Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis
Purpose
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.
Conditions
- Intracranial Arteriosclerosis
- Stroke
Eligibility
- Eligible Ages
- Over 30 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- 1:1:1 treatment allocation
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Experimental Arm: Ticagrelor and Aspirin |
Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily) |
|
|
Active Comparator Standard of Care Arm: Clopidogrel and Aspirin |
Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily) |
|
|
Experimental Experimental Arm: Rivaroxaban and Aspirin |
Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily) |
|
Recruiting Locations
University of South Alabama University Hospital
Mobile, Alabama 36604
Mobile, Alabama 36604
St. Joseph's Hospital and Medical Center
Phoenix, Arizona 85013
Phoenix, Arizona 85013
Mercy San Juan Medical Center
Carmichael, California 95608
Carmichael, California 95608
The Neuron Clinic - Chula Vista
Chula Vista, California 91910
Chula Vista, California 91910
Kaiser Permanente Fontana Medical Center
Fontana, California 92335
Fontana, California 92335
Long Beach Memorial Medical Center
Long Beach, California 90806
Long Beach, California 90806
Los Alamitos Medical Center
Los Alamitos, California 90720
Los Alamitos, California 90720
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California 90027
Los Angeles, California 90027
UC Davis Medical Center
Sacramento, California 95817
Sacramento, California 95817
Providence Little Company of Mary Medical Center Torrance
Torrance, California 90503
Torrance, California 90503
St. Mary's Medical Center
Grand Junction, Colorado 81501
Grand Junction, Colorado 81501
MedStar Washington Hospital Center
Washington, District of Columbia 20010
Washington, District of Columbia 20010
Baptist Medical Center Jacksonville
Jacksonville, Florida 32207
Jacksonville, Florida 32207
Cleveland Clinic Tradition Hospital
Port Saint Lucie, Florida 34987
Port Saint Lucie, Florida 34987
Emory University Hospital
Atlanta, Georgia 30303
Atlanta, Georgia 30303
Grady Memorial Hospital
Atlanta, Georgia 30303
Atlanta, Georgia 30303
Memorial Hospital of Carbondale
Carbondale, Illinois 62901
Carbondale, Illinois 62901
University of Chicago Medical Center
Chicago, Illinois 60637
Chicago, Illinois 60637
Advocate Christ Medical Center
Oak Lawn, Illinois 60453
Oak Lawn, Illinois 60453
Javon Bea Hospital - Riverside
Rockford, Illinois 61114
Rockford, Illinois 61114
University of Kansas Hospital
Kansas City, Kansas 66160
Kansas City, Kansas 66160
Ochsner Medical Center - Main Campus
New Orleans, Louisiana 70121
New Orleans, Louisiana 70121
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
Brigham and Women's Hospital
Boston, Massachusetts 02115
Boston, Massachusetts 02115
Boston Medical Center
Boston, Massachusetts 02118
Boston, Massachusetts 02118
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
Boston, Massachusetts 02215
UMass Memorial Medical Center
Worcester, Massachusetts 01655
Worcester, Massachusetts 01655
Metro Health Hospital
Wyoming, Michigan 49519
Wyoming, Michigan 49519
M Health Fairview Southdale Hospital
Edina, Minnesota 55414
Edina, Minnesota 55414
Abbott Northwestern Hospital
Minneapolis, Minnesota 55407
Minneapolis, Minnesota 55407
M Health Fairview University of Minnesota Medical Center
Minneapolis, Minnesota 55415
Minneapolis, Minnesota 55415
University of Mississippi Medical Center
Jackson, Mississippi 39216
Jackson, Mississippi 39216
University of Missouri Health Care
Columbia, Missouri 65212
Columbia, Missouri 65212
Cooper University Hospital
Camden, New Jersey 08103
Camden, New Jersey 08103
Jersey Shore University Medical Center
Neptune, New Jersey 07753
Neptune, New Jersey 07753
University of New Mexico Hospital
Albuquerque, New Mexico 87106
Albuquerque, New Mexico 87106
SUNY Downstate Medical Center
Brooklyn, New York 11203
Brooklyn, New York 11203
NYU Langone Hospital - Brooklyn
Brooklyn, New York 11220
Brooklyn, New York 11220
North Shore University Hospital
Lake Success, New York 11042
Lake Success, New York 11042
NYP Weill Cornell Medical Center
New York, New York 10021
New York, New York 10021
NYP Columbia University Medical Center
New York, New York 10032
New York, New York 10032
Carolinas Medical Center
Charlotte, North Carolina 28207
Charlotte, North Carolina 28207
Duke University Hospital
Durham, North Carolina 27710
Durham, North Carolina 27710
Moses H. Cone Memorial Hospital
Greensboro, North Carolina 27405
Greensboro, North Carolina 27405
ECU Health Medical Center
Greenville, North Carolina 27834
Greenville, North Carolina 27834
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina 27157
Winston-Salem, North Carolina 27157
University of Cincinnati Medical Center
Cincinnati, Ohio 45267
Cincinnati, Ohio 45267
UH Cleveland Medical Center
Cleveland, Ohio 44106
Cleveland, Ohio 44106
Jefferson Abington Hospital
Abington, Pennsylvania 19001
Abington, Pennsylvania 19001
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19107
Temple University Hospital, Philadelphia
Philadelphia, Pennsylvania 19140
Philadelphia, Pennsylvania 19140
UPMC Presbyterian Hospital
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
Medical University of South Carolina University Hospital
Charleston, South Carolina 29425
Charleston, South Carolina 29425
Prisma Health Richland Hospital
Columbia, South Carolina 29203
Columbia, South Carolina 29203
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina 29605
Greenville, South Carolina 29605
University of Texas Medical Branch
Galveston, Texas 77555
Galveston, Texas 77555
Memorial Hermann Texas Medical Center
Houston, Texas 77030
Houston, Texas 77030
University of Texas Health Science Center San Antonio
San Antonio, Texas 78229
San Antonio, Texas 78229
Carilion Roanoke Memorial Hospital
Roanoke, Virginia 24011
Roanoke, Virginia 24011
Swedish Medical Center - Cherry Hill Campus
Seattle, Washington 98122
Seattle, Washington 98122
More Details
- NCT ID
- NCT05047172
- Status
- Recruiting
- Sponsor
- University of Florida
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.