A clinical trial to determine if aspirin is as effective and safe as low molecular weight heparin in preventing lung and leg clots after total hip or knee replacement surgery
A cluster randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis and safety in hip or knee arthroplasty, a registry nested study
University of New South Wales
15,562 participants
Apr 15, 2019
Interventional
Conditions
Summary
Background Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are the two most costly procedures performed in Australia. Venous thromboembolism (VTE) – pulmonary embolism (PE) or deep venous thrombosis (DVT) remain serious complications of THA and TKA and there is current uncertainty regarding which drugs should be used as chemoprophylaxis. Low molecular weight heparin (LMWH) is the most commonly recommended and used, but many surgeons use aspirin as it is a safe, efficacious, easy to administer and a low cost alternative. Study Aim This study aims to compare LMWH and aspirin in VTE prevention in patients undergoing THA or TKA at hospitals contributing data to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). It is hypothesised that aspirin will be non-inferior to LMWH in preventing symptomatic 90-day VTE. Study Design and Intervention The study will use the AOANJRR to perform a registry-nested, cluster randomised crossover trial. The intervention will be aspirin given orally (once daily, 85-150mg) and the comparator will be LMWH (enoxaparin, 40mg subcutaneously), both given for 35 days after THA and for 14 days after TKA. Study Outcomes The primary outcome is verified symptomatic VTE within 90 days in patients undergoing primary THA or TKA for osteoarthritis. Secondary outcomes will include a cost-effectiveness analysis, efficacy for all THA or TKA (revision, primary, performed for any diagnosis) and non-VTE complications between the two groups (including wound ooze as a sub-study). Study Timeline Thirty-one institutions have commenced recruiting patients in 2019. Recruitment of patients for the CRISTAL trial will take at least 12 months for each treatment arm, yielding approximately 15,500 patients. It is estimated the study will take a further 12 months to complete for data analysis and manuscript preparation. This would provide a conservative estimate of 4 years for study completion.
Eligibility
Inclusion Criteria1
- Adults (age 18 and older) receiving elective primary or revision TKA or THA
Exclusion Criteria2
- Departments that perform less than 250 THA or TKA proecedures per year
- The following patients will be excluded from the primary analysis: patients receiving partial joint replacements, revision surgery, non-osteoarthritis diagnosis, use of warfarin/NOAC/dual antiplatelet therapy pre-operatively
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
Aspirin at a dose of 85-150mg, administered once daily, orally, to all patients undergoing primary or revision THA or TKA as VTE chemoprophylaxis. The dose used is based on availability, some hospitals or surgeons have a dose of 100mg more readily available, whilst others have 150mg more readily available. Patients undergoing THA will receive this for 35 days and patients undergoing TKA will receive this for 14 days, commencing within 24 hours postoperatively. This timing window of within 24 hours is used based on the surgeon's discretion as to when the procedure is performed (e.g. in the morning, evening) and how much bleeding is perceived to have occurred. The exact duration is based on the investigators' discretion. Adherence will be monitored by a patient questionnaire performed at 90 days postoperatively. This dose and duration of aspirin was chosen as it is recommended by the recent United Kingdom National Institute for Health and Care Excellence (NICE) guidelines (2018). The Crossover trial refers to the crossover of hospitals from one treatment arm to the second (e.g. one hospital will prescribe all patients aspirin only for a 9 month period and then low molecular weight heparin only for a second 9 month period), rather than patients crossing over from one treatment to the second. Therefore, there will be no 'wash-out' period for patients.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12618001879257