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 Alabama Hospital
Birmingham 4049979, Alabama 4829764 35233
Birmingham 4049979, Alabama 4829764 35233
University of South Alabama University Hospital
Mobile 4076598, Alabama 4829764 36604
Mobile 4076598, Alabama 4829764 36604
St. Joseph's Hospital and Medical Center
Phoenix 5308655, Arizona 5551752 85013
Phoenix 5308655, Arizona 5551752 85013
Mercy San Juan Medical Center
Carmichael 5334336, California 5332921 95608
Carmichael 5334336, California 5332921 95608
The Neuron Clinic - Chula Vista
Chula Vista 5336899, California 5332921 91910
Chula Vista 5336899, California 5332921 91910
Kaiser Permanente Fontana Medical Center
Fontana 5349755, California 5332921 92335
Fontana 5349755, California 5332921 92335
Long Beach Memorial Medical Center
Long Beach 5367929, California 5332921 90806
Long Beach 5367929, California 5332921 90806
Los Alamitos Medical Center
Los Alamitos 5368304, California 5332921 90720
Los Alamitos 5368304, California 5332921 90720
Kaiser Permanente Los Angeles Medical Center
Los Angeles 5368361, California 5332921 90027
Los Angeles 5368361, California 5332921 90027
UC Davis Medical Center
Sacramento 5389489, California 5332921 95817
Sacramento 5389489, California 5332921 95817
Providence Little Company of Mary Medical Center Torrance
Torrance 5403022, California 5332921 90503
Torrance 5403022, California 5332921 90503
University of Colorado Hospital
Aurora 5412347, Colorado 5417618 80045
Aurora 5412347, Colorado 5417618 80045
St. Mary's Medical Center
Grand Junction 5423573, Colorado 5417618 81501
Grand Junction 5423573, Colorado 5417618 81501
Hartford Hospital
Hartford 4835797, Connecticut 4831725 06102
Hartford 4835797, Connecticut 4831725 06102
Yale New Haven Hospital
New Haven 4839366, Connecticut 4831725 06520
New Haven 4839366, Connecticut 4831725 06520
MedStar Washington Hospital Center
Washington D.C. 4140963, District of Columbia 4138106 20010
Washington D.C. 4140963, District of Columbia 4138106 20010
Morton Plant Hospital
Clearwater 4151316, Florida 4155751 33756
Clearwater 4151316, Florida 4155751 33756
Broward Health Medical Center
Fort Lauderdale 4155966, Florida 4155751 33316
Fort Lauderdale 4155966, Florida 4155751 33316
UF Health Shands Hospital
Gainesville 4156404, Florida 4155751 32608
Gainesville 4156404, Florida 4155751 32608
Baptist Medical Center Jacksonville
Jacksonville 4160021, Florida 4155751 32207
Jacksonville 4160021, Florida 4155751 32207
Jackson Memorial Hospital
Miami 4164138, Florida 4155751 33136
Miami 4164138, Florida 4155751 33136
Cleveland Clinic Tradition Hospital
Port Saint Lucie 4169171, Florida 4155751 34987
Port Saint Lucie 4169171, Florida 4155751 34987
Emory University Hospital
Atlanta 4180439, Georgia 4197000 30303
Atlanta 4180439, Georgia 4197000 30303
Grady Memorial Hospital
Atlanta 4180439, Georgia 4197000 30303
Atlanta 4180439, Georgia 4197000 30303
Memorial Hospital of Carbondale
Carbondale 4235193, Illinois 4896861 62901
Carbondale 4235193, Illinois 4896861 62901
Rush University Medical Center
Chicago 4887398, Illinois 4896861 60612
Chicago 4887398, Illinois 4896861 60612
University of Illinois Hospital
Chicago 4887398, Illinois 4896861 60612
Chicago 4887398, Illinois 4896861 60612
University of Chicago Medical Center
Chicago 4887398, Illinois 4896861 60637
Chicago 4887398, Illinois 4896861 60637
Evanston Hospital
Evanston 4891382, Illinois 4896861 60201
Evanston 4891382, Illinois 4896861 60201
Javon Bea Hospital - Riverside
Rockford 4907959, Illinois 4896861 61114
Rockford 4907959, Illinois 4896861 61114
University of Kansas Hospital
Kansas City 4273837, Kansas 4273857 66160
Kansas City 4273837, Kansas 4273857 66160
Baptist Health Lexington
Lexington 4297983, Kentucky 6254925 40503
Lexington 4297983, Kentucky 6254925 40503
Ochsner Medical Center - Main Campus
New Orleans 4335045, Louisiana 4331987 70121
New Orleans 4335045, Louisiana 4331987 70121
Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Boston 4930956, Massachusetts 6254926 02114
Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926 02115
Boston 4930956, Massachusetts 6254926 02115
Boston Medical Center
Boston 4930956, Massachusetts 6254926 02118
Boston 4930956, Massachusetts 6254926 02118
Beth Israel Deaconess Medical Center
Boston 4930956, Massachusetts 6254926 02215
Boston 4930956, Massachusetts 6254926 02215
McLaren Flint
Flint 4992982, Michigan 5001836 48532
Flint 4992982, Michigan 5001836 48532
McLaren Macomb
Mount Clemens 5002656, Michigan 5001836 48043
Mount Clemens 5002656, Michigan 5001836 48043
Metro Health Hospital
Wyoming 5015618, Michigan 5001836 49519
Wyoming 5015618, Michigan 5001836 49519
M Health Fairview Southdale Hospital
Edina 5025264, Minnesota 5037779 55414
Edina 5025264, Minnesota 5037779 55414
Abbott Northwestern Hospital
Minneapolis 5037649, Minnesota 5037779 55407
Minneapolis 5037649, Minnesota 5037779 55407
M Health Fairview University of Minnesota Medical Center
Minneapolis 5037649, Minnesota 5037779 55415
Minneapolis 5037649, Minnesota 5037779 55415
University of Mississippi Medical Center
Jackson 4431410, Mississippi 4436296 39216
Jackson 4431410, Mississippi 4436296 39216
University of Missouri Health Care
Columbia 4381982, Missouri 4398678 65212
Columbia 4381982, Missouri 4398678 65212
Barnes Jewish Hospital
St Louis 4407066, Missouri 4398678 62269
St Louis 4407066, Missouri 4398678 62269
University of Nebraska Medical Center
Omaha 5074472, Nebraska 5073708 68198
Omaha 5074472, Nebraska 5073708 68198
Cooper University Hospital
Camden 4501018, New Jersey 5101760 08103
Camden 4501018, New Jersey 5101760 08103
Jersey Shore University Medical Center
Neptune City 5101687, New Jersey 5101760 07753
Neptune City 5101687, New Jersey 5101760 07753
University of New Mexico Hospital
Albuquerque 5454711, New Mexico 5481136 87106
Albuquerque 5454711, New Mexico 5481136 87106
Kings County Hospital Center
Brooklyn 5110302, New York 5128638 11203
Brooklyn 5110302, New York 5128638 11203
SUNY Downstate Medical Center
Brooklyn 5110302, New York 5128638 11203
Brooklyn 5110302, New York 5128638 11203
NYU Langone Hospital - Brooklyn
Brooklyn 5110302, New York 5128638 11220
Brooklyn 5110302, New York 5128638 11220
Buffalo General Medical Center
Buffalo 5110629, New York 5128638 14202
Buffalo 5110629, New York 5128638 14202
North Shore University Hospital
Lake Success 5123853, New York 5128638 11042
Lake Success 5123853, New York 5128638 11042
NYP Weill Cornell Medical Center
New York 5128581, New York 5128638 10021
New York 5128581, New York 5128638 10021
The Mount Sinai Hospital
New York 5128581, New York 5128638 10029
New York 5128581, New York 5128638 10029
NYP Columbia University Medical Center
New York 5128581, New York 5128638 10032
New York 5128581, New York 5128638 10032
Carolinas Medical Center
Charlotte 4460243, North Carolina 4482348 28207
Charlotte 4460243, North Carolina 4482348 28207
Duke University Hospital
Durham 4464368, North Carolina 4482348 27710
Durham 4464368, North Carolina 4482348 27710
Moses H. Cone Memorial Hospital
Greensboro 4469146, North Carolina 4482348 27405
Greensboro 4469146, North Carolina 4482348 27405
ECU Health Medical Center
Greenville 4469160, North Carolina 4482348 27834
Greenville 4469160, North Carolina 4482348 27834
Wake Forest Baptist Medical Center
Winston-Salem 4499612, North Carolina 4482348 27157
Winston-Salem 4499612, North Carolina 4482348 27157
Cleveland Clinic Akron General
Akron 5145476, Ohio 5165418 44307
Akron 5145476, Ohio 5165418 44307
Good Samaritan Hospital
Cincinnati 4508722, Ohio 5165418 45220
Cincinnati 4508722, Ohio 5165418 45220
University of Cincinnati Medical Center
Cincinnati 4508722, Ohio 5165418 45267
Cincinnati 4508722, Ohio 5165418 45267
UH Cleveland Medical Center
Cleveland 5150529, Ohio 5165418 44106
Cleveland 5150529, Ohio 5165418 44106
OSU Wexner Medical Center
Columbus 4509177, Ohio 5165418 43210
Columbus 4509177, Ohio 5165418 43210
Toledo Hospital
Toledo 5174035, Ohio 5165418 43606
Toledo 5174035, Ohio 5165418 43606
Mercy St. Vincent Medical Center
Toledo 5174035, Ohio 5165418 43608
Toledo 5174035, Ohio 5165418 43608
OU Medical Center
Oklahoma City 4544349, Oklahoma 4544379 73104
Oklahoma City 4544349, Oklahoma 4544379 73104
Jefferson Abington Hospital
Abington 5177773, Pennsylvania 6254927 19001
Abington 5177773, Pennsylvania 6254927 19001
Hospital of the University of Pennsylvania
Philadelphia 4560349, Pennsylvania 6254927 19104
Philadelphia 4560349, Pennsylvania 6254927 19104
Thomas Jefferson University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19107
Philadelphia 4560349, Pennsylvania 6254927 19107
Temple University Hospital, Philadelphia
Philadelphia 4560349, Pennsylvania 6254927 19140
Philadelphia 4560349, Pennsylvania 6254927 19140
UPMC Presbyterian Hospital
Pittsburgh 5206379, Pennsylvania 6254927 15213
Pittsburgh 5206379, Pennsylvania 6254927 15213
Rhode Island Hospital
Providence 5224151, Rhode Island 5224323 02903
Providence 5224151, Rhode Island 5224323 02903
Medical University of South Carolina University Hospital
Charleston 4574324, South Carolina 4597040 29425
Charleston 4574324, South Carolina 4597040 29425
Prisma Health Richland Hospital
Columbia 4575352, South Carolina 4597040 29203
Columbia 4575352, South Carolina 4597040 29203
Prisma Health Greenville Memorial Hospital
Greenville 4580543, South Carolina 4597040 29605
Greenville 4580543, South Carolina 4597040 29605
Methodist University Hospital
Memphis 4641239, Tennessee 4662168 38104
Memphis 4641239, Tennessee 4662168 38104
University of Texas Medical Branch
Galveston 4692883, Texas 4736286 77555
Galveston 4692883, Texas 4736286 77555
Houston Methodist Hospital
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
Memorial Hermann Texas Medical Center
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
Covenant Medical Center
Lubbock 5525577, Texas 4736286 79410
Lubbock 5525577, Texas 4736286 79410
Medical City Plano
Plano 4719457, Texas 4736286 75075
Plano 4719457, Texas 4736286 75075
University of Texas Health Science Center San Antonio
San Antonio 4726206, Texas 4736286 78229
San Antonio 4726206, Texas 4736286 78229
UVA Medical Center
Charlottesville 4752031, Virginia 6254928 22903
Charlottesville 4752031, Virginia 6254928 22903
Inova Fairfax Hospital
Falls Church 4758390, Virginia 6254928 22042
Falls Church 4758390, Virginia 6254928 22042
Carilion Roanoke Memorial Hospital
Roanoke 4782167, Virginia 6254928 24011
Roanoke 4782167, Virginia 6254928 24011
Swedish Medical Center - Cherry Hill Campus
Seattle 5809844, Washington 5815135 98122
Seattle 5809844, Washington 5815135 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.