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

Sponsor

Chang Gung Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04824911

Collaborator

(none)

424

Enrollment

Location

Arms

64.2

Anticipated Duration (Months)

6.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Stroke Dual Antiplatelet Therapy Statin	Drug: Clopidogrel Drug: Aspirin Drug: Atorvastatin Drug: Rosuvastatin	Phase 2

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:

have a clinical diagnosis of ischemic stroke;
National Institute of Health Stroke Scale (NIHSS) score of 1-8;
an ischemic lesion on diffuse-weighted imaging located in the middle cerebral artery(MCA) perforator, Heubner's artery or vertebrobasilar perforator territories;
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.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

424 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Early Intensive Medical Therapy for the Prevention of Early Neurological Deterioration in Branch Atheromatous Disease

Actual Study Start Date :

Mar 23, 2021

Anticipated Primary Completion Date :

Feb 28, 2024

Anticipated Study Completion Date :

Jul 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention group 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 300mg loading and 75mg/day from day 2 Drug: Aspirin Aspirin(100-300mg/day) Drug: Atorvastatin Atorvastatin 40-80mg/day Drug: Rosuvastatin Rosuvastatin 20 mg/day.
Active Comparator: Historical control 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 300mg loading and 75mg/day from day 2 Drug: Aspirin Aspirin(100-300mg/day)

Arm

Intervention/Treatment

Experimental: Intervention group

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

300mg loading and 75mg/day from day 2

Drug: Aspirin

Aspirin(100-300mg/day)

Drug: Atorvastatin

Atorvastatin 40-80mg/day

Drug: Rosuvastatin

Rosuvastatin 20 mg/day.

Active Comparator: Historical control

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

300mg loading and 75mg/day from day 2

Drug: Aspirin

Aspirin(100-300mg/day)

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Percentage of patients with favorable functional recovery defined as a mRS ≦1 [90 days]
Defined as a mRS ≦1. The Modified Rankin Scale (mRS) runs from 0-6, running from perfect health without symptoms(score 0) to death(score 6).
Percentage of patients with new clinical vascular events [90 days]
ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death
Changes of atherosclerotic plaque [6 months]
The changes of atherosclerotic plaque was measured by high-resolution MRI initially and 6 months later.
Numbers of moderate to severe bleeding events [90 days]
Total mortality [90 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, with an axial diameter ≦ 20mm.-.
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