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

Combination Anti-thrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease: Protocol for a Pilot Randomized Trial

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; Intracranial Atherosclerotic Disease
• Intervention / Treatment: Drug: Rivaroxaban 2.5 Mg Oral Tablet bid; Drug: Acetylsalicyclic acid 81 mg tablet qd

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Alberta Health services
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
    • Owen Sound, Ontario, Canada, N4K 6M9
      • Rhema Research Institute
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Science Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental (riva + ASA); Rivaroxaban 2.5mg bid + aspirin 81mg qd	Drug: Rivaroxaban 2.5 Mg Oral Tablet bid; Pts will receive rivaroxaban + aspirin; Other Names: Xarelto; Drug: Acetylsalicyclic acid 81 mg tablet qd; Pts will receive ASA; Other Names: Aspirin
Active Comparator: Control (ASA alone); Aspirin 81 mg qd	Drug: Acetylsalicyclic acid 81 mg tablet qd; Pts will receive ASA; Other Names: Aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Recruitment rate of potentially eligible patients from neurology clinics	From randomization to end of recruitment (2 years)
Refusal rate	Rate of patients who refuse to participate in the clinical trial who otherwise are eligible for the study	From randomization to end of recruitment (2 years)
Retention rate	Rate of patients who remain in the clinical trial until EOS or qualifying event	From randomization to End of Study (median 2 years)
Incidence rate of Intracranial hemorrhage	Rate of patients who experience an intracranial hemorrhage during the study	From randomization to End of Study (median 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major hemorrhage	Major hemorrhage as defined by ISTH criteria	From randomization to End of Study (median 2 years)
Combination of ISTH major hemorrhages & clinically-relevant non-major hemorrhages	Major hemorrhage and clinically relevant non-major as per ISTH criteria	From randomization to End of Study (median 2 years)
Recurrent ischemic stroke & MRI-detected incident covert brain infarction	Symptomatic investigator reported ischemic stroke and MRI detected covert brain infarct as determined by MRI corelab reading baseline and end of study MRI	From randomization to End of Study (median 2 years)
Recurrent ischemic stroke	Recurrent ischemic stroke that is restricted to the area of the qualifying stenosis	From randomization to End of Study (median 2 years)
Composite of stroke, myocardial infarction or vascular death	Composite of stroke, MI or vascular death	From randomization to End of Study (median 2 years)

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Kanjana S. Perera, MD, FRCPC, Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Actual): September 18, 2023
• Study Completion (Actual): September 18, 2023

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 25, 2019
• First Posted (Actual): October 29, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Rivaroxaban; Pilot study; Factor Xa Inhibitors; Intracranial Atherosclerotic Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: CATIS-ICAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No