Statin and Dual Antiplatelet Therapy to Prevent Early Neurological Deterioration in Branch Atheromatous Disease

NCT04824911 | Completed Phase 2 DMC

• 1 other identifier: 202001386A3
• Study Type: interventional
• Target: 376
• Locations: 1 country
• Sites: 1

Brief Summary

Branch atheromatous disease (BAD) has been reported to contribute to small-vessel occlusion and is associated with a higher possibility of early neurological deterioration (END). Because the pathology of BAD is due to atherosclerosis, the investigators postulate that early intensive medical treatment with dual antiplatelet therapy(DAPT) and high-intensity statin may prevent END and recurrent stroke. The investigators hypothesise that intensive medical therapy can prevent END in BAD using aspirin, clopidogrel and high-intensity statin.

Conditions

Acute Stroke; Dual Antiplatelet Therapy; Statin

Keywords

Branch Atheromatous Disease; Early neurological deterioration; Dual antiplatelet therapy; Statin

Outcome Measures

Primary Outcomes (1)

• The percentage of patients with early neurological deterioration within 7 days and recurrent ischemic stroke within 30 days.

  The early neurological deterioration is defined as an increase of 2 points of NIHSS. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The maximum possible score is 42, with the minimum score being a 0.

  30 days

Secondary Outcomes (5)

• Percentage of patients with favorable functional recovery defined as a mRS ≦1

  90 days

• Percentage of patients with new clinical vascular events

  90 days

• Changes of atherosclerotic plaque

  6 months

• Numbers of moderate to severe bleeding events

  90 days

• Total mortality

  90 days

Study Arms (2)

Intervention group

EXPERIMENTAL

This group will receive dual antiplatelet and high-intensity statin treatment. * Dual antiplatelet treatment: loading of clopidogrel 300mg plus aspirin 300mg, followed by clopidogrel 75 mg/day and aspirin 100 mg/d from day 2 to day 21, and followed by clopidogrel 75 mg/d or aspirin 100 mg/d from day 15 to day 90. * High-intensity statin treatment: Atorvastatin 40-80mg/day or Rosuvastatin 20 mg/day for 90 days.

Drug: Clopidogrel; Drug: Aspirin; Drug: Atorvastatin; Drug: Rosuvastatin

Historical control

ACTIVE COMPARATOR

A historical control group of patients receiving single antiplatelet therapy but no high-intensity statin treatment will be drawn from previous prospective observation studies. Antiplatelet therapy includes aspirin(100-300mg/day) or Clopidopgrel (75mg/day).

Drug: Clopidogrel; Drug: Aspirin

Interventions

Clopidogrel DRUG

300mg loading and 75mg/day from day 2

Historical control; Intervention group

Aspirin DRUG

Aspirin(100-300mg/day)

Historical control; Intervention group

Atorvastatin DRUG

Atorvastatin 40-80mg/day

Intervention group

Rosuvastatin DRUG

Rosuvastatin 20 mg/day.

Intervention group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of ischemic stroke with National Institute of Health Stroke Scale (NIHSS) score of 1-8
• An ischemic lesion on diffuse-weighted imaging located in the MCA perforator, or Heubner's artery territories or vertebro-basilar perforator territories at brain stem.
• Branch atheromatous disease, defined by a visible lesion in three or more axial MRI cuts in the MCA perforator or Heubner's artery territories or infarcts that extended from the basal surface of the brainstem.
• Ability to randomize within 24 hours of time last known free of new ischemic symptoms.
• Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
• Ability to tolerate high intensity medical therapy, including aspirin at a dose of 50-325 mg/day, clopidogrel with 300mg loading and 75mg after day 2 and high-intensity statin(either atorvastatin 40-80mg or rosuvastatin 20 mg/day).
• Pre-stroke mRS≦1

You may not qualify if:

• Age \< 20 years.
• In the judgment of the treating physician
• A candidate for thrombolysis, endarterectomy or endovascular intervention.
• Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event.
• Patients with more than 50% stenosis of the relevant arteries on magnetic resonance angiography (MRA), including intra- or extra-cranial internal carotid artery, middle cerebral artery or basilar artery.
• Patients with high risk of cardioembolic source, such as atrial fibrillation, acute myocardial infarction, severe heart failure or valvular heart disease.
• Other determined stroke etiology, such as vasculitis, shock, antiphospholipid antibody syndrome and etc.
• Gastrointestinal bleed or major surgery within 3 months prior to index event.
• History of nontraumatic intracranial hemorrhage.
• Clear indication for anticoagulation during the study period (deep venous thrombosis, pulmonary embolism or hypercoagulable state).
• Qualifying ischemic event induced by angiography or surgery.
• Severe non-cardiovascular comorbidity with life expectancy \<3 months.
• Contraindication to clopidogrel, aspirin, atorvastatin or rosuvastatin
• Known allergy to clopidogrel, aspirin atorvastatin or rosuvastatin
• Severe renal (serum creatinine \>2 mg/dL) or hepatic insufficiency (INR\>1.2; ALT\>40 U/L or any resultant complication, such as variceal bleeding, encephalopathy, or jaundice)

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Yenchu Huang

Chiayi City, 613, Taiwan

Location

Related Publications (17)

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• Wang C, Yi X, Zhang B, Liao D, Lin J, Chi L. Clopidogrel plus aspirin prevents early neurologic deterioration and improves 6-month outcome in patients with acute large artery atherosclerosis stroke. Clin Appl Thromb Hemost. 2015 Jul;21(5):453-61. doi: 10.1177/1076029614551823. Epub 2014 Sep 23.

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• Chung JW, Cha J, Lee MJ, Yu IW, Park MS, Seo WK, Kim ST, Bang OY. Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging study (STAMINA-MRI Study). J Neurol Neurosurg Psychiatry. 2020 Feb;91(2):204-211. doi: 10.1136/jnnp-2019-320893. Epub 2019 Aug 1.

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  PMID: 21557807 BACKGROUND

• Huang YC, Weng HH, Tsai YH, Lin LC, Lee JD, Yang JT, Pan YT. Early intensive therapy for preventing neurological deterioration in branch atheromatous disease. Ther Adv Neurol Disord. 2025 Jul 24;18:17562864251357274. doi: 10.1177/17562864251357274. eCollection 2025.

  PMID: 40726739 DERIVED

• Huang YC, Tsai YH, Lin LC, Weng HH, Lee JD, Yang JT. Preliminary results on temporal evolution and clinical implications of atherosclerotic plaque in branch atheromatous disease after statin treatment. Ther Adv Neurol Disord. 2024 Sep 18;17:17562864241273902. doi: 10.1177/17562864241273902. eCollection 2024.

  PMID: 39314261 DERIVED

• Huang YC, Lee JD, Weng HH, Lin LC, Tsai YH, Yang JT. Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison. BMJ Open. 2021 Nov 26;11(11):e054381. doi: 10.1136/bmjopen-2021-054381.

  PMID: 34836908 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Clopidogrel; Aspirin; Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: April 1, 2021
• Study Start: March 23, 2021
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)