Rivaroxaban versus Aspirin in secondary prevention of stroke and prevention of systemic embolism in patients with recent embolic stroke of undetermined source (ESUS)
- Conditions
- Embolic stroke of undetermined source (ESUS)MedDRA version: 19.0 Level: PT Classification code 10014498 Term: Embolic stroke System Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2013-000768-27-GB
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 7213
1. Embolic stroke of undetermined source (ESUS) defined as:
• Recent ischemic stroke (including TIA with positive neuroimaging) visualized by brain CT or MRI that is not lacunar (i.e., lacunar infarcts are subcortical infarcts =1.5 cm in the territory of middle cerebral artery or pons; infarcts involving the cerebellum or lateral medulla are not considered as lacunar infarcts). Patients with multiple simultaneous acute lacunar infarcts on DWI imaging may be included. In case of embolic large artery occlusions clearly documented on angiography who undergo successful recanalization, visualization of infarct on neuroimaging is not mandated), and
• Absence of cervical carotid atherosclerotic stenosis (or vertebral and basilar atherosclerotic stenosis in case of posterior circulation stroke), that is > 50%, or occlusion in arteries supplying the area of ischemia in CT or magnetic resonance (MR) angiography or conventional angiography or ultrasound, and
• No history of AF, no documented AF on 12-lead electrocardiogram (ECG) or episode of AF lasting 6 minutes or longer detected after = 24-hour cardiac rhythm monitoring (Holter or telemetry; at least 20 hours acceptable), and
• No intra-cardiac thrombus on either transesophageal or transthoracic echocardiography, and
• No other specific cause of stroke identified by routine clinical care (e.g., arteritis, dissection, migraine/vasospasm, drug abuse)
2 . Time from recent ischemic stroke to randomization and first study medication intake (and only if the investigator regards it as safe to initiate therapy with an anticoagulant) between 7 days and 6 months except:
• in case of minor strokes (NIHSS = 3), study medication may be initiated as early as 3 days after stroke onset.
• in case of intravenous thrombolysis treatment or hemorrhagic transformation seen on the qualifying CT or MRI, study medication will not be initiated before 10 days after the acute stroke event unless a repeat CT or MRI scan performed before randomization documents the absence of no new or extension of hemorrhage.
3. All planned diagnostic tests for stroke evaluation must be completed. Brain imaging and 24-hour cardiac monitoring must be repeated if new symptoms of stroke/TIA occurred after the initial stroke evaluation, as does 24-hour cardiac monitoring if symptoms suggestive of AF occur.
4. Age =50 years
5. For patients with age 50-59 years at least one of the following risk factors: stroke or TIA prior to index stroke (includes covert/silent strokes on neuroimaging), diabetes, hypertension, current tobacco smoker, or heart failure.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4000
1. Severely disabling stroke (modified Rankin score =4 at screening)
2. If imaging of intracranial arteries is performed by CT or MR angiography or transcranial Doppler: > 50% luminal stenosis or occlusion in arteries supplying the area of ischemia
3. Patent foramen ovale with plans for closure
4. Known serious infection or inflammatory disease that may be the cause of stroke
5. Patient has or is intended to receive an implantable ECG loop recorder
6. Indication for chronic anticoagulation based on guideline recommendations or investigator´s judgment; e.g., patient with prosthetic mechanical valve, venous thromboembolism, hypercoagulable state
7. Indication for chronic antiplatelet therapy based on investigator´s judgment, in which anticoagulation is not a reasonable substitute, or chronic therapy with a conventional nonsteroid anti-inflammatory drug (NSAID) for a non-stroke indication
9. Active bleeding, major bleeding within last 6 months, high risk for serious bleeding contraindicating anticoagulant or antiplatelet therapy or history of primary intracranial hemorrhage
10. Hepatic disease associated with coagulopathy (prothrombin time prolonged beyond the normal range) and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C
11. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as assessed at local laboratory within 1 month of screening
14. Female of childbearing potential who are not surgically sterile, or, if sexually active not willing to use adequate contraceptive measures with a failure rate less than 1% per year (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, male partner sterilization) before entry and throughout the study, as well as pregnant or breast feeding women
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method