Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis

Stroke Clinical Trial

— CAPTIVA  

Official title:

Comparison of Anti-coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05047172
• Other study ID #: CED000000522
• Secondary ID: AWD10099U01NS117
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2, 2022
• Est. completion date: May 31, 2027

Study information

• Verified date: May 2024
• Source: University of Florida
• Contact: Stephanie McLaren, BSN, RN
• Phone: 888-351-7776
• Email: CAPTIVA-Study[@]ufl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1683
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Arteriosclerosis
• Intracranial Arteriosclerosis
• Stroke

Intervention

Drug:
• Ticagrelor + Aspirin
ticagrelor (180 mg loading dose, then 90mg twice daily) and aspirin (81mg daily)
• Rivaroxaban + Aspirin
low dose rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)
• Clopidogrel + Aspirin
clopidogrel (600mg loading dose, then 75mg daily) and aspirin (81mg daily)

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

Locations

Country	Name	City	State
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	University of New Mexico Hospital	Albuquerque	New Mexico
United States	UPMC Altoona	Altoona	Pennsylvania
United States	NCH Hospital	Arlington Heights	Illinois
United States	Emory University Hospital	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama Hospital	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Kings County Hospital Center	Brooklyn	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	NYU Langone Hospital - Brooklyn	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Buffalo General Medical Center	Buffalo	New York
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Medical University of South Carolina University Hospital	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	UVA Medical Center	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois Hospital	Chicago	Illinois
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	UH Cleveland Medical Center	Cleveland	Ohio
United States	Prisma Health Richland Hospital	Columbia	South Carolina
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	M Health Fairview Southdale Hospital	Edina	Minnesota
United States	UPMC Hamot	Erie	Pennsylvania
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	McLaren Flint	Flint	Michigan
United States	Kaiser Permanente Fontana Medical Center	Fontana	California
United States	UF Health Shands Hospital	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Mary's Medical Center	Grand Junction	Colorado
United States	Moses H. Cone Memorial Hospital	Greensboro	North Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Houston Methodist Hospital	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist Medical Center Jacksonville	Jacksonville	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Hospital	Kansas City	Kansas
United States	UCSD Health La Jolla	La Jolla	California
United States	North Shore University Hospital	Lake Success	New York
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky Hospital	Lexington	Kentucky
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	University of Wisconsin University Hospital	Madison	Wisconsin
United States	Methodist University Hospital	Memphis	Tennessee
United States	Jackson Memorial Hospital	Miami	Florida
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota
United States	University of South Alabama University Hospital	Mobile	Alabama
United States	WVU Healthcare Ruby Memorial Hospital	Morgantown	West Virginia
United States	McLaren Macomb	Mount Clemens	Michigan
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Ochsner Medical Center - Main Campus	New Orleans	Louisiana
United States	NYP Columbia University Medical Center	New York	New York
United States	NYP Weill Cornell Medical Center	New York	New York
United States	NYU Langone Medical Center - Tisch Hospital	New York	New York
United States	The Mount Sinai Hospital	New York	New York
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	OU Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Medical Center	Orange	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University Hospital, Philadelphia	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Medical City Plano	Plano	Texas
United States	Cleveland Clinic Tradition Hospital	Port Saint Lucie	Florida
United States	Oregon Health & Science University Hospital	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Valley Hospital	Ridgewood	New Jersey
United States	Carilion Roanoke Memorial Hospital	Roanoke	Virginia
United States	Strong Memorial Hospital	Rochester	New York
United States	Javon Bea Hospital - Riverside	Rockford	Illinois
United States	UC Davis Medical Center	Sacramento	California
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	Salinas Valley Memorial Hospital	Salinas	California
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	Intercoastal Medical Group - Clinical Research	Sarasota	Florida
United States	HonorHealth Scottsdale Osborn Medical Center	Scottsdale	Arizona
United States	Harborview Medical Center	Seattle	Washington
United States	Tampa General Hospital	Tampa	Florida
United States	Mercy St. Vincent Medical Center	Toledo	Ohio
United States	Banner University Medical Center - Tucson Campus	Tucson	Arizona
United States	UT Health Tyler	Tyler	Texas
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	PIH Health Hospital	Whittier	California
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (6)

Lead Sponsor	Collaborator
University of Florida	AstraZeneca, Janssen Scientific Affairs, LLC, Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS), University of Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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