Anticoagulation Using Rivaroxaban on Top of Aspirin in Intracranial Atherosclerotic Stenosis

NCT05700266 | Unknown Phase 2 DMC

• 1 other identifier: AA-ICAS
• Study Type: interventional
• Target: 1,180
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary goal of the clinical trial is to test the effect of oral rivaroxaban plus aspirin in patients with recent stroke/ transient ischemic attack (TIA) caused by intracranial artery stenosis. Participants will be divided into 2 groups to receive either oral rivaroxaban plus aspirin or oral clopidogrel plus aspirin. The main question it aims to answer is whether the experimental group (oral rivaroxaban plus aspirin) is superior to the control group ( oral clopidogrel plus aspirin) to lower recurrent stroke/TIA or death in these patients during 1 year of follow-up.

Conditions

Ischemic Stroke; Intracranial Atherosclerosis; Stenosis

Keywords

rivaroxaban, stroke, intracranial atherosclerosis stenosis

Outcome Measures

Primary Outcomes (1)

• any stroke (ischemic or hemorrhagic) or death during 1 year of follow-up

  the primary outcome will be assessed during 1 year of follow-up after recruitments.

Secondary Outcomes (4)

• Changes in the neurological function recovery

  Neurological function will be evaluated at 90 days, 6 months and 1 year after recruitments.

• Major non-intracranial bleeding

  during 1 year of follow-up after recruitments.

• Clinically relevant non-major bleeding

  during 1 year of follow-up after recruitments.

• acute myocardial infarction,acute limb ischemia

  during 1 year of follow-up after recruitments.

Study Arms (2)

Rivaroxaban and Aspirin

EXPERIMENTAL

Rivaroxaban (2.5mg orally twice a day for 90 days) and Aspirin (100mg once a day for 1 year)

Drug: Rivaroxaban; Drug: Aspirin; Other: Risk Factor Management in both arms

Clopidogrel and Aspirin

ACTIVE COMPARATOR

Clopidogrel (300mg loading dose, then 75mg once daily for 90 days) and Aspirin (100mg once a day for 1 year)

Drug: Clopidogrel; Drug: Aspirin; Other: Risk Factor Management in both arms

Interventions

Rivaroxaban DRUG

Rivaroxaban (2.5mg orally twice a day for 90 days)

Rivaroxaban and Aspirin

Clopidogrel DRUG

Clopidogrel (300mg loading dose, then 75mg once daily for 90 days)

Clopidogrel and Aspirin

Aspirin DRUG

Aspirin (100mg once a day for 1 year)

Clopidogrel and Aspirin; Rivaroxaban and Aspirin

Risk Factor Management in both arms OTHER

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

Clopidogrel and Aspirin; Rivaroxaban and Aspirin

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 30 years and ≤ 75 years
• TIA or Acute ischemic stroke that occurred within 30 days prior to randomization.
• Modified Rankin score of ≤ 3
• TIA or Acute ischemic stroke attributed to a 50 to 99% stenosis of a major intracranial artery (internal carotid artery \[ICA\], vertebral artery \[VA\], basilar artery \[BA\] and the M1 segment of middle cerebral artery \[MCA\]). The diagnostic evaluation for ICAS at each site is confirmed by the local investigator, using magnetic resonance angiography (MRA), or computerized tomographic angiography (CTA), high resolution MR, or digital substraction angiography (DSA).
• To increase the likelihood that the symptomatic intracranial stenosis is atherosclerotic, patients aged 30-49 years are required to meet at least one additional criteria (i-vi) below:
• i. insulin dependent diabetes for at least 15 years. ii. at least 2 of the following atherosclerotic risk factors: hypertension (blood pressure ≥ 140/90 or on antihypertensive therapy); dyslipidemia (low density lipoprotein \[LDL\] ≥ 130 mg /dl or high density lipoprotein \[HDL\] \< 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; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was \< 55 years of age for men or \< 65 for women at the time of the event.
• iii. 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.
• iv. 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. v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography.
• vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic.
• Patient agrees with follow-up visits and is available by phone.
• Patient understands the purpose and requirements of the study, can make him/herself understood, and has signed informed consent.

You may not qualify if:

• Previous treatment of target intracranial lesion with a stent, angioplasty, or other mechanical devices (e.g. mechanical thrombectomy, coil embolization)
• Plan to perform angioplasty, stenting, coiling, thrombectomy, endarterectomy or aneurysmal coil embolization for any other cerebral blood vessels (common carotid artery \[CCA\], ICA, VA, MCA, anterior cerebral artery \[ACA\], posterior cerebral artery \[PCA\] et al)
• 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 enrollment
• History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
• Intracranial arterial stenosis due to arterial dissection; MoyaMoya disease; any known vasculitic disease; viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with cerebral spinal fluid 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, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30%
• Known allergy or contraindication to aspirin, clopidogrel or rivaroxaban.
• Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets \< 100,000, hematocrit \< 30, international normalized ration \[INR\] \> 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 (aspartate transaminase \[AST\] or alanine transaminase \[ALT\] \> 3 x normal, cirrhosis), creatinine \> 3.0 (unless on dialysis)
• Major surgery (including open femoral, aortic, cardiac or carotid surgery) within previous 30 days or planned in the next 1 year after enrollment.
• Any condition other than intracranial arterial stenosis that requires the subject to take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for use of subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis while hospitalized)
• Severe neurological deficit that renders the patient incapable of living independently
• Dementia or psychiatric problem that prevents the patient from relevant evaluation or follow-up reliably
• Co-morbid conditions that may limit survival to less than 1 year

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• National Natural Science Foundation of China: collaborator

MeSH Terms

Conditions

Ischemic Stroke; Intracranial Arteriosclerosis; Constriction, Pathologic; Stroke

Interventions

Rivaroxaban; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Arterial Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Kezhong Zhang, Doctor

  The First Affiliated Hospital with Nanjing Medical University

  STUDY CHAIR

Central Study Contacts

Zhaolu Wang, Doctor

CONTACT

+86-18100613663; wangzhaolu123@163.com

Kezhong Zhang, Doctor

CONTACT

+86-13770840575; zhangkezhong8@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Endpoint assessments, including neurological function evaluation, primary and secondary ending points, will be performed blindly by an assessment group who are blind to this study.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This study is an investigator initiated, randomized, blinded endpoint assessment, clinical trial and conducted at 10 sites in the China. Patients meeting the enrollment criteria will be randomly assigned to one of the two treatment groups (1:1) and will be followed up for 1 year.

Study Record Dates

• First Submitted: December 26, 2022
• First Posted: January 26, 2023
• Study Start: December 30, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share