Reperfusion thrombolytic therapy for ischemic stroke in patients on non-vitamin K antagonist oral anticoagulants: study protocol of a phase II randomized clinical trial

Background Cardioembolic stroke accounts for more than 20% of all acute ischemic strokes (AIS) and is mainly caused by cardiac arrhythmias, particularly atrial fibrillation (AF). The presence of specific or multiple additional vascular risk factors indicates the need for oral anticoagulant (OAC) therapy in AF patients (according to the CHA2DS2-VASc classification). While OAC treatment significantly reduces the risk of AIS by over 80% in this population, the risk remains higher compared to the general population. Approximately half of AF patients on OAC therapy who experience AIS do not meet the criteria for thrombolytic (high blood activity of OAC) or mechanical thrombectomy (non-large vessel occlusion stroke) treatment. Aim This study aims to assess the efficacy and safety of recombinant tissue plasminogen activator (rtPA) in AIS patients who have been on chronic non-vitamin K antagonist oral anticoagulant (DOAC) therapy after receiving a specific reversal agent. Methods and design Patients with acute ischemic stroke (AIS) who are treated with specific oral anticoagulants (OACs) with anti-Xa activity ≥50 ng/ml and are not eligible for mechanical thrombectomy will be included in the study. The protocol involves administering a fast-acting antidote (andexanet alfa for rivaroxaban or apixaban) or a placebo, followed by intravenous thrombolytic therapy with rtPA or a placebo. The study arms for rivaroxaban and apixaban are designed as prospective, randomized, placebo-controlled interventional trials that meet phase II trial criteria. Discussion The STRoke on Oral AntiCoagulants for Thrombolysis (STROACT) trial is the first randomized clinical trial investigating the impact of intravenous thrombolysis with rtPA in AIS patients on chronic DOAC therapy. Trial registration www.clinicaltrialsregister.eu; EudraCT Nr: 2020-004898-41; March 31, 2021.