TIMING of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation

Study Overview
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Brief Summary
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This study will compare early with late start of treatment with Non-vitamin K oral anticoagulation (NOAC) in adult patients with acute ischemic stroke and atrial fibrillation; it is a registry-based randomized clinical trial (R-RCT) using The Swedish Stroke Register (Riksstroke). Half of the patients will start NOAC early (within 4 days after stroke onset) while the other half will start late (5-10 days after stroke onset).

Detailed Description
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Oral anticoagulation therapy is well established and highly recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation, but the optimal time point to start after an acute ischemic stroke is not known. The intervention in this study will be timing of treatment onset. The choice of NOAC (i.e. apixaban, dabigatran, edoxaban or rivaroxaban) after the acute ischemic stroke is at the discretion of the treating physician. This study will use the Swedish Stroke Register for enrolment, randomization and follow-up, with additional data linkage from other mandatory national registers. Primary outcome will be assessed at 90 days and secondary outcomes (including all-cause mortality and health economic analyses) and will be assessed at 90 days and up to one year after the index ischemic stroke.

Official Title
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Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation: a Prospective Multicenter Registry-based Non-inferiority Randomized Controlled Clinical Trial

Conditions
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Ischemic Stroke, Atrial Fibrillation

Intervention / Treatment
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* Other: Early start of NOAC
* Other: Late start of NOAC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (≥ 18 years) with acute ischemic stroke and atrial fibrillation Eligible and willing to start (or re-start) NOAC Registered in The Swedish Stroke Register Signed informed consent Exclusion Criteria: Contraindication to NOAC (e.g. ongoing bleeding, mechanical heart valve prosthesis) Ongoing therapy with NOAC (without ≥2 days interruption at index stroke) International normalized ratio (INR)>1.7 No second brain imaging (CT/MRI) after thrombolysis/thrombectomy Previous randomization in the TIMING study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early start of NOAC<br>Day 1 to day 4 after ischemic stroke onset | Other: Early start of NOAC<br>* Initiation of NOAC up until day 4 after acute ischemic stroke in patients with atrial fibrillation<br>|
| Active Comparator: Late start of NOAC<br>Day 5 to day 10 after ischemic stroke onset | Other: Late start of NOAC<br>* Initiation of NOAC between day 5 and day 10 after acute ischemic stroke in patients with atrial fibrillation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent acute ischemic stroke | Defined as a new focal neurological deficit of sudden onset lasting at least 24 h (or <24 h if following therapeutic intervention, i.e. thrombolysis or thrombectomy, or if the deficit results in death < 24 h), occurring >24 hours after the index ischemic stroke, irrespective of vascular territory and that is not attributable to edema, brain shift, hemorrhagic transformation, intercurrent illness, hypoxia, or drug toxicity | 90 days | 
| Symptomatic intracerebral hemorrhage (S-ICH) | Defined as a new focal neurological deficit of sudden onset lasting at least 24 h with documented intracerebral hemorrhage (ICH) on imaging (computed tomography (CT) or magnetic resonance imaging (MRI)). Any intraparenchymal hematoma (≥10mm) will be considered, including hemorrhagic transformation of the index ischemic stroke. However microhemorrhages (<10mm) are not considered to be an ICH. ICH will be classified as symptomatic if it is associated with ≥4 points in total NIHSS or ≥2 points in one NIHSS category | 90 days | 
| All-cause mortality |  | 90 days | 
| Functional outcome | Defined by grade on the modified Rankin Scale (mRS) | 90 days | 
| Major hemorrhages | Defined as bleedings that are fatal or life-threatening (according to the definition by the International Society on Thrombosis and Haemostasis) or lead to hospitalization | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral anticoagulants (NOAC)