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

• ClinicalTrials.gov Identifier: NCT04142125
• Recruitment Status: Recruiting
• First Posted: October 29, 2019
• Last Update Posted: February 8, 2021
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Population Health Research Institute

Tracking Information

• First Submitted Date: October 25, 2019
• First Posted Date: October 29, 2019
• Last Update Posted Date: February 8, 2021
• Actual Study Start Date: February 3, 2020
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2019)

• Recruitment rate [ Time Frame: From randomization to end of recruitment (2 years) ]
  Recruitment rate of potentially eligible patients from neurology clinics
• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 25, 2019)

• Major hemorrhage [ Time Frame: 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 [ Time Frame: 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 [ 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
• 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
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

Condition

• Ischemic Stroke
• Intracranial Atherosclerotic Disease

Intervention

• 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

Study Arms

• Experimental: Experimental (riva + ASA)
  Rivaroxaban 2.5mg bid + aspirin 81mg qd
  Interventions:

  • Drug: Rivaroxaban 2.5 Mg Oral Tablet bid
  • Drug: Acetylsalicyclic acid 81 mg tablet qd
• Active Comparator: Control (ASA alone)
  Aspirin 81 mg qd
  Intervention: Drug: Acetylsalicyclic acid 81 mg tablet qd

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 25, 2019): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amanda Taylor; 905.527.4322 ext 40508; CATIS-ICAD@phri.ca

Contact: Anna Cheng; 905.527.4322 ext 41089; CATIS-ICAD@phri.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT04142125
• Other Study ID Numbers: CATIS-ICAD
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Population Health Research Institute
• Study Sponsor: Population Health Research Institute
• Collaborators: Not Provided

Investigators

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

• PRS Account: Population Health Research Institute
• Verification Date: February 2021