ENhanced Recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty

An increasing proportion of the ageing population in Europe and other parts of the world suffers from hip osteoarthritis and will need surgical joint arthroplasty at some time in their lives. Surgical total hip arthroplasty (THA) is associated with a high risk of venous thromboembolism (VTE), but the appropriate duration of postoperative anticoagulation remains highly controversial. Although current German guidelines continue to advocate anticoagulation for 28-35 days after THA, clinical practice recommendations in other countries are shifting towards much earlier discontinuation of anticoagulants - despite the absence of solid evidence backed by controlled data. The "Enhanced recovery and Abbreviated duration of Anticoagulation for thromboprophylaxis after primary hip Arthroplasty" (ENABLE-Hip) study is a multicentre investigator-initiated and academically sponsored prospective randomised active-control non-inferiority trial. A regimen of short-duration (10-day) prophylactic anticoagulation (experimental arm) will be compared to standard-duration (35-day) anticoagulation as per current guidelines (control arm). Patients will be mobilised early after surgery, following a standardised enhanced recovery protocol. Following randomisation and an initial two-day open-label period of prophylactic anticoagulation as per local protocol, treatment with the study drug (rivaroxaban at the standard, approved prophylactic dose of 10 mg daily) will be started and continued until 10 days after surgery. After this time, patients will be switched (in a double-blinded manner) to placebo in the experimental arm, or continue on active drug in the control arm, until a total of 35 days have elapsed since surgery. The primary outcome is acute symptomatic proximal deep vein thrombosis (DVT), or symptomatic or fatal pulmonary embolism (PE), within the first 3 months after surgery. Participating investigators will be advised to adhere to guideline recommendations regarding clinical suspicion of and diagnostic work-up for VTE. The planned study population of 2,932 patients will provide ≥ 80% power to reject the null hypothesis that δ ≥ 0.01 (where δ = difference between the two arms in symptomatic VTE probability within 3 months) and accept the alternative hypothesis that δ < 0.01, at an overall significance level α = 0.05. A formal interim analysis will be performed after 3-month follow-up of the first 1,760 randomised patients at a significance level α = 0.50, leading to stopping for futility if significance is not obtained, or if recalculation yields an overall sample size of > 3,200 patients. The trial has the potential to inform future national and European guidelines for this large and continuously growing patient population.