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

Sponsor

University of Florida (Other)

Overall Status

Recruiting

CT.gov ID

NCT05047172

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH), University of Cincinnati (Other), Medical University of South Carolina (Other), Janssen Scientific Affairs, LLC (Industry), AstraZeneca (Industry)

1,683

Enrollment

Locations

Arms

Anticipated Duration (Months)

60.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intracranial Arteriosclerosis Stroke	Drug: Ticagrelor + Aspirin Drug: Rivaroxaban + Aspirin Drug: Clopidogrel + Aspirin Other: Risk Factor Management	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1683 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

1:1:1 treatment allocation

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 29, 2022

Anticipated Primary Completion Date :

Apr 30, 2027

Anticipated Study Completion Date :

Apr 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm: Ticagrelor and Aspirin Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily)	Drug: Ticagrelor + Aspirin ticagrelor (180 mg loading dose, then 90mg twice daily) and aspirin (81mg daily) Other Names: Brilinta 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.
Active Comparator: Standard of Care Arm: Clopidogrel and Aspirin Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily)	Drug: Clopidogrel + Aspirin clopidogrel (600mg loading dose, then 75mg daily) and aspirin (81mg daily) Other Names: Plavix 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.
Experimental: Experimental Arm: Rivaroxaban and Aspirin Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)	Drug: Rivaroxaban + Aspirin low dose rivaroxaban (2.5mg twice daily) and aspirin (81mg daily) Other Names: Xarelto 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.

Arm

Intervention/Treatment

Experimental: Experimental Arm: Ticagrelor and Aspirin

Ticagrelor (180mg loading dose, then 90mg twice daily) and aspirin (81mg daily)

Drug: Ticagrelor + Aspirin

ticagrelor (180 mg loading dose, then 90mg twice daily) and aspirin (81mg daily)

Other Names:

Brilinta

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.

Active Comparator: Standard of Care Arm: Clopidogrel and Aspirin

Clopidogrel (600mg loading dose, then 75mg once daily) and aspirin (81mg daily)

Drug: Clopidogrel + Aspirin

clopidogrel (600mg loading dose, then 75mg daily) and aspirin (81mg daily)

Other Names:

Plavix

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.

Experimental: Experimental Arm: Rivaroxaban and Aspirin

Rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)

Drug: Rivaroxaban + Aspirin

low dose rivaroxaban (2.5mg twice daily) and aspirin (81mg daily)

Other Names:

Xarelto

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.

Outcome Measures

Primary Outcome Measures

Number of participants with parenchymal brain hemorrhage (ICH) or major non-ICH hemorrhage [Up to 12 months]
Major non-ICH hemorrhage is defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria consisting of: Fatal bleeding, and/or Symptomatic bleeding in a critical area or organ, such as subarachnoid, intraventricular, subdural, epidural, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or 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
Number 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 also includes signs or symptoms lasting < 24 hours associated with an acute infarct on brain imaging.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Symptoms or signs of any duration associated with an infarct on brain imaging that occurred within 30 days prior to randomization
Index infarct is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery) documented by CTA, MRA, or catheter angiography
Modified Rankin score of ≤ 4
Ability to swallow pills
Age 30-80 years, 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
Subject is willing and able to return for all follow-up visits 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 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.
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, uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), severe liver impairment (AST or ALT > 3 x normal, cirrhosis), or CrCl < 15 mL/min or on dialysis
Major surgery (including open femoral, aortic, or carotid surgery, cardiac) 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 while hospitalized)
Severe neurological deficit that renders the subject incapable of living independently
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Fontana Medical Center	Fontana	California	United States	92335
2	UCSD Health La Jolla	La Jolla	California	United States	92093
3	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
4	UCSD Medical Center - Hillcrest Hospital	San Diego	California	United States	92103
5	PIH Health Hospital	Whittier	California	United States	90602
6	Hartford Hospital	Hartford	Connecticut	United States	06102
7	Yale New Haven Hospital	New Haven	Connecticut	United States	06520
8	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
9	UF Health Shands Hospital	Gainesville	Florida	United States	32608
10	University of Illinois Hospital	Chicago	Illinois	United States	60612
11	University of Chicago Medical Center	Chicago	Illinois	United States	60637
12	Ochsner Medical Center - Main Campus	New Orleans	Louisiana	United States	70121
13	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
14	M Health Fairview Southdale Hospital	Edina	Minnesota	United States	55414
15	University of Minnesota Medical Center Hospital	Minneapolis	Minnesota	United States	55415
16	Barnes Jewish Hospital	Saint Louis	Missouri	United States	62269
17	Kings County Hospital Center	Brooklyn	New York	United States	11203
18	Maimonides Medical Center	Brooklyn	New York	United States	11219
19	NYU Langone Hospital - Brooklyn	Brooklyn	New York	United States	11220
20	North Shore University Hospital	Lake Success	New York	United States	11042
21	NYU Langone Medical Center-Tisch Hospital	New York	New York	United States	10016
22	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
23	Good Samaritan Hospital	Cincinnati	Ohio	United States	45220
24	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
25	Medical University of South Carolina University Hospital	Charleston	South Carolina	United States	29425
26	Prisma Health Richland Hospital	Columbia	South Carolina	United States	29203
27	Houston Methodist Hospital	Houston	Texas	United States	77030
28	University of Utah Healthcare	Salt Lake City	Utah	United States	84132

Sponsors and Collaborators

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

Investigators

Principal Investigator: Brian L. Hoh, MD, MBA, University of Florida
Principal Investigator: Marc I. Chimowitz, MBChB, Medical University of South Carolina