Please select the eligibility criteria that correspond to the clinical trial below.
Title: Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation: a Prospective Multicenter Registry-based Non-inferiority Randomized Controlled Clinical Trial
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).


Options:
A: Inclusion Criteria: All of below

* Acute ischemic stroke or TIA presumed to be cardioembolic origin (within 5 days from stroke onset) with mild severity: infarct size on DWI less than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
* Atrial fibrillation including paroxysmal atrial fibrillation: atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary).
* Age ≥19 years
* Informed consent

Exclusion Criteria: Any of below

* Chronic renal failure (GFR less than 30ml/min) or severe hepatic impairment
* Significant hemorrhagic transformation (parenchymal hematoma type I or II by the ECASS definition)
* Stroke mechanism of presumed small vessel occlusion: single small subcortical infarct in the perforating artery territory
* Large hemispheric or cerebellar infarction; larger than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
* Mechanical valve requiring warfarin therapy
* Active internal bleeding
* Prior history of symptomatic intracranial bleeding

  : patients with asymptomatic bleedings or microbleedings on MRI are eligible for inclusion
* Major surgery or major trauma within 30 days that might be associated with increased bleeding risk
* Clinically significant gastrointestinal bleeding within 6 months
* Intravenous tissue plasminogen activator use or mechanical embolectomy within 48 hours plus 'significant hemorrhagic transformation as described above (exclusion criteria 2)' or 'large hemispheric infarction or cerebellar infarction as described above (exclusion criteria 4)'

  : patients achieving successful reperfusion without hemorrhage nor large infarction are eligible for enrollment
* Severe anemia: hemoglobin \<10 g/dL
* Bleeding diathesis; thrombocytopenia (\<90,000/µL, prolonged PT (INR\>1.7)
* Sustained uncontrolled hypertension: SBP \>180 mmHg or DBP \>100 mmHg
* Severe devastating illness, such terminal cancer, hepatic failure; therefore, the participants have a life expectancy less than 6 months.
* Planned invasive procedure with potential for uncontrolled bleeding, including major surgery
B: Inclusion criteria:

* Written informed consent in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations
* Confirmed diagnosis of Cerebral Venous or dural sinus thrombosis (CVT), with or without intracranial haemorrhage
* Completion of anticoagulation therapy for 5-15 days which has been administered until randomisation; anticoagulation must include full-dose low molecular weight heparin or unfractionated heparin
* Eligibility for treatment with an oral anticoagulant
* Further inclusion criteria apply

Exclusion criteria:

* Cerebral Venous or dural sinus thrombosis (CVT) associated with central nervous system infection or due to head trauma
* Planned surgical treatment for CVT
* Conditions associated with increased risk of bleeding
* History of symptomatic non-traumatic intracranial haemorrhage with risk of recurrence according to Investigator judgment
* Treatment with an antithrombotic regimen for an indication other than CVT and requiring continuation of that treatment for the original diagnosis without change in the regimen
* Severe renal impairment
* Active liver disease
* Pregnancy, nursing or planning to become pregnant while in the trial
* Further exclusion criteria apply
C: 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
D: Inclusion Criteria:

Patients of both sexes aged ≥ 18 years with the following 4 inclusion criteria:

* One of the 3 following ischemic events in the preceding 6 months:

  * Transient ischemic attack (TIA)
  * Non-disabling brain infarcts:

    * Inclusion within 6 months after onset
    * Duration of symptoms and signs greater than 24 hours
    * Neurological signs at the time of randomization with a Rankin Scale grade 3 or less
    * With normal computed tomography (CT) scan or CT scan showing a brain infarct (even hemorrhagic infarct)
  * Peripheral embolism
* Atherosclerotic plaque in the thoracic aorta is defined as wall thickness ≥ 4 mm where the protruding material is the largest, measured at transesophageal echocardiography with multiplane transducer or a plaque less than 4 mm but with mobile component.
* Informed consent signed
* Life expectancy \> 3 years

Exclusion Criteria:

* Other causes of embolism:

  * Cardiac: endocarditis, atrial fibrillation, intra-cardiac thrombus, valvular prosthesis, rheumatic valvulopathy, left ventricular aneurysm, or ejection fraction less than 25%
  * Atherosclerotic stenosis ipsilateral to the embolic territory: internal carotid artery stenosis greater than 70%, or severe (judgment of the investigator) intracranial stenosis, or scheduled carotid endarterectomy (in that case inclusion is possible 30 days after the procedure)
  * Uncommon causes: dissection, vasculitis, procoagulant state, or sickle cell disease
* Other exclusion criteria:

  * Intercurrent illness with life expectancy less than 36 months
  * Pregnancy and non-menopausal women
  * Unwillingness to participate
  * Poor medication compliance expected
  * Toxicomania
  * Absolute indication for anticoagulant therapy (e.g. atrial fibrillation, intracardiac thrombus, prosthetic valve)
  * Scheduled for carotid endarterectomy (randomization is possible 30 days after endarterectomy)
* CT scan with an intracranial lesion other than brain infarction (space occupying mass, intracranial hemorrhage)
* Transesophageal echocardiography (TEE) with plaque ≥ 4 mm in thickness distal to the supposed embolized artery (judgement of the investigator).
* Contraindication to clopidogrel, aspirin, and oral anticoagulants

Answer: C