Atrial Fibrillation, Ischemic Stroke
Conditions
Keywords
Oral anticoagulants (NOAC)
Brief summary
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
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.
Interventions
OTHEREarly start of NOAC
Initiation of NOAC up until day 4 after acute ischemic stroke in patients with atrial fibrillation
OTHERLate start of NOAC
Initiation of NOAC between day 5 and day 10 after acute ischemic stroke in patients with atrial fibrillation
Sponsors
The Swedish Stroke Register (Riksstroke)
Uppsala University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality | 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrent acute ischemic stroke | 90 days | 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 |
| Symptomatic intracerebral hemorrhage (S-ICH) | 90 days | 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 |
| All-cause mortality | 90 days | — |
| Functional outcome | 90 days | Defined by grade on the modified Rankin Scale (mRS) |
| Major hemorrhages | 90 days | 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 |
Countries
Sweden
Outcome results
None listed