Clinical trial NCT05047172: Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis
Official title: Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Intracranial Arteriosclerosis
Stroke
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Cincinnati
name: Medical University of South Carolina
name: Janssen Scientific Affairs, LLC
name: AstraZeneca
First posted: 2021-09-17
Enrollment: 1683
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with parenchymal ICH or non-ICH major hemorrhage
timeFrame: Up to 12 months
measure: Number of participants with ischemic stroke, intracerebral hemorrhage or vascular death
timeFrame: Up to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama University Hospital
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Osborn Medical Center
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson Campus
state: Arizona
city: Carmichael
country: United States
facility: Mercy San Juan Medical Center
state: California
city: Chula Vista
country: United States
facility: The Neuron Clinic - Chula Vista
state: California
city: Fontana
country: United States
facility: Kaiser Permanente Fontana Medical Center
state: California
city: La Jolla
country: United States
facility: UCSD Health La Jolla
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Alamitos
country: United States
facility: Los Alamitos Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Los Angeles, CA
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Salinas
country: United States
facility: Salinas Valley Memorial Hospital
state: California
city: San Diego
country: United States
facility: UCSD Medical Center - Hillcrest Hospital
state: California
city: Torrance
country: United States
facility: Providence Little Company of Mary Medical Center Torrance
state: California
city: Whittier
country: United States
facility: PIH Health Hospital
state: California
city: Grand Junction
country: United States
facility: St. Mary's Medical Center
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Port Saint Lucie
country: United States
facility: Cleveland Clinic Tradition Hospital
state: Florida
city: Sarasota
country: United States
facility: Intercoastal Medical Group - Clinical Research
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Arlington Heights
country: United States
facility: NCH Hospital
state: Illinois
city: Carbondale
country: United States
facility: Memorial Hospital of Carbondale
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Rockford
country: United States
facility: Javon Bea Hospital - Riverside
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center - Main Campus
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: McLaren Flint
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Macomb
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Edina
country: United States
facility: M Health Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: Kings County Hospital Center
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Brooklyn
country: United States
facility: NYU Langone Hospital - Brooklyn
state: New York
city: Buffalo
country: United States
facility: Buffalo General Medical Center
state: New York
city: Lake Success
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center - Tisch Hospital
state: New York
city: New York
country: United States
facility: NYP Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: NYP Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Greensboro
country: United States
facility: Moses H. Cone Memorial Hospital
state: North Carolina
city: Greenville
country: United States
facility: ECU Health Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Cleveland Clinic Akron General
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: UH Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: Mercy St. Vincent Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: OU Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Abington
country: United States
facility: Jefferson Abington Hospital
state: Pennsylvania
city: Altoona
country: United States
facility: UPMC Altoona
state: Pennsylvania
city: Erie
country: United States
facility: UPMC Hamot
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital, Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina University Hospital
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Greenville Memorial Hospital
state: South Carolina
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
city: Lubbock
country: United States
facility: Covenant Medical Center
state: Texas
city: Plano
country: United States
facility: Medical City Plano
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
city: Tyler
country: United States
facility: UT Health Tyler
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Healthcare
state: Utah
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: UVA Medical Center
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center - Cherry Hill Campus
state: Washington
city: Morgantown
country: United States
facility: WVU Healthcare Ruby Memorial Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin University Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
affiliation: University of Florida
name: Brian L. Hoh, MD, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Marc I. Chimowitz, MBChB
role: PRINCIPAL_INVESTIGATOR
References: