Intracranial Atherosclerotic Disease, Ischemic Stroke
Conditions
Keywords
Pilot study, Rivaroxaban, Factor Xa Inhibitors, Intracranial Atherosclerotic Disease
Brief summary
CATIS-ICAD is a clinical pilot study in which patients who have had a recent ischemic stroke, that is a stroke caused by a blood clot or a narrowing of the blood vessels in the brain due to the build up of plaque, will be randomly assigned to receive either low-dose rivaroxaban + aspirin or aspirin alone.
Interventions
DRUGRivaroxaban 2.5 Mg Oral Tablet bid
Pts will receive rivaroxaban + aspirin
DRUGAcetylsalicyclic acid 81 mg tablet qd
Pts will receive ASA
Sponsors
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinded assessment of endpoint
Intervention model description
investigator-initiated, open-label, blinded endpoint assessment, controlled, randomized pilot trial (PROBE design)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 40 years 2. Recent brain ischemia attributed to intracranial atherosclerotic stenosis of 30-99% as evidenced by CT or MR angiography, occurring between 7 to 100 days prior to randomization and consisting of either: 1. a high-risk TIA defined as TIA with motor and/or speech involvement or 2. an ischemic stroke 3. Written informed consent consistent with local regulations governing research in human subjects
Exclusion criteria
1. Indication for DAPT for \> 90 days on guideline recommendations or investigator ́s judgment; e.g., cardiac stenting. 2. Indication for chronic anticoagulation based on guideline recommendations or investigator ́s judgment; e.g. patient with prosthetic mechanical valve, venous thromboembolism, hypercoagulable state 3. Atrial fibrillation or a history of atrial fibrillation 4. Intracranial arterial occlusion (e.g. 100% stenosis) responsible for the acute brain ischemia 5. Intracranial arterial stenosis secondary to causes other than atherosclerosis 6. Extracranial carotid artery disease ipsilateral to the qualifying brain ischemia with a plan for carotid revascularization 7. Intraluminal thrombus 8. Subdural hematoma within 12 months of randomization 9. Previous spontaneous hemorrhagic stroke (e.g. intracerebral or subarachnoid hemorrhage) 10. Traumatic brain hemorrhage within 1 month of randomization 11. Contraindication for MRI scan (e.g. pacemaker incompatible with MRI) 12. Advanced kidney disease (recent estimated GFR \<30 ml per minute) 13. Modified Rankin Scale (mRS) \>=4 at entry 14. Platelet count less than 100,000/mm3 at enrolment or other bleeding diathesis 15. Uncontrollable hypertension with systolic BP/ diastolic BP consistently above180/100mmHg after treatment 16. Known hypersensitivity to either ASA or rivaroxaban 17. Life expectancy less than 6 months 18. Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e., human immunodeficiency virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, or posaconazole, if used systemically 19. 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 20. Inability to adhere to study procedures 21. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g., employee or student of the investigational site) 22. Previous randomization to this study or participating in a study with an investigational drug or medical device at the time of randomization 23. Antiphospholipid antibody syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Refusal rate | From randomization to end of recruitment (2 years) | Rate of patients who refuse to participate in the clinical trial who otherwise are eligible for the study |
| Recruitment rate | From randomization to end of recruitment (2 years) | Recruitment rate of potentially eligible patients from neurology clinics |
| Retention rate | From randomization to End of Study (median 2 years) | Rate of patients who remain in the clinical trial until EOS or qualifying event |
| Incidence rate of Intracranial hemorrhage | From randomization to End of Study (median 2 years) | Rate of patients who experience an intracranial hemorrhage during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major hemorrhage | From randomization to End of Study (median 2 years) | Major hemorrhage as defined by ISTH criteria |
| Composite of stroke, myocardial infarction or vascular death | From randomization to End of Study (median 2 years) | Composite of stroke, MI or vascular death |
| Combination of ISTH major hemorrhages & clinically-relevant non-major hemorrhages | From randomization to End of Study (median 2 years) | Major hemorrhage and clinically relevant non-major as per ISTH criteria |
| Recurrent ischemic stroke & MRI-detected incident covert brain infarction | From randomization to End of Study (median 2 years) | Symptomatic investigator reported ischemic stroke and MRI detected covert brain infarct as determined by MRI corelab reading baseline and end of study MRI |
| Recurrent ischemic stroke | From randomization to End of Study (median 2 years) | Recurrent ischemic stroke that is restricted to the area of the qualifying stenosis |
Countries
Canada
Outcome results
None listed