Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): an international, multicentre, randomised-controlled, two-arm, assessor-blinded trial

Phase 1

• Conditions: Recurrent strokes in patients with atrial fibrillation who suffered an ischaemic stroke; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-000236-34-FI
• Lead Sponsor: Inselspital (University Hospital) Bern

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-12-21
• Last Update Posted: 2 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Participants fulfilling all of the following inclusion criteria are eligible for the trial:
• Written informed consent according to country specific details (see table 1 and 2 of section 2.7)
• Age: =18 years
• Acute ischaemic stroke, either confirmed by MRI or CT scan (tissue based definition) or by sudden focal neurological deficit of presumed ischaemic origin that persisted beyond 24 hours and otherwise normal non-contrast CT scan. Please note: prior intravenous or endovascular treatment is allowed.
• Permanent, persistent, or paroxysmal spontaneous AF previously known or diagnosed during the index hospitalization
• Agreement of treating physician to prescribe DOACs
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1500

Exclusion Criteria

The presence of any one of the following exclusion criteria will lead to exclusion of the participant:
• Atrial fibrillation due to reversible causes (e.g. thyrotoxicosis, pericarditis, recent surgery, myocardial infarct)
• Valvular disease requiring surgery
• Mechanical heart valve(s)
• Moderate or severe rheumatic mitral stenosis. Please note that other valvular diseases and biological valves are eligible
• Conditions other than AF that require anticoagulation, including therapeutical dose of low-molecular-weight heparin or heparin
• Anticoagulation above the relevant thresholds at ischaemic stroke onset or at hospital admission as follows:
o Vitamine K antagonist: International Normalized Ratio (INR) = 1.7, or
o Anti-IIa: thrombin time = 80 seconds and/or anti-IIa = 100 ng/ml and/or aPTT value > 1.5x normal, or
o Anti-Xa: anti-Xa = 100 ng/ml or = 0.7 U/ml
• Subject who is contraindicated to DOACs
• Female with a positive pregnancy test at time of randomization, with a suspicion of pregnancy, or lactating
• Patients with serious bleeding in the last 6 months or at high risk of bleeding (e.g. active peptic ulcer disease, platelet count < 100’000/mm3 or haemoglobin < 10 g/dl or INR = 1.7, documented haemorrhagic tendencies or blood dyscrasias)
• Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
• Severe comorbid condition with life expectancy < 6 months
• Severe renal impairment as described in the summary of medicinal product characteristics for the chosen DOAC (e.g. Rivaroxaban, Apixaban and Edoxaban creatinine clearance <15 ml/min, Dabigatran creatinine clearance <30 ml/min)
• Subject who requires haemodialysis or peritoneal dialysis
• Subject with aortic dissection
• Current participation in another investigational trial
• Dual antiplatelet therapy (DAPT) at baseline or strong likelihood to be treated with dual antiplatelet therapy during the course of the trial, Please note: transient DAPT is not an exclusion criterion if DAPT is stopped prior to randomisation
• CT or MRI evidence of haemorrhage classified as PH1 (defined as parenchymal haemorrhage = blood clots in < 30% of the infarcted area without or with slight space-occupying effect) and PH2 (defined as blood clots in > 30% of the infarcted area with a substantial space-occupying effect) independently of clinical deterioration. Please note that HI1 (defined as haemorrhagic infarct = small petechiae along the margins of the infarct) and HI2 (defined as confluent petechiae within the infarcted area but no space occupying effect) are acceptable if not associated with clinical deterioration and if the treating physician feels comfortable to treat patients with DOACs.
• CT or MRI evidence of mass effect or intra-cranial tumour (except small meningioma)
• CT or MRI evidence of cerebral vasculitis
• Endocarditis
• Evidence of severe cerebral amyloid angiopathy if MRI scan performed

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective is to determine the net benefit of early versus late initiation of DOACs in patients with acute ischaemic stroke related to AF. Net benefit is estimated by a composite outcome that combines the outcomes of interest (recurrent ischaemic stroke and systemic embolism) to estimate efficacy and the bleeding outcomes of interest (symptomatic intracranial haemorrhaege and major extracranial bleeding) as well as vascular death to estimate safety.;Secondary Objective: The secondary objectives are to assess all vascular events and all-cause mortality after early initiation of DOACs in patients with acute ischaemic stroke related to AF compared to late initiation.;Primary end point(s): The primary outcome is the composite of major extracranial bleeding, symptomatic intracranial haemorrhage, recurrent ischaemic stroke, systemic embolism, and/or vascular death at 30 ± 3 days after randomisation.;Timepoint(s) of evaluation of this end point: 30 ± 3 days after randomisation.