, a detailed budget impact assessment will be derived to assess the potential generalisability of the results and translation of the economic analysis to other surgical sites and interventions.

Ethics and dissemination

This study will be conducted according to the Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) in compliance with applicable laws and regulations. The study will be performed in accordance with the NHMRC Statement on Ethical Conduct in Research Involving Humans (Commonwealth of Australia 2007), and the principles laid down by the World Medical Association in 2008. The Investigators shall comply with the protocol, except when a protocol deviation is required to eliminate an immediate hazard to a participant. This study has been approved by the Hunter New England Human Research Ethics Committee (2022/ETH02276). ‘Opt-out’ consent has been requested and granted by the Hunter New England Human Research Ethics Committee (2022/ETH02276) due to the potential for introducing recruitment bias into the study with an ‘opt-in’ process, limiting generalisability. Protocol amendments will be furnished to the ethics committee responsible for approval, and site authorisations for each LHD will be obtained. Every approved protocol amendment will be endorsed by the Chief Investigator (CI) and PIs at each site. All data is retained on the HMRI REDCap secured web-based software. Only investigators who have the two branched authentication passwords can access data and only for their site. No other access for this trial will be given. The study’s findings will be communicated locally to hospital teams and shared on a national scale through conferences and presentations. Additionally, results will be disseminated via publication in scientific journals. Deidentified and summarised outcomes will be provided to external parties on specific requests made to the CI.

Ethics statements

Patient consent for publication

Not applicable.