Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Double Blind, Factorial Design, Phase IV Trial to Compare the Efficacy and Safety of Cilostazol Long-term Treatment With Aspirin in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage for the Prevention of Cerebral Hemorrhage and Cardiovascular Events and to Compare the Preventive Effect of Probucol in the Same Patient Group With Non-drug User Group for the Prevention of Cardiovascular Events
Brief Summary: Through this study, the investigators are to prove that Cilostazol effectively prevent cardiovascular events in ischemic stroke patients with high risk of cerebral hemorrhage, along with no significant increase in the risk of occurrence of hemorrhagic side effects.

The primary hypothesis of this study is; Cilostazol alone or with probucol will reduce the risk of cerebral hemorrhage without increase of cardiovascular events compared to aspirin in the ischemic stroke patients with symptomatic or asymptomatic old cerebral hemorrhage.

This study will prove the superiority of cilostazol on the prevention of cerebral hemorrhagic events without increasing the cardiovascular events against aspirin and the superiority of probucol on the prevention of overall cardiovascular events.


Options:
A: Inclusion criteria

* Adult (older than 18 years old, no upper age limit)
* with a history of paroxysmal, persistent or long-standing non-valvular atrial fibrillation (documented on an electrocardiogram)
* and a CHA2DS2VASc score of 2 or more who have an indication for long-term anticoagulation
* who suffered from a spontaneous intracerebral haemorrhage (while being treated with oral anticoagulants or not) documented with brain CT or MRI
* more than 14 days before randomization (no upper delay limit)
* for whom there is a clinical equipoise regarding the choice of the best preventive strategy to avoid future vascular events.

Exclusion criteria for all treatment groups

* Pre-randomisation modified Rankin score of 4 or 5
* Conditions other than atrial fibrillation for which the patient requires long term anticoagulation (for example prosthetic mechanical heart valve)
* Serious bleeding events within the 6 months before randomisation (except for intracerebral haemorrhage)
* Life expectancy of less than 1 year
* Pregnancy or breastfeeding

Exclusion criteria related to the LAAC only

* Contraindications due to local, anatomical reasons (such as thrombus in the left atrial appendage, infection with a risk of endocarditis)
* Patients older than 85 years
* CHA2DS2VASc score of 2 or 3
* Patient or attending physician are unwilling to undergo/perform intervention for LAAC

Exclusion criteria related to the Direct OAC only

* Chronic renal insufficiency (clearance of creatinine by Cockcroft method \< 30ml/min)
* Body weight lower than 50 kg
* Allergy to apixaban
* Coexisting conditions predisposing to head trauma (e.g. gait disturbances, uncontrolled seizures disorders)
* Patient or attending physician are unwilling to use of Direct OAC
B: Inclusion Criteria:

* Patients with transient ischemic attack (TIA) or ischemic stroke within 180 days prior to screening - Adult aged 20 years or older
* High risk of hemorrhagic stroke (history of intracranial hemorrhage or imaging evidence of previous intracranial hemorrhage)
* Informed consent

Exclusion Criteria:

* Clinical diagnosis of myocardial infarction or coronary intervention within 4 weeks
* Bleeding tendency
* Pregnant or breast-feeding woman
* Hemorrhagic stroke within 6 months
* Patient who was taking antithrombotic medication other than aspirin and does not agree to change the previous medication
* Severe cardiovascular disease such as cardiomyopathy or congestive heart failure
* Life expectancy less than one year
* Contraindication to long term aspirin use
* Enrolled in other clinical trial within 30 days
C: Inclusion Criteria:

1. history of significant bleeding (i.e. bleeding which required intervention or hospitalization), even in the absence of anticoagulation treatment at the time of the bleeding event, or
2. a cardioembolic event, which occurred on anticoagulation, or
3. a high risk profile of the patient, defined as a CHA2DS2-VASc score ≥ 3 and a HAS-BLED score ≥ 2

Exclusion Criteria:

1. thrombus in the LA or LAA;
2. mechanical valve prosthesis;
3. mitral stenosis;
4. previous LAA ligation during cardiac surgery;
5. life expectancy less than 2 years;
6. comorbidities other than AF, which present an indication for anticoagulation;
7. patent foramen ovale with atrial septal aneurysm
8. mobile plaque in the aorta;
9. symptomatic atherosclerosis of the carotid artery;
10. pericardial effusion greater than 10 mm;
11. clinically significant bleeding within the 30 days prior to the scheduled procedure;
12. stroke or other cardioembolic event within the 30 days prior to the scheduled procedure;
13. acute coronary syndrome within the 90 days prior to the scheduled procedure,
14. gravidity,
15. significant valvular disease,
16. creatinine clearance less than 30 ml/min
D: Inclusion Criteria:

1. Adults (≥30 years) with spontaneous primary ICH (i.e. without known underlying structural, macrovascular or other cause (e.g. arteriovenous malformation, tumour) after adequate investigation at the discretion of the local investigator). This will include participants presumed to have cerebral SVD (both hypertensive arteriopathy and cerebral amyloid angiopathy)
2. Clinical team opinion that BP control since the ICH is not adequate AND the measured SBP prior to randomisation is ≥130 mm Hg
3. There is no time limit for recruitment; however, recruitment as soon as is practical after the ICH is encouraged. Recruitment at a later stage is acceptable as long as there is evidence of inadequate BP control AND SBP at randomisation is ≥130 mm Hg
4. Ability and willingness to undertake BP measurements,, either unassisted or with the help of a relative, friend or carer: this can be undertaken in any destination after hospital discharge (e.g. home, rehabilitation unit, nursing or care home)
5. Ability and willingness to attend and complete the study assessments including cognitive screen
6. Ability and willingness to provide informed consent, or with a suitable consultee available and able to participate in the intervention (e.g. with a motivated carer)

Exclusion Criteria:

1. Inability to provide informed consent or lack of suitable consultee (if unable to provide personal consent, lack of suitable consultee)
2. Evidence of a macrovascular or structural cause for ICH (e.g. AVM or tumour)
3. Diagnosis of dementia (DSM IV criteria, or self-reported or documented in medical records)
4. Low Functional status (MRS ≥4) before or after ICH or frailty likely to make participation in 1-year follow-up difficult for the participant
5. Life expectancy \<2 years
6. Taking more than 2 BP-lowering medications (i.e. 3 or more) at the time of consent
7. Consistently good BP control (below 130/80 mm Hg on measures taken as part of routine clinical care) prior to planned recruitment, judged not to require more intensive treatment
8. Known flow-restricting intracranial/extracranial large arterial stenosis
9. Known absence of mobile phone coverage from all network operators and home internet at the participant's home
10. Known sensitivity or contra-indication to BP treatments (e.g. symptomatic postural hypotension) is not an absolute exclusion criterion, but more information must be provided
11. Note that participation in other CTIMP or device trial is NOT an automatic exclusion criterion

Answer: B