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

• ClinicalTrials.gov Identifier: NCT04142125
• Recruitment Status: Active, not recruiting
• First Posted: October 29, 2019
• Last Update Posted: September 10, 2022
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Population Health Research Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ischemic Stroke; Intracranial Atherosclerotic Disease	Drug: Rivaroxaban 2.5 Mg Oral Tablet bid; Drug: Acetylsalicyclic acid 81 mg tablet qd	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: investigator-initiated, open-label, blinded endpoint assessment, controlled, randomized pilot trial (PROBE design)
• Masking: Single (Outcomes Assessor)
• Masking Description: Blinded assessment of endpoint
• Primary Purpose: Treatment
• Official Title: Combination Anti-thrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease: Protocol for a Pilot Randomized Trial
• Actual Study Start Date: February 3, 2020
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

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 Name: Xarelto; Drug: Acetylsalicyclic acid 81 mg tablet qd; Pts will receive ASA; Other Name: Aspirin
Active Comparator: Control (ASA alone); Aspirin 81 mg qd	Drug: Acetylsalicyclic acid 81 mg tablet qd; Pts will receive ASA; Other Name: Aspirin

Outcome Measures

Primary Outcome Measures :

1. Recruitment rate [ Time Frame: From randomization to end of recruitment (2 years) ]
   Recruitment rate of potentially eligible patients from neurology clinics
2. Refusal rate [ Time Frame: 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
3. Retention rate [ Time Frame: From randomization to End of Study (median 2 years) ]
   Rate of patients who remain in the clinical trial until EOS or qualifying event
4. Incidence rate of Intracranial hemorrhage [ Time Frame: From randomization to End of Study (median 2 years) ]
   Rate of patients who experience an intracranial hemorrhage during the study

Secondary Outcome Measures :

1. Major hemorrhage [ Time Frame: From randomization to End of Study (median 2 years) ]
   Major hemorrhage as defined by ISTH criteria
2. Combination of ISTH major hemorrhages & clinically-relevant non-major hemorrhages [ Time Frame: From randomization to End of Study (median 2 years) ]
   Major hemorrhage and clinically relevant non-major as per ISTH criteria
3. Recurrent ischemic stroke & MRI-detected incident covert brain infarction [ Time Frame: 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
4. Recurrent ischemic stroke [ Time Frame: From randomization to End of Study (median 2 years) ]
   Recurrent ischemic stroke that is restricted to the area of the qualifying stenosis
5. Composite of stroke, myocardial infarction or vascular death [ Time Frame: From randomization to End of Study (median 2 years) ]
   Composite of stroke, MI or vascular death

Eligibility Criteria

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

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

Contacts and Locations

Locations

Canada, Alberta

Alberta Health Services

Calgary, Alberta, Canada, T2N 2T9

University of Alberta

Edmonton, Alberta, Canada, T6G 2B7

Canada, British Columbia

Vancouver General Hospital

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Ontario

Hamilton Health Sciences

Hamilton, Ontario, Canada, L8L 2X2

Kingston Health Sciences Centre

Kingston, Ontario, Canada, K7L 2V7

London Health Sciences Centre

London, Ontario, Canada, N6A 5A5

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada, K1Y 4E9

Rhema Research Institute

Owen Sound, Ontario, Canada, N4K 6M9

Sunnybrook Health Science Centre

Toronto, Ontario, Canada, M4N 3M5

Toronto Western Hospital

Toronto, Ontario, Canada, M5T 2S8

Sponsors and Collaborators

Population Health Research Institute

Investigators

• Principal Investigator: Kanjana S. Perera, MD, FRCPC; Hamilton Health Sciences Corporation

More Information

• Responsible Party: Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT04142125
• Other Study ID Numbers: CATIS-ICAD
• First Posted: October 29, 2019
• Last Update Posted: September 10, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Population Health Research Institute:

Pilot study; Rivaroxaban; Factor Xa Inhibitors; Intracranial Atherosclerotic Disease

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Rivaroxaban; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Anticoagulants