Efficacy and Safety of Tirofiban in Patients With Acute Branch Atheromatous Disease (BAD)- Related Stroke (BRANT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 516
- 试验地点
- 45
- 主要终点
- Excellent functional outcome
研究概览
简要总结
Branch atheromatous disease (BAD)-related stroke, characterized by subcortical single infarcts without severe stenosis of the large artery, but with a clear atherosclerotic mechanism, is now regarded as a separate stroke type. BAD is associated with early neurological deterioration and poor prognosis, but is lack of effective therapy. The goal of this randomized controlled trial is to test the efficacy and safety of intravenous tirofiban in patients with acute ischemic stroke caused by branch atheromatous disease. The main question it aims to answer is: Compared with standard antiplatelet therapy based on current stroke guideline, whether tirofiban used in acute phase of BAD could improve the proportion of excellent functional outcome (modified Rankin Scale: 0-1) at 90 days. Researcher will also compare the rate of major bleeding between treatment and control groups.
详细描述
BRANT study is a multicenter, randomized, open label, blinded endpoint, Parallel controlled trial with the primary null hypothesis that, in patients with acute BAD-related stroke, there is no difference in the proportion of excellent outcome in those treated with intravenous Tirofiban compared with those treated with standard antiplatelet therapy based on guideline when subjects are randomized within 48 hours of stroke onset.
The primary objective is to determine whether intravenous tirofiban (a loading dose of 0.4ug/kg/min*30min followed by a maintenance dose of 0.1ug/kg/min*47.5h) is effective in increasing the proportion of excellent functional outcome (mR: 0-1) at 90 days, when initiated within 48 hours of onset. The active comparator is standard antiplatelet therapy based on guideline [ie, 1) aspirin 150-300 mg qd, OR 2) aspirin 100 mg qd plus clopidogrel 75 mg qd] for 48 hours.
Patients with acute BAD-related stroke between 18 and 75 years old, who can be randomized within 48 hours of onset, and meet the BAD Diagnostic Imaging Criteria, will be enrolled. All patients will conduct MRI before randomization.
Subjects will be randomized 1:1 (Tirofiban: Standard antiplatelet therapy). The subjects' eligibility will be assessed by site investigator prior to accessing the Randomization Module, which is generated via the dynamic block randomization method. Only certified and trained personnel can access the randomization website, who will get the information of treatment (ie, Tirofiban or standard antiplatelet therapy) after the subject has be determined eligible.
The treatment period is 48 hours for both study groups. A total of 516 eligible patients will be enrolled. Each participant will be followed for 90 days from randomization. The primary outcome will be assessed by well-trained senior neurologists blinded to the treatment. All the clinical and safety events will be re-examined by the Clinical Event Committee (CEC), who are blinded during all procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Our study is an open label, blinded endpoint trail. The primary outcome should be measured in a blinded manner, and the qualified evaluator is defined as: 1) Attending neurologists or above; 2) Complete the training for mRS score before the initiation of patient enrollment; 3) Blind to the antiplatelet treatment of the participants; and 4) Sign the evaluation when it is completed, and inform the other investigators of the results. All the clinical and safety events will be re-examined by the independent Clinical Event Committee (CEC), who are blinded during all procedures.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18-75 years old
- •Acute ischemic stroke
- •Time from onset to randomization ≤48h; if onset time is unknown, time from last known well to randomization ≤48h
- •Meet the following BAD Diagnostic Imaging Criteria
- •DWI infarcts: single (isolated) deep (subcortical) infarcts;
- •The culprit arteries are either Lenticulostriate artery (LSA) or Paramedian pontine artery (PPA), and the infarct lesion on DWI conforms to one of the following characteristics (A/B): A. LSA: 1) "Comma-like" infarct lesions with "Fan-shaped" extension from bottom to top in the coronal plane; or 2) ≥ 3 layers (layer thickness 5-7 mm) on axial DWI brain images; B. PPA: The infarct lesion extends from the deep pons to the ventral pons on the axial DWI brain images;
- •No more than 50% stenosis on the parent artery of the criminal artery (i.e. corresponding basilar or middle cerebral artery) (Confirmed by magnetic resonance angiography [MRA] or computed tomography angiography [CTA] or digital substraction angiography [DSA]).
- •Singed informed consent by the patient or legally authorized representatives.
排除标准
- •Transient ischemic attack (TIA)
- •Intracranial hemorrhagic diseases, vascular malformations, aneurysms, brain abscesses, malignant space-occupying lesions, or other non-ischemic intracranial lesions detected by baseline CT/MRI, or MRA/CTA/DSA;
- •Presence of ≥50% stenosis in extracranial artery in tandem relationship ipsilateral to the lesion;
- •Cardiogenic embolism: atrial fibrillation, myocardial infarction, heart valve disease, dilated cardiomyopathy, infective endocarditis, atrioventricular block disease, heart rate less than 50 beats per minute
- •Have received or plan to receive endovascular therapy or thrombolysis after onset;
- •Stroke of other clear causes, e.g., moyamoya disease, arterial dissection, vasculitis, etc.
- •modified Rankin Scale ≥2 before onset
- •Use of tirofiban within 1 week before or after onset
- •Low platelets (<100×10^9 /L), or Prothrombin time >1.3 times of the upper normal limit, or INR >1.5, or other systemic hemorrhagic tendencies such as hematologic disorders
- •Elevation of ALT or AST more than 1.5 times the upper normal limit;
- •Glomerular filtration rate <60 ml/min/1.73m^2
- •Known malignant tumors
- •History of trauma or major surgical intervention within 6 weeks prior to onset
- •History of intracranial hemorrhage
- •Active or recent history(within 30 days prior to onset) of clinical bleeding (e.g., gastrointestinal bleeding)
- •Malignant hypertension (systolic blood pressure >200 mmHg, or diastolic blood pressure >120 mmHg)
- •Life expectancy ≤ 6 months
- •Contraindications of 3 T MRI examination
- •Pregnant or lactating women
- •Have participated in another clinical trial within 3 months prior to the date of informed consent, or are participating in another clinical trial.
研究组 & 干预措施
Standard antiplatelet therapy group
Standard antiplatelet therapy based on Chinese stroke guideline will be administered after randomization for a total duration of 48h, as the two following types: 1) aspirin 150-300 mg qd, or 2) aspirin 100 mg qd plus clopidogrel 75 mg qd. The time for administration of antiplatelet drugs will be determined by the doctor in conjunction with the participants' use of antiplatelet or anticoagulant medication in the 24h prior to randomization, but the drug should be given as soon as possible after randomization.
干预措施: Aspirin tablet (Drug)
Standard antiplatelet therapy group
Standard antiplatelet therapy based on Chinese stroke guideline will be administered after randomization for a total duration of 48h, as the two following types: 1) aspirin 150-300 mg qd, or 2) aspirin 100 mg qd plus clopidogrel 75 mg qd. The time for administration of antiplatelet drugs will be determined by the doctor in conjunction with the participants' use of antiplatelet or anticoagulant medication in the 24h prior to randomization, but the drug should be given as soon as possible after randomization.
干预措施: Clopidogrel tablet (Drug)
Tirofiban group
Intravenous tirofiban will be administered immediately after randomization for a total duration of 48h with a loading dose of 0.4ug/kg/min*30min, followed by a maintenance dose of 0.1ug/kg/min*47.5h.
干预措施: Tirofiban (Drug)
结局指标
主要结局
Excellent functional outcome
时间窗: 90 days
Primary efficacy outcome: Excellent functional outcome is defined as modified Rankin Scale score: 0-1. Modified Rankin Scale, a commonly used scale for measuring the degree of dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. 0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.3 - Moderate disability. Requires some help, but able to walk unassisted.4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Death.
次要结局
- Changes in aspartate aminotransferase(48 hours)
- Changes in direct bilirubin(48 hours)
- Changes in indirect bilirubin(48 hours)
- Changes in concentration of Na(48 hours)
- Changes in the concentration of K(48 hours)
- Changes in the concentration of creatinine(48 hours)
- Changes in the concentration of albumin(48 hours)
- Changes in the urinary occult blood(48 hours)
- Early neurological deterioration(7 days of randomization)
- mRS(7 and 90 days)
- NIHSS score(7 days and 90 days)
- Barthel index score(90 days)
- Ischemic stroke(90 days)
- Stroke(90 days)
- TIA(90 days)
- Composite endpoint(90 days)
- Proportion of Major bleeding(7 days and 90 days)
- Serious adverse events(90 days)
- Adverse events(90 days)
- Changes in hemoglobin(48 hours)
- Changes in the count of red blood cell(48 hours)
- Changes in the count of white blood cell(48 hours)
- Changes in the count of platelets(48 hours)
- Changes in alanine transaminase(48 hours)
- Excellent functional outcome(7 days)
- mRS(7 and 90 days)
- Early neurological deterioration(7 days of randomization)
- NIHSS score(7 days and 90 days)
- Barthel index score(90 days)
- Ischemic stroke(90 days)
- Stroke(90 days)
- TIA(90 days)
- Composite endpoint(90 days)
- Proportion of Major bleeding(7 days and 90 days)
- Serious adverse events(90 days)
- Adverse events(90 days)
- All-cause death(90 days)
- Changes in hemoglobin(48 hours)
- Changes in the count of red blood cell(48 hours)
- Changes in the count of white blood cell(48 hours)
- Changes in the count of platelets(48 hours)
- Changes in alanine transaminase(48 hours)
- Changes in aspartate aminotransferase(48 hours)
- Changes in direct bilirubin(48 hours)
- Changes in indirect bilirubin(48 hours)
- Changes in concentration of Na(48 hours)
- Changes in the concentration of K(48 hours)
- Changes in the fecal occult blood(48 hours)
- Changes in the concentration of creatinine(48 hours)
- Changes in the concentration of albumin(48 hours)
- Changes in the urinary occult blood(48 hours)