Restarting anticoagulation early versus late in patients with chronic subdural hematoma and atrial fibrillation (RELACS): a phase III international multicenter, randomized controlled, two-arm, assessor-blinded trial

Abstract

<h3>Background</h3><p>Chronic subdural hematoma (CSDH) is a rapidly growing neurosurgical condition, driven primarily by an aging population and the increasing use of antithrombotic medications. Approximately 25% of CSDH patients are on anticoagulants due to atrial fibrillation (AF). The postoperative management of these patients presents a significant clinical challenge, as clinicians must balance the risks of thromboembolic and hemorrhagic complications. Currently, no evidence-based guidelines exist regarding the optimal timing for resuming anticoagulation therapy after surgery. This study aims to evaluate the net effect of early versus late postoperative resumption of oral anticoagulation in CSDH patients with AF. We hypothesize that early resumption will result in fewer thromboembolic complications and vascular deaths, without increasing the risk of hemorrhagic complications.</p><h3>Methods</h3><p>This is an investigator-initiated, international, multicenter, superiority, two-arm, assessor-blinded, phase 3 trial with 1:1 randomization, comparing early resumption (defined as 5 days) and late resumption (defined as 30 days) of oral anticoagulation medication after CSDH surgery in patients with AF. The primary outcome is a composite outcome that combines thromboembolic events, hemorrhagic events, and vascular death within 90 days of the surgery. Secondary outcomes include reoperations, functional outcome, and adverse events. The estimated sample size is 332 patients to achieve an 80% power and a two-sided alpha of 0.05 for the primary outcome, including potential dropouts.</p><h3>Discussion</h3><p>This is the first large-scale RCT addressing the critical evidence gap in anticoagulation timing after CSDH surgery. If early resumption proves superior, it could transform clinical practice by reducing thromboembolic complications without increasing hemorrhagic risk, potentially improving outcomes for the growing population of CSDH patients with AF worldwide.</p><h3>Trial registration</h3><p>The study is registered on June 4, 2025. The EU Clinical Trials Register (EUCTR) under identifier EUCT 2025-521179-29-00 (<a href="https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-521179-29-00">https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-521179-29-00</a>).</p>