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

Study Overview
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Brief Summary
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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.

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

Conditions
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Ischemic Stroke, Intracranial Atherosclerotic Disease

Intervention / Treatment
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* Drug: Rivaroxaban 2.5 Mg Oral Tablet bid
* Drug: Acetylsalicyclic acid 81 mg tablet qd


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 40 years 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: a high-risk TIA defined as TIA with motor and/or speech involvement or an ischemic stroke Written informed consent consistent with local regulations governing research in human subjects Exclusion Criteria: Indication for DAPT for > 90 days on guideline recommendations or investigator ́s judgment; e.g., cardiac stenting. Indication for chronic anticoagulation based on guideline recommendations or investigator ́s judgment; e.g. patient with prosthetic mechanical valve, venous thromboembolism, hypercoagulable state Atrial fibrillation or a history of atrial fibrillation Intracranial arterial occlusion (e.g. 100% stenosis) responsible for the acute brain ischemia Intracranial arterial stenosis secondary to causes other than atherosclerosis Extracranial carotid artery disease ipsilateral to the qualifying brain ischemia with a plan for carotid revascularization Intraluminal thrombus Subdural hematoma within 12 months of randomization Previous spontaneous hemorrhagic stroke (e.g. intracerebral or subarachnoid hemorrhage) Traumatic brain hemorrhage within 1 month of randomization Contraindication for MRI scan (e.g. pacemaker incompatible with MRI) Advanced kidney disease (recent estimated GFR <30 ml per minute) Modified Rankin Scale (mRS) >=4 at entry Platelet count less than 100,000/mm3 at enrolment or other bleeding diathesis Uncontrollable hypertension with systolic BP/ diastolic BP consistently above180/100mmHg after treatment Known hypersensitivity to either ASA or rivaroxaban Life expectancy less than 6 months 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 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 Inability to adhere to study procedures 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) Previous randomization to this study or participating in a study with an investigational drug or medical device at the time of randomization Antiphospholipid antibody syndrome

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: investigator-initiated, open-label, blinded endpoint assessment, controlled, randomized pilot trial (PROBE design)
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pilot study, Rivaroxaban, Factor Xa Inhibitors, Intracranial Atherosclerotic Disease