Clinical trial NCT04824911: Statin and Dual Antiplatelet Therapy to Prevent Early Neurological Deterioration in Branch Atheromatous Disease
Official title: Early Intensive Medical Therapy for the Prevention of Early Neurological Deterioration in Branch Atheromatous Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Stroke
Dual Antiplatelet Therapy
Statin
Keywords: Branch Atheromatous Disease
Early neurological deterioration
Dual antiplatelet therapy
Statin
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2021-04-01
Enrollment: 376
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The SATBRAD study is a single-centre, prospective, open-label, single-group trial with a historical control group of BAD patients treated with single antiplatelet therapy and regular statin treatment in Chang Gung Memorial Hospital in Taiwan.

Eligible participants are as follows:

1. have a clinical diagnosis of ischemic stroke;
2. National Institute of Health Stroke Scale (NIHSS) score of 1-8;
3. an ischemic lesion on diffuse-weighted imaging located in the middle cerebral artery(MCA) perforator, Heubner's artery or vertebrobasilar perforator territories;
4. BAD, defined by a visible lesion in three or more axial MRI cuts in the MCA perforator territory or Heubner's artery territories or infarcts that extended from the basal surface of the brainstem.
5. can receive intensive medical treatment within 24 hours of stroke onset.

Participants in the intervention group will receive DAPT and high-intensity statin treatment. DAPT treatment is administered within 24 hours of stroke onset, with aspirin (300 mg loading and 100 mg/day) and clopidogrel (300mg and 75m/day). Participants will take aspirin and clopidogrel for 21 days and then keep aspirin or clopidogrel alone. High-intensity statin is administered, including atorvastatin 40-80mg or rosuvastatin 20 mg for 3 months.

A historical control group of patients receiving single oral antiplatelet medication and regular statin treatment will be drawn from previous prospective observation studies which were executed since Jan. 2011 to Dec. 2020. The total sample sizes are 147 for intervention group and 277 for control group.

The primary endpoint is the composite of END, defined as an increase of ≧2 points of NIHSS within 7 days, and recurrent ischemic stroke within 30 days.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)
* Hemostatic disorder or systemic bleeding in the past 3 months
* Current thrombocytopenia (platelet count \<100 x109/L) or leukopenia (\<2 x109/L)
* History of drug-induced hematologic or hepatic abnormalities
* Anticipated requirement for long-term (\>7 day) non-study antiplatelet drugs (e.g., dipyridamole, ticagrelor, ticlopidine), or NSAIDs.
* Low-density lipoprotein\<70mg/dl without prior statin treatment in recent one year or within 2 days after recruitment

Primary outcomes:
measure: The percentage of patients with early neurological deterioration within 7 days and recurrent ischemic stroke within 30 days.
timeFrame: 30 days
Secondary outcomes:
measure: Percentage of patients with favorable functional recovery defined as a mRS ≦1
timeFrame: 90 days
measure: Percentage of patients with new clinical vascular events
timeFrame: 90 days
measure: Changes of atherosclerotic plaque
timeFrame: 6 months
measure: Numbers of moderate to severe bleeding events
timeFrame: 90 days
measure: Total mortality
timeFrame: 90 days
Other outcomes:
Locations:
city: Chiayi City
country: Taiwan
facility: Yenchu Huang
Study officials:
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