Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)

Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)

The primary goal of the trial is to determine if the experimental arms (rivaroxaban or ticagrelor or both) are superior to the clopidogrel arm for lowering the 1-year rate of ischemic stroke, intracerebral hemorrhage, or vascular death.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Intracranial Arteriosclerosis
• Intervention / Treatment: Drug: Ticagrelor + Aspirin; Other: Risk Factor Management; Drug: Clopidogrel + Aspirin; Drug: Rivaroxaban + Aspirin

Detailed Description

The proposed study is relevant to public health because narrowing of brain arteries is one of the most common causes of stroke worldwide. Compelling evidence suggests novel antithrombotic medications could reduce the rate of stroke in patients with narrowed brain arteries. The proposed study will directly compare novel antithrombotic medications to standard care antiplatelet medications for preventing stroke and death from vascular causes in patients with narrowed brain arteries.

• Study Type: Interventional
• Enrollment (Estimated): 1683
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
    • Mobile, Alabama, United States, 36604
      • University of South Alabama University Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • California
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Chula Vista, California, United States, 91910
      • The Neuron Clinic - Chula Vista
    • Fontana, California, United States, 92335
      • Kaiser Permanente Fontana Medical Center
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Los Alamitos, California, United States, 90720
      • Los Alamitos Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center, Los Angeles, CA
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Salinas, California, United States, 93901
      • Salinas Valley Memorial Hospital
    • San Diego, California, United States, 92103
      • UCSD Medical Center - Hillcrest Hospital
    • Torrance, California, United States, 90503
      • Providence Little Company of Mary Medical Center Torrance
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06520
      • Yale New Haven Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Hospital
    • Gainesville, Florida, United States, 32608
      • UF Health Shands Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center Jacksonville
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital
    • Port Saint Lucie, Florida, United States, 34987
      • Cleveland Clinic Tradition Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Atlanta, Georgia, United States, 30303
      • Emory University Hospital
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Illinois
    • Carbondale, Illinois, United States, 62901
      • Memorial Hospital of Carbondale
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital
    • Evanston, Illinois, United States, 60201
      • Evanston Hospital
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
    • Rockford, Illinois, United States, 61114
      • Javon Bea Hospital - Riverside
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center - Main Campus
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Flint, Michigan, United States, 48532
      • McLaren Flint
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Macomb
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Edina, Minnesota, United States, 55414
      • M Health Fairview Southdale Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • M Health Fairview University of Minnesota Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care
    • St Louis, Missouri, United States, 62269
      • Barnes Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore University Medical Center
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital Center
    • Brooklyn, New York, United States, 11220
      • NYU Langone Hospital - Brooklyn
    • Buffalo, New York, United States, 14202
      • Buffalo General Medical Center
    • Lake Success, New York, United States, 11042
      • North Shore University Hospital
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
    • New York, New York, United States, 10021
      • NYP Weill Cornell Medical Center
    • New York, New York, United States, 10032
      • NYP Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • Strong Memorial Hospital
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
    • Greensboro, North Carolina, United States, 27405
      • Moses H. Cone Memorial Hospital
    • Greenville, North Carolina, United States, 27834
      • ECU Health Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • OSU Wexner Medical Center
    • Toledo, Ohio, United States, 43608
      • Mercy St. Vincent Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University Hospital
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Altoona, Pennsylvania, United States, 16601
      • UPMC Altoona
    • Erie, Pennsylvania, United States, 16550
      • UPMC Hamot
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital, Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina University Hospital
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist University Hospital
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Memorial Hermann Texas Medical Center
    • Lubbock, Texas, United States, 79410
      • Covenant Medical Center
    • Plano, Texas, United States, 75075
      • Medical City Plano
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center San Antonio
    • Tyler, Texas, United States, 75708
      • UT Health Tyler
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • UVA Medical Center
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Roanoke, Virginia, United States, 24011
      • Carilion Roanoke Memorial Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center - Cherry Hill Campus
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute focal symptoms or signs of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal to 24 hours that occurred within 30 days prior to randomization
• Index stroke is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, middle cerebral artery (M1 or M2), vertebral artery (V4), basilar artery, posterior cerebral artery (P1), or anterior cerebral artery (A1)) documented by CTA, MRA, or catheter angiography
• Modified Rankin Scale score of ≤ 4, at time of consent
• Ability to swallow pills
• At least 30 years of age, inclusive, at time of consent

• Subjects 30-49 years of age are required to meet at least ONE of the following additional criteria below to qualify for the study:

  1. diabetes treated with insulin for at least 15 years
  2. at least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL < 40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; any of the following vascular events occurring in a parent or sibling who was < 55 years of age for men or < 65 years of age for women at the time of the event: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery for atherosclerotic disease
  3. personal history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease
  4. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic
  5. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography
  6. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic
• Negative pregnancy test in a female who has had any menses in the last 18 months and has not had surgery that would make her unable to become pregnant
• Subject is willing and able to return for all follow-up evaluations required by the protocol
• Subject is available by phone
• Subject understands the purpose and requirements of the study and can make him/herself understood
• Subject has provided informed consent (use of a LAR is not permitted)

Exclusion Criteria:

• Previous treatment of qualifying intracranial artery with a stent, angioplasty, or other mechanical device, including mechanical thrombectomy for the qualifying stroke, or plan to perform one of these procedures
• Plan to perform concomitant endarterectomy, angioplasty or stenting of an extracranial vessel tandem to the symptomatic intracranial stenosis
• Intracranial tumor (except meningioma) or any intracranial vascular malformation
• Thrombolytic therapy within 24 hours prior to randomization
• Progressive neurological signs within 24 hours prior to randomization
• History of spontaneous non-traumatic intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
• Intracranial arterial stenosis due to: arterial dissection; MoyaMoya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process; reversible cerebral vasoconstriction syndrome (RCVS); suspected recanalized embolus
• Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, left atrial spontaneous echo contrast
• Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel, or ticagrelor
• Uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), active peptic ulcer disease, major systemic hemorrhage within 30 days prior to randomization, active bleed or bleeding diathesis, platelets < 100,000, hematocrit < 30, INR > 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, severe liver impairment (AST or ALT > 3 x normal, cirrhosis), or CrCl < 15 mL/min or on dialysis
• Major surgery (including stenting of any vessel; open femoral, aortic, or carotid surgery; or cardiac surgery) within previous 30 days prior to randomization or planned in the next 90 days after randomization
• Any condition other than intracranial arterial stenosis that requires the subject to take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for subcutaneous heparin or enoxaparin for deep vein thrombosis (DVT) prophylaxis)
• Dementia or psychiatric problem that prevents the subject from following an outpatient program reliably
• Co-morbid conditions that may limit survival to less than 12 months
• Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study, or currently breastfeeding
• Current or anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or CYP3A4 substrates that cannot be stopped for the course of this study
• Enrollment in another study that would conflict with the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm: Ticagrelor and Aspirin; Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily)	Drug: Ticagrelor + Aspirin; ticagrelor (180 mg loading dose, then 90mg twice daily) and aspirin (81mg daily); Other Names: Brilinta; Other: Risk Factor Management; Risk factors for stroke (LDL, blood pressure, non-HDL cholesterol, diabetes, smoking, weight, and physical activity) will be monitored and managed.
Active Comparator: Standard of Care Arm: Clopidogrel and Aspirin; Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily)	Other: Risk Factor Management; Risk factors for stroke (LDL, blood pressure, non-HDL cholesterol, diabetes, smoking, weight, and physical activity) will be monitored and managed.; Drug: Clopidogrel + Aspirin; clopidogrel (600mg loading dose, then 75mg daily) and aspirin (81mg daily); Other Names: Plavix
Experimental: Experimental Arm: Rivaroxaban and Aspirin; Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)	Other: Risk Factor Management; Risk factors for stroke (LDL, blood pressure, non-HDL cholesterol, diabetes, smoking, weight, and physical activity) will be monitored and managed.; Drug: Rivaroxaban + Aspirin; low dose rivaroxaban (2.5mg twice daily) and aspirin (81mg daily); Other Names: Xarelto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with parenchymal ICH or non-ICH major hemorrhage	Non-ICH major hemorrhage is derived from the International Society on Thrombosis and Haemostasis (ISTH) criteria consisting of any of the following: Fatal bleeding; Symptomatic bleeding in a critical area or organ, such as subarachnoid, intraventricular, subdural, epidural, spinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome; Symptomatic bleeding causing a fall in hemoglobin level of 1.24 mmol/L (20g/L or greater) or more, or leading to transfusion of two units or more of whole blood or red cells	Up to 12 months
Number of participants with ischemic stroke, intracerebral hemorrhage or vascular death	The definition of ischemic stroke is the American Heart Association definition that includes acute focal signs or symptoms of cerebral, spinal cord, or retinal involvement of any duration associated with imaging, pathological, or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord, or retinal focal arterial ischemic injury based on symptoms persisting greater than or equal to 24 hours.	Up to 12 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Medical University of South Carolina; National Institute of Neurological Disorders and Stroke (NINDS); AstraZeneca; Janssen Scientific Affairs, LLC; University of Cincinnati
• Investigators: Principal Investigator: Brian L. Hoh, MD, MBA, University of Florida; Principal Investigator: Marc I. Chimowitz, MBChB, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intracranial Arterial Diseases; Stroke; Intracranial Arteriosclerosis; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Purines; Phenols; Benzene Derivatives; Nucleosides; Ribonucleosides; Morpholines; Oxazines; Thiophenes; Salicylates; Hydroxybenzoates; Adenosine; Purine Nucleosides; Ticlopidine; Thienopyridines; Ticagrelor; Clopidogrel; Rivaroxaban; Aspirin
• Other Study ID Numbers: CED000000522; AWD10099 (Other Identifier: UFIRST); U01NS117450 (U.S. NIH Grant/Contract)

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