Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease

Phase 3

Completed

• Conditions: Ischemic Stroke; Intracranial Atherosclerotic Disease
• Interventions: Drug: Rivaroxaban 2.5 Mg Oral Tablet bid; Drug: Acetylsalicyclic acid 81 mg tablet qd

• Registration Number: NCT04142125
• Lead Sponsor: Population Health Research Institute

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-25
• Study First Submitted QC: 2019-10-25
• Study First Posted: 2019-10-29
• Study Start: 2020-02-03
• Status Verified: 2023-09
• Primary Completion: 2023-09-18
• Study Completion: 2023-09-18
• Last Update Submitted: 2023-09-24
• Last Update Posted: 2023-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental (riva + ASA)	Rivaroxaban 2.5 Mg Oral Tablet bid	Rivaroxaban 2.5mg bid + aspirin 81mg qd
Experimental (riva + ASA)	Acetylsalicyclic acid 81 mg tablet qd	Rivaroxaban 2.5mg bid + aspirin 81mg qd
Control (ASA alone)	Acetylsalicyclic acid 81 mg tablet qd	Aspirin 81 mg qd

Primary Outcome Measures

Name	Time	Method
Recruitment rate	From randomization to end of recruitment (2 years)	Recruitment rate of potentially eligible patients from neurology clinics
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
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 Outcome Measures

Name	Time	Method
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
Composite of stroke, myocardial infarction or vascular death	From randomization to End of Study (median 2 years)	Composite of stroke, MI or vascular death
Major hemorrhage	From randomization to End of Study (median 2 years)	Major hemorrhage as defined by ISTH criteria
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

Trial Locations

Locations (10)

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada

Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada

Alberta Health Services; 🇨🇦 Calgary, Alberta, Canada

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Rhema Research Institute; 🇨🇦 Owen Sound, Ontario, Canada

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada