Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): Protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial
Urs Fischer, Sven Trelle, Mattia Branca, Georgia Salanti, Maurizio Paciaroni, Cecilia Ferrari, Stefanie Abend, Seraina Beyeler, Daniel Strbian, Götz Thomalla, George Ntaios, Leo H. Bonati, Patrik Michel, Krassen Nedeltchev, Thomas Gattringer, Else Charlotte Sandset, Peter J. Kelly, Robin Lemmens, Masatoshi Koga, Padmavathy N. Sylaja, Diana Aguiar de Sousa, Natan M. Bornstein, Zuzana Gdovinová, David Seiffge, Jan Gralla, Thomas Horvath, Jesse Dawson, on behalf of the ELAN Investigators
Abstract
Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6-7 following major stroke. Late treatment is defined as DOAC initiation after day 3-4 following minor stroke, after day 6-7 following moderate stroke and after day 12-14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.