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

Uppsala University888 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

888

Conditions

Ischemic Stroke Atrial Fibrillation

Interventions

Early start of NOACOTHER

Initiation of NOAC up until day 4 after acute ischemic stroke in patients with atrial fibrillation

Late start of NOACOTHER

Initiation of NOAC between day 5 and day 10 after acute ischemic stroke in patients with atrial fibrillation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (36)

Outcomes

Primary Outcomes

Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality

Time frame: 90 days

Secondary Outcomes

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

Time frame: 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

Time frame: 90 days

All-cause mortality

Time frame: 90 days

Functional outcome

Defined by grade on the modified Rankin Scale (mRS)

Time frame: 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

Time frame: 90 days

Data from ClinicalTrials.gov

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