Is Enoxaparin Associated With a Higher Risk of Persistent Wound Drainage Than Aspirin? A Secondary Analysis of Data From the CRISTAL Randomized Trial.

BACKGROUND: Owing to its association with prosthetic joint infection, persistent wound drainage has become an important clinical entity after THA or TKA. The association between venous thromboembolism (VTE) prophylaxis and persistent wound drainage has not been extensively reported before but has potentially important clinical implications. QUESTIONS/PURPOSES: (1) Is the type of VTE prophylaxis (enoxaparin or aspirin) used after hip arthroplasty or knee arthroplasty associated with a higher risk of persistent wound drainage? (2) In patients who experience persistent wound drainage, is the type of VTE prophylaxis associated with a longer time taken to achieve a dry wound? (3) Is type of VTE prophylaxis associated with a higher risk of joint-related reoperation within 6 months? METHODS: This was a secondary analysis of data from an earlier cluster-randomized trial conducted through the Australian Orthopaedic Association National Joint Replacement Registry; data were drawn from two participating hospitals from that study. According to the trial's allocation sequence, the two participating hospitals were randomized to administer aspirin (100 mg daily) or enoxaparin (40 mg daily) as VTE prophylaxis to all patients undergoing hip arthroplasty for 35 days after the procedure and for all patients undergoing knee arthroplasty for 14 days afterwards. Crossover to the alternate prophylaxis group occurred after the patient enrollment target had been met for the first arm. Between April 2019 and December 2020, 1339 of 1679 eligible patients were included in this study; 82% (707 of 861) of eligible patients were allocated to the enoxaparin group and 77% (632 of 818) of eligible patients we allocated to the aspirin group. The mean age in both groups was 67 ± 10 years and the mean BMI was 32 ± 7 kg/m 2 . There was a higher proportion of male patients (43% [302 of 707] versus 36% [227 of 632]; p = 0.01), hip arthroplasties (36% [254 of 707] versus 29% [182 of 632]; p = 0.006), and patients receiving subcuticular closure (62% [441 of 707] versus 33% [208 of 631]; p < 0.001) in the enoxaparin group than in the aspirin group. Patients were monitored for wound drainage on each postoperative day until discharge, and this was recorded in the medical record once per day. Assessors were not blinded to the type of prophylaxis each patient received. Persistent wound drainage was defined as any wound drainage beyond Postoperative Day 3. For patients who experienced persistent wound drainage, the time taken to achieve a dry wound was defined as the number of days beyond Postoperative Day 3 for the wound to become dry. Logistic regression was used to determine whether the prophylaxis type was associated with persistent wound drainage. For patients with persistent wound drainage, the median time of drainage was compared between groups using the Kruskal-Wallis test. The number of patients undergoing a joint-related reoperation within 6 months was identified through data linkage to the Australian Orthopaedic Association National Joint Replacement Registry and electronic record review, and was compared using a Fisher exact test. RESULTS: We found no difference between the enoxaparin and aspirin groups in terms of the percentage of patients who had persistent wound drainage (9% [65 of 707] versus 8% [49 of 632], odds ratio 1.2 [95% confidence interval 0.8 to 1.8]; p = 0.40). For patients receiving subcuticular closure, after controlling for other potentially confounding variables, including age, sex, BMI, preoperative anticoagulant use, and type of arthroplasty, enoxaparin was associated with a higher risk of persistent wound drainage than aspirin (OR 3.6 [95% CI 1.5 to 10.6]; p = 0.009). For patients receiving a skin staple closure, after controlling for the same variables above, we found enoxaparin was not associated with a higher risk of persistent wound drainage (OR 1.1 [95% CI 0.7 to 1.9]; p = 0.66). For patients who experienced persistent wound drainage patients (114: 65 in the enoxaparin group and 49 in the aspirin group), there was no difference in the median (interquartile range) time taken to achieve a dry wound (enoxaparin: 1 day [IQR 1 to 2 days], aspirin: 1 day [IQR 1 to 3 days]; p = 0.22). There was no difference in the risk of joint-related reoperation within 6 months between enoxaparin (2.4% [17 of 707]) and aspirin (2.2% [14 of 632], OR 1.1 [95% CI 0.5 to 2.4]; p = 0.86). CONCLUSION: Enoxaparin was not associated with an increased risk of persistent wound drainage compared with aspirin for all patients included in this study. Enoxaparin may be associated with a higher risk of drainage for patients receiving subcuticular closure. However, this finding should be interpreted cautiously, given the small sample size in this analysis. The duration of drainage was short regardless of the prophylaxis used, and enoxaparin was not associated with an increased risk of joint-related reoperation. These findings should not deter clinicians from using enoxaparin for VTE prophylaxis after hip or knee arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparative effectiveness of aspirin for symptomatic venous thromboembolism prophylaxis in patients undergoing total joint arthroplasty, a cohort study.

BACKGROUND: This study compares the symptomatic 90-day venous thromboembolism (VTE) rates in patients receiving aspirin to patients receiving low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), after total hip (THA) and total knee arthroplasty (TKA). METHODS: Data were collected from a multi-centre cohort study, including demographics, confounders and prophylaxis type (aspirin alone, LMWH alone, aspirin and LMWH, and DOACs). The primary outcome was symptomatic 90-day VTE. Secondary outcomes were major bleeding, joint related reoperation and mortality within 90 days. Data were analysed using logistic regression, the Student's t and Fisher's exact tests (unadjusted) and multivariable regression (adjusted). RESULTS: There were 1867 eligible patients; 365 (20%) received aspirin alone, 762 (41%) LMWH alone, 482 (26%) LMWH and aspirin and 170 (9%) DOAC. The 90-day VTE rate was 2.7%; lowest in the aspirin group (1.6%), compared to 3.6% for LMWH, 2.3% for LMWH and aspirin and 2.4% for DOACs. After adjusted analysis, predictors of VTE were prophylaxis duration < 14 days (OR = 6.7, 95% CI 3.5-13.1, p < 0.001) and history of previous VTE (OR = 2.4, 95% CI 1.1-5.8, p = 0.05). There were no significant differences in the primary or secondary outcomes between prophylaxis groups. CONCLUSIONS: Aspirin may be suitable for VTE prophylaxis following THA and TKA. The comparatively low unadjusted 90-day VTE rate in the aspirin group may have been due to selective use in lower-risk patients. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, trial number NCT01899443 (15/07/2013).

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

Importance: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Objective: To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA. Design, Setting, and Participants: Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021. Interventions: Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation. Main Outcomes and Measures: The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group. Results: Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group. Conclusions and Relevance: Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis. Trial Registration: ANZCTR Identifier: ACTRN12618001879257.

The operative outcomes of displaced medial-end clavicle fractures.

BACKGROUND: Nonoperative treatment of displaced medial clavicle fractures often leads to poor functional outcomes and painful nonunions. This study investigates the functional outcomes of patients undergoing operative fixation of these fractures. METHODS: We investigated 27 patients undergoing operative fixation of a medial clavicle fracture; 24 had an acute, displaced fracture and 3 had fixation for nonunions. Preoperative radiographs or computed tomography scans were obtained, and data collected included age, sex, mechanism of injury, and fixation method. Follow-up included physical examination and radiographs for assessment of union; Disabilities of the Arm, Shoulder, and Hand scores at 12 months; and the recording of complications. RESULTS: The median age was 37 years (interquartile range, 17-47 years). There were 26 male patients and one female patient included, with 7 physeal injuries and 20 adult injuries. The most common mechanism of fracture was vehicular accident (n = 15). Three patients had operations for nonunions and 2 for a periprosthetic fracture medial to an existing plate. The fracture was fixed with plate and screws in 19 cases and with transosseous sutures in 8 cases. The median Disabilities of the Arm, Shoulder, and Hand score at 12 months was 0.4 (interquartile range, 0-5.0), with a union rate of 100% at 12 months. All patients had full shoulder range of motion at final follow-up and were able to return to preinjury occupational activities. There were no significant complications. CONCLUSION: Operative fixation of displaced medial clavicle fractures results in anatomic reconstruction and excellent functional outcomes, even in the setting of fixation performed for symptomatic nonunion. Early intervention can minimize the risk of painful nonunion.

Evaluating the cost of robotic-assisted total and unicompartmental knee arthroplasty.

As uptake of robotic-assisted arthroplasty increases there is a need for economic evaluation of the implementation and ongoing costs associated with robotic surgery. The aims of this study were to describe the in-hospital cost of robotic-assisted total knee arthroplasty (RA-TKA) and robotic-assisted unicompartmental knee arthroplasty (RA-UKA) and determine the influence of patient characteristics and surgical outcomes on cost. This prospective cohort study included adult patients (≥ 18 years) undergoing primary unilateral RA-TKA and RA-UKA, at a tertiary hospital in Sydney between April 2017 and June 2021. Patient characteristics, surgical outcomes, and in-hospital cost variables were extracted from hospital medical records. Differences between outcomes for RA-TKA and RA-UKA were compared using independent sample t-tests. Logistic regression was performed to determine drivers of cost. Of the 308 robotic-assisted procedures, 247 were RA-TKA and 61 were RA-UKA. Surgical time, time in the operating room, and length of stay were significantly shorter in RA-UKA (p < 0.001); whereas RA-TKA patients were older (p = 0.002) and more likely to be discharged to in-patient rehabilitation (p = 0.009). Total in-hospital cost was significantly higher for RA-TKA cases (AU$18580.02 vs $13275.38; p < 0.001). Robotic system and maintenance cost per case was AU$3867.00 for TKA and AU$5008.77 for UKA. Patients born overseas and lower volume robotic surgeons were significantly associated with higher total cost of RA-UKA. Increasing age and male gender were significantly associated with higher total cost of RA-TKA. Total cost was significantly higher for RA-TKA than RA-UKA. Robotic system costs for RA-UKA are inflated by the software cost relative to the volume of cases compared with RA-TKA. Cost is an important consideration when evaluating long term benefits of robotic-assisted knee arthroplasty in future studies to provide evidence for the economic sustainability of this practice.

Post-discharge patient-reported non-adherence to aspirin compared to enoxaparin for venous thromboembolism prophylaxis after hip or knee arthroplasty.

BACKGROUND: Aspirin and enoxaparin are commonly used for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). The purpose of this study was to compare non-adherence after discharge to aspirin or enoxaparin following THA or TKA. METHODS: A subset of participants in the CRISTAL study were selected for participation. Additional inclusion criteria were no preoperative anticoagulant use and discharge from hospital before the prophylaxis period ended. The first four consecutive patients from each arm at each participating hospital were planned to be recruited (planned sample size n = 248). A patient-reported adherence questionnaire was completed by telephone at 36-41 days after THA and at 15-20 days after TKA. The primary outcome was non-adherence. Secondary outcomes were number of missed doses and the reasons for non-adherence. RESULTS: There were 178 participants included from 15 sites, less than planned explained by early stopping of trial recruitment. There was no significant between-group difference in patient-reported non-adherence: 24% (17/71) for aspirin, 30% (32/107) for enoxaparin, odds ratio = 1.4 (95% CI 0.7-2.9). The mean number of missed doses was 2.5 for aspirin and 3.4 for enoxaparin (mean difference = 0.9 doses, 95% CI -1.2 to 3.1). For aspirin, the most commonly reported reason for non-adherence was forgotten doses and for enoxaparin it was clinician-recommended change. CONCLUSIONS: Rates of non-adherence and the number of missing doses were similar for patients regardless of drug prescribed. The most common reasons for non-adherence were unrelated to the mode of administration.

Effect of Aspirin vs Enoxaparin on 90-Day Mortality in Patients Undergoing Hip or Knee Arthroplasty: A Secondary Analysis of the CRISTAL Cluster Randomized Trial.

Importance: Ischemic heart disease remains the leading cause of mortality following hip and knee arthroplasty. Due to its antiplatelet and cardioprotective properties, aspirin has been proposed as an agent that could reduce mortality when used as venous thromboembolism (VTE) prophylaxis following these procedures. Objective: To compare aspirin with enoxaparin in reducing 90-day mortality for patients undergoing hip or knee arthroplasty procedures. Design, Setting, and Participants: This study was a planned secondary analysis of the CRISTAL cluster randomized, crossover, registry-nested trial performed across 31 participating hospitals in Australia between April 20, 2019, and December 18, 2020. The aim of the CRISTAL trial was to determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE following hip or knee arthroplasty. The primary study restricted the analysis to patients undergoing total hip or knee arthroplasty for a diagnosis of osteoarthritis only. This study includes all adult patients (aged ≥18 years) undergoing any hip or knee arthroplasty procedure at participating sites during the course of the trial. Data were analyzed from June 1 to September 6, 2021. Interventions: Hospitals were randomized to administer all patients oral aspirin (100 mg daily) or subcutaneous enoxaparin (40 mg daily) for 35 days after hip arthroplasty and 14 days after knee arthroplasty procedures. Main Outcomes and Measures: The primary outcome was mortality within 90 days. The between-group difference in mortality was estimated using cluster summary methods. Results: A total of 23 458 patients from 31 hospitals were included, with 14 156 patients allocated to aspirin (median [IQR] age, 69 [62-77] years; 7984 [56.4%] female) and 9302 patients allocated to enoxaparin (median [IQR] age, 70 [62-77] years; 5277 [56.7%] female). The mortality rate within 90 days of surgery was 1.67% in the aspirin group and 1.53% in the enoxaparin group (estimated difference, 0.04%; 95% CI, -0.05%-0.42%). For the subgroup of 21 148 patients with a nonfracture diagnosis, the mortality rate was 0.49% in the aspirin group and 0.41% in the enoxaparin group (estimated difference, 0.05%; 95% CI, -0.67% to 0.76%). Conclusions and Relevance: In this secondary analysis of a cluster randomized trial comparing aspirin with enoxaparin following hip or knee arthroplasty, there was no significant between-group difference in mortality within 90 days when either drug was used for VTE prophylaxis. Trial Registration: http://anzctr.org.au Identifier: ACTRN12618001879257.

Implementation and audit of 'Fast-Track Surgery' in gynaecological oncology surgery.

BACKGROUND: Fast-track surgery is a multidisciplinary approach to surgery that results in faster recovery from surgery and decreased length of stay (LOS). AIMS: The aims of this study were as follows: (i) to report on the processes required for the introduction of fast-track surgery to a gynaecological oncology unit and (ii) to report the results of a clinical audit conducted after the protocol's implementation. METHODS: A fast-track protocol, specific to our unit, was developed after a series of multidisciplinary meetings. The protocol, agreed upon by those involved in the care of women in our unit, was then introduced into clinical practice. An audit was conducted of all women undergoing laparotomy, with known or suspected malignancy. Information on LOS, complication and readmission rates was collected. Descriptive statistics and Poisson regression were used for statistical analysis. RESULTS: The developed protocol involved a multidisciplinary approach to pre-, intra- and postoperative care. The audit included 104 consecutive women over a 6-month period, who were followed for 6 weeks postoperatively. The median LOS was 4 days. The readmission rate was 7% and the complication rate was 19% (1% intraoperative, 4% major and 14% minor). Multivariate analysis revealed that increased duration of surgery and increasing age were predictors of longer LOS. CONCLUSION: The development of a fast-track protocol is achievable in a gynaecological oncology unit, with input from a multidisciplinary team. Effective implementation of the protocol can result in a short LOS, with acceptable complication and readmission rates when applied non-selectively to gynaecological oncology patients.

Aspirin versus enoxaparin for the initial prevention of venous thromboembolism following elective arthroplasty of the hip or knee: A systematic review and meta-analysis.

BACKGROUND: Aspirin is perceived to be non-inferior to enoxaparin, a low-molecular-weight heparin, for the prevention of venous thromboembolism (VTE) following elective arthroplasty of the hip or knee and is recommended in clinical guidelines internationally. Previous systematic reviews of aspirin as VTE prophylaxis have been limited by the inclusion of heterogenous studies where aspirin is commenced after the initial high-risk postoperative period. The purpose of this systematic review and meta-analysis was to compare the efficacy and associated harms of aspirin and enoxaparin when used as VTE prophylaxis in the initial postoperative period following elective arthroplasty of the hip or knee. We sought to: (1) to compare the use of aspirin versus enoxaparin following elective joint replacement of the hip or knee on the primary outcomes of incidence of VTE and mortality up to 3 months postoperatively and (2) assess the efficacy of aspirin with respect to secondary outcomes such as major or minor bleeding events. We hypothesised that aspirin would have equivalent efficacy for the prevention of VTE when used as initial prophylactic agent, without increasing harm from bleeding events. PATIENTS AND METHODS: We searched Pubmed, Embase, Medline and Cochrane Central for randomized controlled trials reporting the primary outcomes of VTE incidence and mortality. Secondary outcomes included major (compromise of organ, limb or muscle function requiring unplanned re-operation) and minor bleeding events (wound ooze, minor bleed, infection). Included trials underwent a risk of bias and quality of evidence assessment using the GRADE criteria. RESULTS: Four trials involving 1507 participants who underwent elective lower limb arthroplasty were included. We did not detect a significant difference in overall VTE rates when comparing aspirin versus enoxaparin (RR, 0.84; 95% CI: 0.41 to 1.75; p=0.65). Mortality was reported by one study and no events were recorded. There were no significant differences in the rates of all major (RR, 0.84; 95% CI: 0.08 to 9.16) or minor (RR, 0.77; 95% CI: 0.34 to 1.72) bleeding events between the aspirin and enoxaparin groups. Included trials demonstrated a significant risk of bias, and Low to Very Low quality of evidence for primary outcomes, and Moderate to Very Low for secondary outcomes. CONCLUSION: There is currently a lack of high quality randomised controlled trials supporting the use of aspirin as VTE chemoprophylaxis in the initial postoperative period for both total hip and total knee arthroplasty. The results of this meta-analysis provide cautious endorsement for the position that aspirin is likely a safe alternative to enoxaparin for TKA patients as part of a multimodal enhanced recovery protocol, but care is advised for THA patients owing to a lack of data from trials. Current evidence from randomized controlled trials is generally of low quality, and does not estimate critical event data for VTE incidence or mortality, as well as major and minor bleeding events with sufficient certainty. PROSPERO Registration CRD42018110784. LEVEL OF EVIDENCE: II, systematic review.

3D printed models can guide safe halo pin placement in patients with diastrophic dysplasia.

PURPOSE: To trial the use of three-dimensional (3D) printed skull models to guide safe pin placement in two patients with diastrophic dysplasia (DTD) requiring prolonged pre-fusion halo-gravity traction (HGT). METHODS: Two sisters aged 8 (ML) and 4 (BL) with DTD were planned for staged fusion for progressive kyphoscoliosis. Both sisters were admitted for pre-fusion HGT. Models of their skulls were generated from computer tomography (CT) scans using Mimics Innovation Suite and printed on a Guider II in polylactic acid. The 3D models were cut axially proximal to the skull equator, in-line where pins are usually inserted, allowing identification of the thickest skull portion to guide pin placement. RESULTS: Eight pins were inserted into each patient's skull. Postoperative CT scans demonstrated adequate pin position. Pre-traction Cobb angles were 122° and 128° for ML and BL, improving to 83° and 86° following traction. Duration of HGT was 182 and 238 days for ML and BL. Prior to fusion, both patients returned to theatre twice for exchange of loose pins and there was one incidence of pin site infection. Surgery was performed via a posterior instrumented fusion. Postoperatively, both patients remained in their halos for 3 months. One pin in BL was removed for loosening. Both patients achieved fusion union by 9 months. CONCLUSION: 3D models of the skull can be a useful tool to guide safe pin placement in patients with skeletal dysplasias, who require prolonged pre-fusion HGT for severe deformity correction.

CRISTAL (a cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study): statistical analysis plan.

BACKGROUND: This a priori statistical analysis plan describes the analysis for CRISTAL. METHODS: CRISTAL (cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome. The clusters comprised hospitals performing > 250 HA and/or KA procedures per annum, whereby all adults (> 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85-150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm. The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months. The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes. CONCLUSIONS: This paper provides a detailed statistical analysis plan for CRISTAL. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12618001879257 . Registered on 19/11/2018.

CRISTAL: protocol for a cluster randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study.

INTRODUCTION: Venous thromboembolism (VTE) is a serious complication following hip arthroplasty (HA) and knee arthroplasty (KA). This study aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic VTE following HA and KA. METHODS AND ANALYSIS: This is a cluster randomised, crossover, non-inferiority, trial nested within the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The clusters will consist of Australian hospitals performing at least 250 HA and/or KA procedures per annum. All adult patients undergoing HA or KA will be included. The intervention will be aspirin, orally, 85-150 mg daily. The comparator will be LMWH (enoxaparin) 40 mg, subcutaneously, daily. Both drugs will commence within 24 hours postoperatively and continue for 35 days after HA and 14 days after KA. Each hospital will be randomised to commence with aspirin or LMWH and then crossover to the alternative treatment after meeting the recruitment target. Data will be collected through the AOANJRR via patient-reported surveys. The primary outcome is symptomatic VTE within 90 days post surgery, verified by AOANJRR staff. The primary analysis will include only patients undergoing elective primary total hip arthroplasty and total knee arthroplasty for osteoarthritis. Secondary outcomes will include symptomatic VTE for all HA and KA (including partial and revision) within 90 days, readmission, reoperation, major bleeding and death within 90 days and reoperation, death and patient-reported pain, function and health status at 6 months. If aspirin is found to be inferior, a cost-effectiveness analysis will be conducted. The study will aim to recruit 15 562 patients from 31 hospitals. ETHICS AND DISSEMINATION: Ethics approval has been granted. Trial results will be submitted for publication. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001879257, pre-results) and is endorsed by the Australia and New Zealand Musculoskeletal Clinical Trials Network.