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 "ELAN"

Recruiting

Phase N/A Results N/A

Trial Description

When to start anticoagulation in patients with an acute ischaemic stroke and atrial fibrillation (AF) is a relevant unanswered question in clinical practice. Direct oral anticoagulants (DOACs) are highly effective for secondary stroke prevention in these patients, but DOACs were never initiated <7 days after stroke onset in recent trials. The ELAN trial will determine the net benefit of early versus late initiation of DOACs in patients with acute ischaemic stroke related to AF.
The main objective is to estimate the net benefit of early versus late initiation of DOACs in patients with acute ischaemic stroke related to AF.
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.

Detailed Description

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia increasing the risk of stroke and systemic thromboembolism and thus mortality and morbidity. Anticoagulation therapy, such as with vitamin K antagonists effectively prevents strokes in patients with AF, however, increases bleeding complications leading to symptomatic intracerebral haemorrhage. Direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists in preventing recurrent strokes, but with lower rates of symptomatic intracerebral haemorrhage. Therefore, these new agents are potentially ideal drugs to treat patients with ischaemic stroke related to AF. However, in previous trials comparing DOACs with vitamin K antagonists, therapy was initiated later than 7-14 days after onset of ischaemic stroke. Whether, earlier initiation of DOACs may prevent recurrent stroke without increasing the risk of symptomatic intracerebral haemorrhage remains to be determined.
Objectives The main objective is to estimate the net benefit of early versus late initiation of DOACs in patients with acute ischaemic stroke related to AF.
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.
Methods All patients of 18 years or older with an acute ischaemic stroke related to AF should be screened for this trial.
Patients in the experimental arm (early treatment) and the control arm (late treatment) will receive direct oral anticoagulants for prevention of stroke and systemic embolism in patients with AF. Depending on the size of the infarction, early treatment will be started within 48 hours after symptom onset (minor and moderate ischaemic stroke) or at day 6 + 1 day after symptom onset (major ischaemic stroke). Patients in the control arm will receive late treatment as per current recommendations (i.e. minor ischaemic stroke after day 3 + 1 day, moderate ischaemic stroke after day 6 + 1 day and major ischaemic stroke after day 12 + 2 day).
The primary outcome is a composite of major bleeding, recurrent ischaemic stroke, systemic embolism and/or vascular death at 30 ± 3 days after randomisation.

Conditions

Interventions

Outcomes

Type Measure Time Frame Safety Issue
Primary Composite of major bleeding, recurrent ischaemic stroke, systemic embolism and/or vascular death 30 ± 3 days after randomisation
Secondary Modified Rankin Scale (mRS) 30 days, 90 days after randomisation
Secondary Major bleeding 90 days after randomisation
Secondary Recurrence of stroke 90 days after randomisation
Secondary Systemic embolism 90 days after randomisation
Secondary Vascular death 90 days after randomisation
Secondary All-cause mortality 90 days after randomisation
Secondary Myocardial infarction 90 days after randomisation
Secondary Major cardiovascular events defined as composite of stroke, myocardial infarct, heart failure or cardiovascular death 90 days after randomisation
Secondary Silent brain lesions defined as ischemic lesions of the brain parenchyma detected on brain MRI 90 days after randomisation
Secondary mRS score of 0-2 versus 3-6 90 days after randomisation
Secondary NIHSS 90 days after randomisation
Secondary Compliance monitored with a patient diary documenting daily intake of direct oral anticoagulants 90 days after randomisation
Secondary Non-major bleeding 30 days, 90 days after randomisation
Secondary Silent brain lesions 90 days after randomisation
Secondary Favourable outcome defined as mRS ≤ 2 and shift analysis adjusted to premorbid mRS 90 days after randomisation
Secondary Transient ischemic attack 30 days, 90 days after randomisation
Secondary Undetermined stroke 30 days, 90 days after randomisation
Secondary Compliance 30 days after randomisation

Sponsors