Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis
- Conditions
- StrokeIntracranial Arteriosclerosis
- Interventions
- Other: Risk Factor Management
- Registration Number
- NCT05047172
- Lead Sponsor
- University of Florida
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1683
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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
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Subject is willing and able to return for all follow-up evaluations required by the protocol
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Subject is available by phone
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Subject understands the purpose and requirements of the study and can make him/herself understood
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Subject has provided informed consent (use of a LAR is not permitted)
- Previous treatment of target lesion 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 any 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 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of Care Arm: Clopidogrel and Aspirin Clopidogrel + Aspirin Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily) Experimental Arm: Rivaroxaban and Aspirin Rivaroxaban + Aspirin Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily) Experimental Arm: Ticagrelor and Aspirin Ticagrelor + Aspirin Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily) Experimental Arm: Ticagrelor and Aspirin Risk Factor Management Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily) Standard of Care Arm: Clopidogrel and Aspirin Risk Factor Management Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily) Experimental Arm: Rivaroxaban and Aspirin Risk Factor Management Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)
- Primary Outcome Measures
Name Time Method Number of participants with parenchymal ICH or non-ICH major hemorrhage Up to 12 months 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 cellsNumber of participants with ischemic stroke, intracerebral hemorrhage or vascular death Up to 12 months 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (125)
University of Alabama Hospital
🇺🇸Birmingham, Alabama, United States
University of South Alabama University Hospital
🇺🇸Mobile, Alabama, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
HonorHealth Scottsdale Osborn Medical Center
🇺🇸Scottsdale, Arizona, United States
Banner University Medical Center - Tucson Campus
🇺🇸Tucson, Arizona, United States
Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
The Neuron Clinic - Chula Vista
🇺🇸Chula Vista, California, United States
Kaiser Permanente Fontana Medical Center
🇺🇸Fontana, California, United States
UCSD Health La Jolla
🇺🇸La Jolla, California, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Los Alamitos Medical Center
🇺🇸Los Alamitos, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center, Los Angeles, CA
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Salinas Valley Memorial Hospital
🇺🇸Salinas, California, United States
UCSD Medical Center - Hillcrest Hospital
🇺🇸San Diego, California, United States
Providence Little Company of Mary Medical Center Torrance
🇺🇸Torrance, California, United States
PIH Health Hospital
🇺🇸Whittier, California, United States
St. Mary's Medical Center
🇺🇸Grand Junction, Colorado, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Morton Plant Hospital
🇺🇸Clearwater, Florida, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Baptist Medical Center Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
Jackson Memorial Hospital
🇺🇸Miami, Florida, United States
Cleveland Clinic Tradition Hospital
🇺🇸Port Saint Lucie, Florida, United States
Intercoastal Medical Group - Clinical Research
🇺🇸Sarasota, Florida, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
NCH Hospital
🇺🇸Arlington Heights, Illinois, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Illinois Hospital
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Javon Bea Hospital - Riverside
🇺🇸Rockford, Illinois, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
Ochsner Medical Center - Main Campus
🇺🇸New Orleans, Louisiana, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
McLaren Flint
🇺🇸Flint, Michigan, United States
McLaren Macomb
🇺🇸Mount Clemens, Michigan, United States
Metro Health Hospital
🇺🇸Wyoming, Michigan, United States
M Health Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Abbott Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
M Health Fairview University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Missouri Health Care
🇺🇸Columbia, Missouri, United States
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
Valley Hospital
🇺🇸Ridgewood, New Jersey, United States
University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Kings County Hospital Center
🇺🇸Brooklyn, New York, United States
SUNY Downstate Medical Center
🇺🇸Brooklyn, New York, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
NYU Langone Hospital - Brooklyn
🇺🇸Brooklyn, New York, United States
Buffalo General Medical Center
🇺🇸Buffalo, New York, United States
North Shore University Hospital
🇺🇸Lake Success, New York, United States
NYU Langone Medical Center - Tisch Hospital
🇺🇸New York, New York, United States
NYP Weill Cornell Medical Center
🇺🇸New York, New York, United States
The Mount Sinai Hospital
🇺🇸New York, New York, United States
NYP Columbia University Medical Center
🇺🇸New York, New York, United States
Strong Memorial Hospital
🇺🇸Rochester, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Moses H. Cone Memorial Hospital
🇺🇸Greensboro, North Carolina, United States
ECU Health Medical Center
🇺🇸Greenville, North Carolina, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic Akron General
🇺🇸Akron, Ohio, United States
Good Samaritan Hospital
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
UH Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
Mercy St. Vincent Medical Center
🇺🇸Toledo, Ohio, United States
OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health & Science University Hospital
🇺🇸Portland, Oregon, United States
Jefferson Abington Hospital
🇺🇸Abington, Pennsylvania, United States
UPMC Altoona
🇺🇸Altoona, Pennsylvania, United States
UPMC Hamot
🇺🇸Erie, Pennsylvania, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital, Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Medical University of South Carolina University Hospital
🇺🇸Charleston, South Carolina, United States
Prisma Health Richland Hospital
🇺🇸Columbia, South Carolina, United States
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
Methodist University Hospital
🇺🇸Memphis, Tennessee, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
Covenant Medical Center
🇺🇸Lubbock, Texas, United States
Medical City Plano
🇺🇸Plano, Texas, United States
University of Texas Health Science Center San Antonio
🇺🇸San Antonio, Texas, United States
UT Health Tyler
🇺🇸Tyler, Texas, United States
University of Utah Healthcare
🇺🇸Salt Lake City, Utah, United States
The University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
UVA Medical Center
🇺🇸Charlottesville, Virginia, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Carilion Roanoke Memorial Hospital
🇺🇸Roanoke, Virginia, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Swedish Medical Center - Cherry Hill Campus
🇺🇸Seattle, Washington, United States
WVU Healthcare Ruby Memorial Hospital
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin University Hospital
🇺🇸Madison, Wisconsin, United States
Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada