Please select the eligibility criteria that correspond to the clinical trial below.
Title: OPtimal TIMing of Anticoagulation After Acute Ischaemic Stroke: a Randomised Controlled Trial
Brief Summary: OPTIMAS is a large, prospective, partially blinded randomised controlled trial of early (within ≤4 days \[96hrs\]) or standard (between day 7 and day 14 after stroke onset) initiation of anticoagulation after stroke in patients with atrial fibrillation (AF), using any licensed dose of a direct oral anticoagulant (DOAC). The trial will use a non-inferiority gatekeeper approach to test for non-inferiority of early anticoagulation followed by a test for superiority, if non-inferiority is established.


Options:
A: Inclusion Criteria:

1. Aged 18 years or over
2. Clinical diagnosis of acute ischaemic stroke
3. AF, confirmed by any of:

   1. 12-lead ECG recording
   2. Inpatient ECG telemetry
   3. Other prolonged ECG monitoring technique (e.g. Holter monitor)
   4. Known diagnosis of atrial fibrillation verified by medical records (e.g. primary care records, letter from secondary care)
4. Eligibility to commence DOAC in accordance with approved prescribing recommendations confirmed by treating physician
5. Uncertainty on the part of the treating physician regarding early versus standard initiation of DOAC.

Exclusion Criteria:

1. Contraindication to anticoagulation:

   1. Coagulopathy or current or recent anticoagulation with vitamin K antagonist (VKA) leading to INR ≥1.7 at randomisation.
   2. Thrombocytopenia (platelets \< 75 x 10⁹/L)
   3. Other coagulopathy or bleeding tendency (based on clinical history or laboratory parameters) judged to contraindicate anticoagulation by treating clinician
2. Contraindication to early anticoagulation

   1. Known presence of haemorrhagic transformation with parenchymal haematoma occupying \>30% of the infarct volume and exerting significant mass effect (i.e. PH2) (NB: HI1, HI2 and PH1 are not considered contraindications)
   2. Presence of clinically significant intracranial haemorrhage unrelated to qualifying infarct
   3. Any other contraindication to early anticoagulation as judged by the treating clinician
3. Contraindication to use of DOAC:

   1. Known allergy or intolerance to both Factor Xa inhibitor and direct thrombin inhibitor
   2. Definite indication for VKA treatment e.g. mechanical heart valve, valvular AF, antiphospholipid syndrome
   3. Severe renal impairment with creatinine clearance (Cockcroft \& Gault formula) \<15 mL/min (i.e. 14 mL/min or less)
   4. Liver function tests ALT \> 2x ULN
   5. Cirrhotic patients with Child Pugh score equating to grade B or C
   6. Patient is taking medication with significant interaction with DOAC, including:

      * Azole antifungals (e.g. ketoconazole, itraconazole)
      * HIV protease inhibitors (e.g. ritonavir)
      * Strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John's Wort)
      * Dronedarone
4. Pregnant or breastfeeding women
5. Presence on acute brain imaging of non-stroke pathology judged likely to explain clinical presentation (e.g. mass lesion, encephalitis)
6. Inability for patient to be followed up within 90 days of trial entry
7. Patient or representative refusal to consent to study procedures, including the site informing GP and healthcare professional responsible for anticoagulation care of participants
8. Any other reason that the PI considers would make the patient unsuitable to enter OPTIMAS.

Note that current DOAC treatment is NOT an exclusion criterion, as long as the treating physician considers it appropriate to restart (or continue) according to the timings specified in the OPTIMAS trial protocol. Continuation of the DOAC would be recorded as a start time of zero hours.
B: Inclusion Criteria:

* Males and females ≥ 18 yrs with atrial fibrillation (AF) and one or more of the following risk factors for stroke:
* Age ≥ 75, previous stroke
* transient ischemic attack (TIA) or Systemic Embolism (SE)
* Symptomatic congestive heart failure or left ventricular dysfunction with left ventricular ejection fraction (LVEF) ≤ 40%
* Diabetes mellitus or hypertension requiring pharmacological treatment
C: Inclusion Criteria:

* 21 years of age or older; male or female.
* Able to provide written informed consent.
* History of documented AF within the prior 12 months
* A moderate to high risk of stroke, as defined by CHADS2 index score of at least 2

Exclusion Criteria:

* Transient atrial fibrillation secondary to other reversible disorders
* Subjects with moderate or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve
* Subjects with any contraindication for anticoagulant agents;
* Subjects with conditions associated with high risk of bleeding or have known or suspected hereditary or acquired bleeding disorders
* Females of childbearing potential including the following:

  * Females with a history of tubal-ligation
  * Females less than 2 years post-menopausal
D: Inclusion Criteria:

* Patients with Nonvalvular Atrial Fibrillation (NVAF) aged 80 years or older who are ineligible for available oral anticoagulation therapy

Exclusion Criteria:

* Patients with active bleeding
* Patients who have poorly controlled hypertension
* Patients who have liver dysfunction accompanied with disorder of blood coagulation

Answer: A