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
NCT ID: NCT03148457
Last Updated: 2023-07-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
2013 participants
INTERVENTIONAL
2017-11-06
2023-05-24
Brief Summary
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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.
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Early treatment
Early treatment of patients with ischaemic stroke related to atrial fibrillation (AF) with direct oral anticoagulations (DOACs).
Early treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)
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)
Late treatment
Treatment with direct oral anticoagulations (DOACs) according the current standard practice in patients with acute ischemic stroke related to atrial fibrillation (AF).
Late treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)
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).
Interventions
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Early treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)
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)
Late treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)
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).
Eligibility Criteria
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Inclusion Criteria
* 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
* Valvular disease requiring surgery
* Mechanical heart valve(s)
* Moderate or severe mitral stenosis. Please note that other valvular diseases and biological valves are eligible
* 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
18 Years
ALL
No
Sponsors
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Insel Gruppe AG, University Hospital Bern
OTHER
Responsible Party
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Principal Investigators
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Urs Fischer, Prof. MD
Role: PRINCIPAL_INVESTIGATOR
Dept. of Neurology, Inselspital Bern
Locations
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Krankenhaus der Barmherzigen Brüder Eisenstadt
Eisenstadt, , Austria
Medizinische Universität Graz
Graz, , Austria
Kepler Universitätsklinikum, Klinik für Neurologie 1
Linz, , Austria
Kepler Universitätsklinikum, Klinik für Neurologie 2
Linz, , Austria
Universitätsklinikum St. Pölten
Sankt Pölten, , Austria
Universitätsklinikum Tulln
Tulln, , Austria
Medizinische Universität Wien
Vienna, , Austria
Onze-Lieve-Vrouw Ziekenhuis VZW
Aalst, , Belgium
Cliniques Universitaires Saint-Luc
Brussels, , Belgium
Antwerp University Hospital
Edegem, , Belgium
University Hospital Gent
Ghent, , Belgium
AZ Groeninge
Kortrijk, , Belgium
UZ Leuven
Leuven, , Belgium
CHC - Saint Joseph
Liège, , Belgium
Cliniques de l'Europe - Site Ste-Elisabeth
Uccle, , Belgium
Helsinki University Hospital
Helsinki, , Finland
Siun sote - North Karelia social and health services
Joensuu, , Finland
Universitätsklinikum Leipzig
Leipzig, Saxony, Germany
Vivantes Klinikum Neukölln
Berlin, , Germany
St. Josef-Hospital Bochum
Bochum, , Germany
Klinik und Poliklinik für Neurologie Köln
Cologne, , Germany
Universitätsklinikum Erlangen
Erlangen, , Germany
Universitätsklinikum Frankfurt
Frankfurt, , Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, , Germany
Neurologische Universitätsklinik Heidelberg
Heidelberg, , Germany
Universitätsklinikum Schleswig-Holstein
Lübeck, , Germany
Mannheim University Hospital
Mannheim, , Germany
Klinikum der Universität München
München, , Germany
Universitäsklinikum Tübingen
Tübingen, , Germany
Dept. of Medicine, University of Thessaly
Larissa, Thessaly, Greece
Lalitha Super Speciality Hospitals
Kothapeta, Guntur, India
Narayana Hrudayalaya Bangalore
Bengaluru, Karnataka, India
Amrita Institute of Medical Sciences
Kochi, Kerala, India
Government Medical College Thiruvananthapuram
Thiruvananthapuram, Kerala, India
Sree Chitra Tirunal Institute for Medical Sciences and Technology
Trivandrum, Kerala, India
All India Institute Of Medical Sciences
New Delhi, National Capital Territory of Delhi, India
Christian Medical College & Hospital
Ludhiana, Punjab, India
Cork University Hospital
Cork, , Ireland
Mater Misericordiae University Hospital
Dublin, , Ireland
St. James's Hospital
Dublin, , Ireland
St. Vincent's University Hospital
Dublin, , Ireland
Tallaght University Hospital
Dublin, , Ireland
University Hospital Waterford
Waterford, , Ireland
Hadassah Medical Center
Jerusalem, , Israel
Shaare Zedek Medical Center
Jerusalem, , Israel
Sheba Medical Centre
Ramat Gan, , Israel
Ospedale Santa Maria della Misericordia
Perugia, , Italy
Umberto Policlinico di Roma
Rome, , Italy
Kansai Medical University
Hirakata, , Japan
St. Marianna Medical University Hospital
Kawasaki, , Japan
Kumamoto University
Kumamoto, , Japan
National Cerebral and Cardiovascular Center
Osaka, , Japan
Jichi Medical University
Tochigi, , Japan
The Jikei University Hospital
Tokyo, , Japan
Ålesund sjukehus
Ålesund, , Norway
Vestre Viken Health Trust - Drammen Hospital
Drammen, , Norway
Akershus University Hospital
Lørenskog, , Norway
Oslo University Hospital, Ullevål
Oslo, , Norway
Coimbra University Hospital
Coimbra, , Portugal
Hospital de Santa Maria
Lisbon, , Portugal
Hospital de Egas Moniz
Lisbon, , Portugal
Košice Medical University
Košice, , Slovakia
Fakultná Nemocnica Trnava
Trnava, , Slovakia
Dept. of Neurology, Kantonsspital Aarau
Aarau, Canton of Aargau, Switzerland
Dept. of Neurology, Universitätsspital Basel
Basel, Canton of Basel-City, Switzerland
Dept. of Neurology, Universitätsspital Lausanne
Lausanne, Canton of Vaud, Switzerland
Dept. of Neurology, Hôpital de Zone de Nyon
Nyon, Canton of Vaud, Switzerland
Dept. of Neurology, Kantonsspital Chur
Chur, Kanton Graubünden, Switzerland
Dept. of Neurology, Kantonsspital Sion
Sion, Valais, Switzerland
Kantonsspital Baden
Baden, , Switzerland
Dept. of Neurology, Bern University Hospital
Bern, , Switzerland
Dept. of Neurology, Kantonsspital Fribourg
Fribourg, , Switzerland
Dept. of Neurology, Universitätsspital Genf
Geneva, , Switzerland
Dept. of Neurology, Kantonsspital Luzern
Lucerne, , Switzerland
Ospedale Regionale di Lugano (EOC)
Lugano, , Switzerland
Kantonsspital Münsterlingen
Münsterlingen, , Switzerland
Hôpital neuchâtelois
Neuchâtel, , Switzerland
Dept. of Neurology, Kantonsspital St.Gallen
Sankt Gallen, , Switzerland
Kantonsspital Winterthur
Winterthur, , Switzerland
Klinik Hirslanden Zürich
Zurich, , Switzerland
Dept. of Neurology, Universitätsspital Zürich
Zurich, , Switzerland
St George's University Hospitals NHS Foundation Trust
Tooting, London, United Kingdom
University Hospital Monklands
Airdrie, , United Kingdom
Royal United Hospitals Bath
Bath, , United Kingdom
Southmead Hospital Bristol
Bristol, , United Kingdom
Countess of Chester Hospital
Chester, , United Kingdom
Ninewells Hospital
Dundee, , United Kingdom
University Hospital of North Durham
Durham, , United Kingdom
Glasgow Royal Infirmary
Glasgow, , United Kingdom
Queen Elizabeth University Hospital
Glasgow, , United Kingdom
Wirral University Teaching Hospital
Metropolitan Borough of Wirral, , United Kingdom
The James Cook University Hospital
Middlesbrough, , United Kingdom
Morriston Hospital
Morriston, , United Kingdom
Perth Royal Infirmary
Perth, , United Kingdom
Glan Clwyd Hospital
Rhyl, , United Kingdom
University Hospital of North Tees
Stockton-on-Tees, , United Kingdom
Royal Stoke University Hospital
Stoke-on-Trent, , United Kingdom
Weston General Hospital
Weston-super-Mare, , United Kingdom
Countries
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References
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Polymeris AA, Rossel JB, Koga M, Strbian D, Vedamurthy A, Krishnan M, Branca M, Meinel T, Kristoffersen ES, Yoshimoto T, Tanaka K, Kunieda T, Yakushiji Y, Vehoff J, Matsuzono K, Slade P, Demeestere J, Salerno A, Caracciolo NG, Hemelsoet D, Engelter ST, Auer E, Horvath T, Seiffge DJ, Goeldlin M, Dawson J, Fischer U; ELAN Investigators. Once- versus twice-daily direct oral anticoagulants after ischemic stroke in atrial fibrillation - A post-hoc analysis of the ELAN trial. Eur Stroke J. 2025 Aug 11:23969873251360974. doi: 10.1177/23969873251360974. Online ahead of print.
Wouters A, Demeestere J, Rossel JB, Devroye A, Desfontaines P, Vanacker P, Hemelsoet D, Yperzeele L, Rutgers MP, Peeters A, Vynckier J, Yoshimoto T, Tanaka K, Vehoff J, Matsuzono K, Kulyk C, Sibolt G, Slade P, Salerno A, Kunieda T, Hakim A, Rohner R, Abend S, Goeldlin M, Dawson J, Fischer U, Lemmens R; ELAN Investigators. Prior Reperfusion Strategy Does Not Modify Outcome in Early Versus Late Start of Anticoagulants in Patients With Ischemic Stroke: Prespecified Subanalysis of the Randomized Controlled ELAN Trial. Stroke. 2025 Aug;56(8):2000-2008. doi: 10.1161/STROKEAHA.125.050646. Epub 2025 May 22.
Kneihsl M, Hakim A, Goeldlin MB, Branca M, Fenzl S, Abend S, Gattringer T, Enzinger C, Dawson J, Gesierich B, Kopczak A, Hack RJ, Cerfontaine MN, Rutten JW, Lesnik Oberstein SAJ, Pasi M, Fischer U, Duering M, Meinel TR. Topographic Localization of Chronic Cerebellar Ischemic Lesions: Implications for Underlying Cause. Stroke. 2025 Jul;56(7):1823-1831. doi: 10.1161/STROKEAHA.124.049337. Epub 2025 Apr 3.
Polymeris AA, Branca M, Sylaja PN, Sandset EC, de Sousa DA, Thomalla G, Paciaroni M, Gattringer T, Strbian D, Trelle S, Michel P, Nedeltchev K, Bonati LH, Ntaios G, Koga M, Gdovinova Z, Lemmens R, Bornstein NM, Kelly P, Goeldlin MB, Abend S, Selim M, Katan M, Horvath T, Dawson J, Fischer U; ELAN Investigators. Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial. JAMA Netw Open. 2025 Jan 2;8(1):e2456307. doi: 10.1001/jamanetworkopen.2024.56307.
Kneihsl M, Hakim A, Goeldlin MB, Meinel TR, Branca M, Rohner R, Fenzl S, Abend S, Shim GC, Gumbinger C, Zhang L, Kristoffersen ES, Desfontaines P, Vanacker P, Alonso A, Poli S, Nunes AP, Caracciolo NG, Gattringer T, Kahles T, Giudici D, Demeestere J, Dawson J, Fischer U; ELAN investigators. Early vs Late Anticoagulation After Ischemic Stroke in Patients With Atrial Fibrillation and Covert Brain Infarcts. Neurology. 2025 Jan 14;104(1):e210157. doi: 10.1212/WNL.0000000000210157. Epub 2024 Dec 19.
Goeldlin MB, Hakim A, Branca M, Abend S, Kneihsl M, Valenzuela Pinilla W, Fenzl S, Rezny-Kasprzak B, Rohner R, Strbian D, Paciaroni M, Thomalla G, Michel P, Nedeltchev K, Gattringer T, Sandset EC, Bonati L, Aguiar de Sousa D, Sylaja PN, Ntaios G, Koga M, Gdovinova Z, Lemmens R, Bornstein NM, Kelly P, Katan M, Horvath T, Dawson J, Fischer U; ELAN Investigators. Early vs Late Anticoagulation in Minor, Moderate, and Major Ischemic Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial. JAMA Neurol. 2024 Jul 1;81(7):693-702. doi: 10.1001/jamaneurol.2024.1450.
Rohner R, Kneihsl M, Goeldlin MB, Hakim A, Branca M, Abend S, Valenzuela Pinilla W, Fenzl S, Rezny-Kasprzak B, Strbian D, Trelle S, Paciaroni M, Thomalla G, Michel P, Nedeltchev K, Gattringer T, Sandset EC, Bonati L, Aguiar de Sousa D, Sylaja PN, Ntaios G, Koga M, Gdovinova Z, Lemmens R, Bornstein NM, Kelly P, Katan M, Horvath T, Dawson J, Fischer U; ELAN Investigators. Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial. Circulation. 2024 Jul 2;150(1):19-29. doi: 10.1161/CIRCULATIONAHA.124.069324. Epub 2024 May 16.
Fischer U, Koga M, Strbian D, Branca M, Abend S, Trelle S, Paciaroni M, Thomalla G, Michel P, Nedeltchev K, Bonati LH, Ntaios G, Gattringer T, Sandset EC, Kelly P, Lemmens R, Sylaja PN, Aguiar de Sousa D, Bornstein NM, Gdovinova Z, Yoshimoto T, Tiainen M, Thomas H, Krishnan M, Shim GC, Gumbinger C, Vehoff J, Zhang L, Matsuzono K, Kristoffersen E, Desfontaines P, Vanacker P, Alonso A, Yakushiji Y, Kulyk C, Hemelsoet D, Poli S, Paiva Nunes A, Caracciolo N, Slade P, Demeestere J, Salerno A, Kneihsl M, Kahles T, Giudici D, Tanaka K, Raty S, Hidalgo R, Werring DJ, Goldlin M, Arnold M, Ferrari C, Beyeler S, Fung C, Weder BJ, Tatlisumak T, Fenzl S, Rezny-Kasprzak B, Hakim A, Salanti G, Bassetti C, Gralla J, Seiffge DJ, Horvath T, Dawson J; ELAN Investigators. Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. N Engl J Med. 2023 Jun 29;388(26):2411-2421. doi: 10.1056/NEJMoa2303048. Epub 2023 May 24.
Other Identifiers
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2017-00588
Identifier Type: -
Identifier Source: org_study_id
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