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

• Register: ClinicalTrials.gov
• Last refreshed on: 2 August 2023
• Main ID: NCT03148457
• Date of registration: 07/04/2017
• Prospective Registration: Yes
• Primary sponsor: Insel Gruppe AG, University Hospital Bern
• Public title: 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
• Scientific title: 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
• Date of first enrolment: November 6, 2017
• Target sample size: 2013
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03148457
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: N/A

Countries of recruitment

Austria, Belgium, Finland, Germany, Greece, India, Ireland, Israel, Italy, Japan, Norway, Portugal, Slovakia, Switzerland, United Kingdom

Contacts

• Name: Urs Fischer, Prof. MD
• Affiliation: Dept. of Neurology, Inselspital Bern

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written informed consent according to country specific details

- Age: =18 years

- Acute ischemic 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

Exclusion Criteria:

- 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 mitral stenosis. Please note that other valvular diseases and
biological valves are eligible

- AF and conditions other than AF that require anticoagulation, including therapeutical
dose of low-molecular-weight heparin or heparin. Please note: infratherapeutic
anticoagulation at ischaemic stroke onset defined as follows is not an exclusion
criteria:

- Vitamine K antagonist: International Normalized Ratio (INR) <1.7

- Anti-IIa: thrombin time <80 seconds and/or anti-IIa <50 ng/ml

- Anti-Xa: anti-Xa <50 ng/ml

- Subject who is contraindicated to DOACs

- Female who is pregnant or lactating or has a positive pregnancy test at time of
admission

- Patients with serious bleeding in the last 6 months or is 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
(defined as regular or daily consumption of more than four alcoholic drinks per day)

- Severe comorbid condition with life expectancy < 6 months

- Severe or moderate renal insufficiency as defined by creatinine clearance < 50 ml/min

- Subject who requires haemodialysis or peritoneal dialysis

- Subject with aortic dissection

- Current participation in another investigational trial

- Dual antiplatelet therapy at baseline or strong likelihood to be treated with dual
antiplatelet therapy during the course of the trial

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Ischaemic Stroke

Intervention(s)

Drug: Early treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)

Drug: Late treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)

Primary Outcome(s)

Composite of major bleeding, recurrent ischaemic stroke, systemic embolism and/or vascular death [Time Frame: 30 ± 3 days after randomisation]

Secondary Outcome(s)

Recurrence of stroke [Time Frame: 30 days, 90 days after randomisation]

Major cardiovascular events defined as composite of stroke, myocardial infarct, heart failure or cardiovascular death [Time Frame: 90 days after randomisation]

Major bleeding [Time Frame: 30 days, 90 days after randomisation]

NIHSS [Time Frame: 90 days after randomisation]

Myocardial infarction [Time Frame: 90 days after randomisation]

Silent brain lesions [Time Frame: 90 days after randomisation]

Compliance [Time Frame: 30 days after randomisation]

Modified Rankin Scale (mRS) [Time Frame: 30 days, 90 days after randomisation]

Non-major bleeding [Time Frame: 30 days, 90 days after randomisation]

Systemic embolism [Time Frame: 30 days, 90 days after randomisation]

All-cause mortality [Time Frame: 90 days after randomisation]

Favourable outcome defined as mRS = 2 and shift analysis adjusted to premorbid mRS [Time Frame: 90 days after randomisation]

Undetermined stroke [Time Frame: 30 days, 90 days after randomisation]

Vascular death [Time Frame: 30 days, 90 days after randomisation]

Transient ischemic attack [Time Frame: 30 days, 90 days after randomisation]

Secondary ID(s)

2017-00588

Source(s) of Monetary Support

Please refer to primary and secondary sponsors