PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT): a randomised pragmatic trial protocol comparing aspirin versus low-molecular-weight heparin for blood clot prevention in orthopaedic trauma patients.

Introduction: Patients who sustain orthopaedic trauma are at an increased risk of venous thromboembolism (VTE), including fatal pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin (LMWH) for VTE prophylaxis in orthopaedic trauma patients. However, emerging literature in total joint arthroplasty patients suggests the potential clinical benefits of VTE prophylaxis with aspirin. The primary aim of this trial is to compare aspirin with LMWH as a thromboprophylaxis in fracture patients.
Methods and Analysis: PREVENT CLOT is a multicentre, randomised, pragmatic trial that aims to enrol 12 200 adult patients admitted to 1 of 21 participating centres with an operative extremity fracture, or any pelvis or acetabular fracture. The primary outcome is all-cause mortality. We will evaluate non-inferiority by testing whether the intention-to-treat difference in the probability of dying within 90 days of randomisation between aspirin and LMWH is less than our non-inferiority margin of 0.75%. Secondary efficacy outcomes include cause-specific mortality, non-fatal PE and deep vein thrombosis. Safety outcomes include bleeding complications, wound complications and deep surgical site infections.
Ethics and Dissemination: The PREVENT CLOT trial has been approved by the ethics board at the coordinating centre (Johns Hopkins Bloomberg School of Public Health) and all participating sites. Recruitment began in April 2017 and will continue through 2021. As both study medications are currently in clinical use for VTE prophylaxis for orthopaedic trauma patients, the findings of this trial can be easily adopted into clinical practice. The results of this large, patient-centred pragmatic trial will help guide treatment choices to prevent VTE in fracture patients.
Trial Registration Number: NCT02984384.
Competing Interests: Competing interests: CDM has received grant funding as PI from Merck and receives consulting income from AstraZeneca, Bayer Pharmaceuticals, Janssen/J&J, Merck and Pfizer. ERH is/was the primary investigator of contracts from The Patient-Centred Outcomes Research Institute (PCORI) entitled 'Preventing Venous Thromboembolism: Empowering Patients and Enabling Patient-Centred Care via Health Information Technology' (CE-12-11-4489) and 'Preventing Venous Thromboembolism (VTE): Engaging Patients to Reduce Preventable Harm from Missed/Refused Doses of VTE Prophylaxis' (DI-1603-34596); is the primary investigator of a grant from the Agency for Healthcare Research and Quality (AHRQ) (1R01HS024547) entitled 'Individualised Performance Feedback on Venous Thromboembolism Prevention Practice,' and is a co-investigator on a grant from the NIH/NHLBI (R21HL129028) entitled 'Analysis of the Impact of Missed Doses of Venous Thromboembolism Prophylaxis'; receives research grant support from the DOD/Army Medical Research Acquisition Activity and has received grant support from the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); receives book royalties from Lippincott, Williams, Wilkins; and is a paid consultant to Vizient for their HIIN Venous Thromboembolism (VTE) Prevention Action Network.
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