Clinical trial NCT04142125: Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease
Official title: Combination Anti-thrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease: Protocol for a Pilot Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke
Intracranial Atherosclerotic Disease
Keywords: Pilot study
Rivaroxaban
Factor Xa Inhibitors
Intracranial Atherosclerotic Disease
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2019-10-29
Enrollment: 101
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: investigator-initiated, open-label, blinded endpoint assessment, controlled, randomized pilot trial (PROBE design)
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Recruitment rate
timeFrame: From randomization to end of recruitment (2 years)
measure: Refusal rate
timeFrame: From randomization to end of recruitment (2 years)
measure: Retention rate
timeFrame: From randomization to End of Study (median 2 years)
measure: Incidence rate of Intracranial hemorrhage
timeFrame: From randomization to End of Study (median 2 years)
Secondary outcomes:
measure: Major hemorrhage
timeFrame: From randomization to End of Study (median 2 years)
measure: Combination of ISTH major hemorrhages & clinically-relevant non-major hemorrhages
timeFrame: From randomization to End of Study (median 2 years)
measure: Recurrent ischemic stroke & MRI-detected incident covert brain infarction
timeFrame: From randomization to End of Study (median 2 years)
measure: Recurrent ischemic stroke
timeFrame: From randomization to End of Study (median 2 years)
measure: Composite of stroke, myocardial infarction or vascular death
timeFrame: From randomization to End of Study (median 2 years)
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Alberta Health Services
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Owen Sound
country: Canada
facility: Rhema Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Kanjana S. Perera, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: