HIP Fracture Oral thromboPROphylaxis (Hip PRO Pilot)

1. Background: With over 30,000 hip fractures in Canada annually, these injuries are an epidemic. Venous thromboembolism (VTE) events are common following hip fracture surgery (HFS) and include life-threatening pulmonary embolism (PE; a leading cause of preventable mortality) and debilitating deep vein thromboses (DVTs; second most common complication). Thromboprophylaxis reduces VTE, but the optimal medication remains unknown. Low molecular weight heparin (LMWH) has been the mainstay, but adherence is poor: only 1 in 5 patients adhere after HFS, limiting its effectiveness. Meta-analyses support that direct oral anticoagulants (DOACs) are as effective as LMWH in prevention of VTE, but the data are limited by borderline effect sizes, small sample sizes, and inconsistent outcomes. Our survey found that surgeons report safety concerns and are reluctant to use DOACs due to post-operative bleeding risk. Our research demonstrates platelet-dominant hypercoagulability using serial thrombelastography (TEG), reduced platelet activity with aspirin (ASA) use, and maybe increasing comfort with prescribing ASA post-HFS. Randomized controlled trials (RCTs) comparing LMWH and ASA post-injury are limited by non-standardized therapy duration, asymptomatic DVT inclusion, and patient heterogeneity. ASA has been favourably compared to DOACs and LMWH in arthroplasty RCTs examining oral thromboprophylaxis following total hip and total knee arthroplasty. Continued morbidity and mortality, patient and surgeon preference, and our network meta-analysis support the need for comparison between DOAC and ASA for VTE prevention after HFS. Based on our research, our resent network meta-analysis supporting oral thromboprophylaxis, along with patient preference for oral medications, there is a need for comparison between DOAC and ASA for prevention of VTE to reduce the continued morbidity and mortality that ensues following HFS.
2. Objectives:

Specific Aims:

1. Feasibility: This pilot trial will evaluate the feasibility of a full-scale RCT comparing the safety and efficacy of rivaroxaban versus ASA for thromboprophylaxis after HFS, based on achieving recruitment targets, study drug adherence, and participant retention.
2. Safety and Efficacy: Key clinical data will be collected to estimate VTE and bleeding complications to inform the full-scale RCT. (3) Methods:

This is a multi-centre double-blind pilot trial consisting of consecutive eligible patients 50 years or older requiring HFS who will be randomized (1:1) via web-based randomization to rivaroxaban 10 mg daily for 35 days or ASA 81 mg daily for 35 days, with 90-day follow-up. The primary feasibility outcome measure is an estimate of the mean monthly recruitment rate over 12 months across participating sites, including 95% confidence intervals, with a priori feasibility criteria determining progression to the full trial. Secondary feasibility outcomes are consent and retention rates, and drug adherence.

Secondary clinical outcomes will include symptomatic VTE, major bleeding, clinically relevant non-major bleeding, and 90-day mortality (independently and blindly adjudicated). Intention-to-treat analysis will be used, and subgroup analysis will compare age, sex, gender, and surgical type. Additional patient-reported (the Cumulated Ambulation Score and Clinical Frailty Scale), value-based (direct and indirect costs) and translational (coagulation) outcomes will be included.