Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    ELAN stroke
Previous Study | Return to List | Next Study

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03148457
Recruitment Status : Recruiting
First Posted : May 11, 2017
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Tracking Information
First Submitted Date  ICMJE April 7, 2017
First Posted Date  ICMJE May 11, 2017
Last Update Posted Date September 16, 2019
Actual Study Start Date  ICMJE November 6, 2017
Estimated Primary Completion Date August 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2017)
Composite of major bleeding, recurrent ischaemic stroke, systemic embolism and/or vascular death [ Time Frame: 30 ± 3 days after randomisation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03148457 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
  • Modified Rankin Scale (mRS) [ Time Frame: 30 days, 90 days after randomisation ]
  • Major bleeding [ Time Frame: 30 days, 90 days after randomisation ]
  • Non-major bleeding [ Time Frame: 30 days, 90 days after randomisation ]
  • Recurrence of stroke [ Time Frame: 30 days, 90 days after randomisation ]
  • Systemic embolism [ Time Frame: 30 days, 90 days after randomisation ]
  • Vascular death [ Time Frame: 30 days, 90 days after randomisation ]
  • All-cause mortality [ Time Frame: 90 days after randomisation ]
  • Myocardial infarction [ Time Frame: 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 ]
  • Silent brain lesions [ Time Frame: 90 days after randomisation ]
    If CT/MRI is performed in clinical routine
  • Favourable outcome defined as mRS ≤ 2 and shift analysis adjusted to premorbid mRS [ Time Frame: 90 days after randomisation ]
  • NIHSS [ Time Frame: 90 days after randomisation ]
  • Transient ischemic attack [ Time Frame: 30 days, 90 days after randomisation ]
  • Undetermined stroke [ Time Frame: 30 days, 90 days after randomisation ]
  • Compliance [ Time Frame: 30 days after randomisation ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2017)
  • Modified Rankin Scale (mRS) [ Time Frame: 30 days, 90 days after randomisation ]
  • Major bleeding [ Time Frame: 90 days after randomisation ]
  • Recurrence of stroke [ Time Frame: 90 days after randomisation ]
  • Systemic embolism [ Time Frame: 90 days after randomisation ]
  • Vascular death [ Time Frame: 90 days after randomisation ]
  • All-cause mortality [ Time Frame: 90 days after randomisation ]
  • Myocardial infarction [ Time Frame: 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 ]
  • Silent brain lesions defined as ischemic lesions of the brain parenchyma detected on brain MRI [ Time Frame: 90 days after randomisation ]
    If MRI is performed in clinical routine
  • mRS score of 0-2 versus 3-6 [ Time Frame: 90 days after randomisation ]
  • NIHSS [ Time Frame: 90 days after randomisation ]
  • Compliance monitored with a patient diary documenting daily intake of direct oral anticoagulants [ Time Frame: 90 days after randomisation ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ischaemic Stroke
Intervention  ICMJE
  • Drug: 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)
  • Drug: 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).
Study Arms  ICMJE
  • Experimental: Early treatment
    Early treatment of patients with ischaemic stroke related to atrial fibrillation (AF) with direct oral anticoagulations (DOACs).
    Intervention: Drug: Early treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)
  • Late treatment
    Treatment with direct oral anticoagulations (DOACs) according the current standard practice in patients with acute ischemic stroke related to atrial fibrillation (AF).
    Intervention: Drug: Late treatment with Rivaroxaban (Xarelto®), Dabigatran (Pradaxa®), Apixaban (Eliquis®) or Edoxaban (Lixiana®)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 8, 2017)
2000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2021
Estimated Primary Completion Date August 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cecilia Ferrari +41 31 632 31 40 cecilia.ferrari@insel.ch
Contact: Patricia Plattner, MSc patricia.plattner@insel.ch
Listed Location Countries  ICMJE Austria,   Finland,   Germany,   Greece,   Norway,   Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03148457
Other Study ID Numbers  ICMJE 2017-00588
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital Inselspital, Berne
Study Sponsor  ICMJE University Hospital Inselspital, Berne
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Urs Fischer, Prof. MD Dept. of Neurology, Inselspital Bern
PRS Account University Hospital Inselspital, Berne
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP