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 Kelly, Robin Lemmens, Masatoshi Koga, Padmavathy N. SylajaDiana Aguiar de Sousa, Natan M. Bornstein, Zuzana Gdovinova, David J. Seiffge, Jan Gralla, Thomas Horvath, Jesse Dawson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)487-495
Number of pages9
JournalEuropean Stroke Journal
Volume7
Issue number4
DOIs
StatePublished - Dec 2022
Externally publishedYes

Funding

FundersFunder number
Neuro Clinical Trial Unit
Abbott Laboratories
Medtronic
České Vysoké Učení Technické v Praze
CSL Behring
Schweizerischen Neurologischen Gesellschaft
National Cerebral and Cardiovascular Center
Stroke Association2017/02, 20-4-5
Indian Council of Medical Research
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung32003B_169975, 32003B_197009
Schweizerische Herzstiftung

    Keywords

    • Atrial fibrillation
    • DOAC
    • acute ischaemic stroke
    • anticoagulation
    • timing

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