NCT05047172

Brief Summary

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,683

participants targeted

Target at P75+ for phase_3

Timeline
9mo left

Started Aug 2022

Typical duration for phase_3

Geographic Reach
1 country

117 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Aug 2022Jan 2027

First Submitted

Initial submission to the registry

September 7, 2021

Completed
10 days until next milestone

First Posted

Study publicly available on registry

September 17, 2021

Completed
11 months until next milestone

Study Start

First participant enrolled

August 2, 2022

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Last Updated

April 15, 2026

Status Verified

April 1, 2026

Enrollment Period

4.4 years

First QC Date

September 7, 2021

Last Update Submit

April 13, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • 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

Study Arms (3)

Experimental Arm: Ticagrelor and Aspirin

EXPERIMENTAL

Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily)

Drug: Ticagrelor + AspirinOther: Risk Factor Management

Standard of Care Arm: Clopidogrel and Aspirin

ACTIVE COMPARATOR

Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily)

Drug: Clopidogrel + AspirinOther: Risk Factor Management

Experimental Arm: Rivaroxaban and Aspirin

EXPERIMENTAL

Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)

Drug: Rivaroxaban + AspirinOther: Risk Factor Management

Interventions

ticagrelor (180 mg loading dose, then 90mg twice daily) and aspirin (81mg daily)

Also known as: Brilinta
Experimental Arm: Ticagrelor and Aspirin

low dose rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)

Also known as: Xarelto
Experimental Arm: Rivaroxaban and Aspirin

clopidogrel (600mg loading dose, then 75mg daily) and aspirin (81mg daily)

Also known as: Plavix
Standard of Care Arm: Clopidogrel and Aspirin

Risk factors for stroke (LDL, blood pressure, non-HDL cholesterol, diabetes, smoking, weight, and physical activity) will be monitored and managed.

Experimental Arm: Rivaroxaban and AspirinExperimental Arm: Ticagrelor and AspirinStandard of Care Arm: Clopidogrel and Aspirin

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • diabetes treated with insulin for at least 15 years
  • 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
  • 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
  • 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
  • aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography
  • 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
  • +2 more criteria

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (117)

University of Alabama Hospital

Birmingham, Alabama, 35233, United States

Location

University of South Alabama University Hospital

Mobile, Alabama, 36604, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mercy San Juan Medical Center

Carmichael, California, 95608, United States

Location

The Neuron Clinic - Chula Vista

Chula Vista, California, 91910, United States

Location

Kaiser Permanente Fontana Medical Center

Fontana, California, 92335, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Los Alamitos Medical Center

Los Alamitos, California, 90720, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Ronald Reagan UCLA Medical Center, Los Angeles, CA

Los Angeles, California, 90095, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Salinas Valley Memorial Hospital

Salinas, California, 93901, United States

Location

UCSD Medical Center - Hillcrest Hospital

San Diego, California, 92103, United States

Location

Providence Little Company of Mary Medical Center Torrance

Torrance, California, 90503, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

St. Mary's Medical Center

Grand Junction, Colorado, 81501, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

Broward Health Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32608, United States

Location

Baptist Medical Center Jacksonville

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Cleveland Clinic Tradition Hospital

Port Saint Lucie, Florida, 34987, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Emory University Hospital

Atlanta, Georgia, 30303, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Memorial Hospital of Carbondale

Carbondale, Illinois, 62901, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois Hospital

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Endeavor Health Edward Hospital

Naperville, Illinois, 60540, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Javon Bea Hospital - Riverside

Rockford, Illinois, 61114, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

University of Kentucky Hospital

Lexington, Kentucky, 40536, United States

Location

Ochsner Medical Center - Main Campus

New Orleans, Louisiana, 70121, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

McLaren Flint

Flint, Michigan, 48532, United States

Location

McLaren Macomb

Mount Clemens, Michigan, 48043, United States

Location

Metro Health Hospital

Wyoming, Michigan, 49519, United States

Location

M Health Fairview Southdale Hospital

Edina, Minnesota, 55414, United States

Location

Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55415, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65212, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 62269, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

Location

Kings County Hospital Center

Brooklyn, New York, 11203, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

NYU Langone Hospital - Brooklyn

Brooklyn, New York, 11220, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14202, United States

Location

North Shore University Hospital

Lake Success, New York, 11042, United States

Location

NYP Weill Cornell Medical Center

New York, New York, 10021, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

NYP Columbia University Medical Center

New York, New York, 10032, United States

Location

Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Moses H. Cone Memorial Hospital

Greensboro, North Carolina, 27405, United States

Location

ECU Health Medical Center

Greenville, North Carolina, 27834, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Akron General

Akron, Ohio, 44307, United States

Location

Good Samaritan Hospital

Cincinnati, Ohio, 45220, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

UH Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Toledo Hospital

Toledo, Ohio, 43606, United States

Location

Mercy St. Vincent Medical Center

Toledo, Ohio, 43608, United States

Location

OU Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Oregon Health & Science University Hospital

Portland, Oregon, 97239, United States

Location

Jefferson Abington Hospital

Abington, Pennsylvania, 19001, United States

Location

UPMC Altoona

Altoona, Pennsylvania, 16601, United States

Location

UPMC Hamot

Erie, Pennsylvania, 16550, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital, Philadelphia

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina University Hospital

Charleston, South Carolina, 29425, United States

Location

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

Location

Prisma Health Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38104, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States

Location

Covenant Medical Center

Lubbock, Texas, 79410, United States

Location

Medical City Plano

Plano, Texas, 75075, United States

Location

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

UT Health Tyler

Tyler, Texas, 75708, United States

Location

The University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

UVA Medical Center

Charlottesville, Virginia, 22903, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, 24011, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Swedish Medical Center - Cherry Hill Campus

Seattle, Washington, 98122, United States

Location

University of Wisconsin University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Intracranial ArteriosclerosisStroke

Interventions

TicagrelorAspirinRivaroxabanClopidogrel

Condition Hierarchy (Ancestors)

Intracranial Arterial DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

AdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesSalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsThiophenesSulfur CompoundsMorpholinesOxazinesHeterocyclic Compounds, 1-RingTiclopidineThienopyridinesPyridines

Study Officials

  • Brian L. Hoh, MD, MBA

    University of Florida

    PRINCIPAL INVESTIGATOR
  • Marc I. Chimowitz, MBChB

    Medical University of South Carolina

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
1:1:1 treatment allocation
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 7, 2021

First Posted

September 17, 2021

Study Start

August 2, 2022

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Last Updated

April 15, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations