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

Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04142125
• Other study ID #: CATIS-ICAD
• Status: Completed
• Phase: Phase 3
• Start date: February 3, 2020
• Est. completion date: September 18, 2023

Study information

• Verified date: September 2023
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: September 18, 2023
• Est. primary completion date: September 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Infarction
• Intracranial Atherosclerotic Disease
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Rivaroxaban 2.5 Mg Oral Tablet bid
Pts will receive rivaroxaban + aspirin
• Acetylsalicyclic acid 81 mg tablet qd
Pts will receive ASA

Locations

Country	Name	City	State
Canada	Alberta Health Services	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Rhema Research Institute	Owen Sound	Ontario
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment rate	Recruitment rate of potentially eligible patients from neurology clinics	From randomization to end of recruitment (2 years)
Primary	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)
Primary	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)
Primary	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	Major hemorrhage	Major hemorrhage as defined by ISTH criteria	From randomization to End of Study (median 2 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Composite of stroke, myocardial infarction or vascular death	Composite of stroke, MI or vascular death	From randomization to End of Study (median 2 years)