A Randomized, Double-blind, Active-Controlled Trial Comparing the Safety and Efficacy of Aspirin Versus Clopidogrel in Stroke Patients With Glucose-6-phosphate Dehydrogenase Deficiency
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 440
- 试验地点
- 19
- 主要终点
- Proportion of protocol-defined hemolysis.
研究概览
简要总结
Aspirin was reported to induce hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency on some occasions, while still widely uesd for stroke prevention. The SAST trial is designed to evaluate the safety and efficacy of aspirin in patients this enzyme disorder.The primary purpose of the trial is to evaluate the hemolytic effects of a 3-month regimen of aspirin 100mg/d versus a 3-month regimen of clopidogrel 75mg/d.
详细描述
This SAST trial is a prospective, multicenter, randomized, double-blind trial.440 acute ischemic stroke (AIS) patients with G6PD deficiency will be randomized to receive a 3-month regimen of aspirin 100mg/d or clopidogrel 75mg/d. The primary end point is the proportion of protocol-defined hemolysis at 90 days. Protocol-defined hemolysis is defined as one or more of the following conditions: a) Hemoglobin level declined ≥2.5 g/dL from baseline, meanwhile ruling out bleeding events. b) Hemoglobin level declined ≥25% from baseline, meanwhile ruling out bleeding events. c) Clinically relevant hemolytic events, could manifested as fatigue, back pain, anemia, dark urine and jaundice. The study consists of five visits including the day of randomization, day 4, day10±3days, day27±3days, day90±7days.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≥40 years(no upper limit)
- •Acute ischemic stroke within 14 days of symptoms onset;
- •Glucose-6-phosphate dehydrogenase deficiency screened in G6PD enzyme activity
- •Had not received aspirin 7 days prior to randomization
- •Informed consent signed
排除标准
- •Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other non-ischemic brain disease, base on head CT or MRI
- •Concomitant infections at the time of randomization
- •mRS>2 prior to the presenting stroke
- •Hemoglobin<10 g/dL prior to randomization
- •Received intravenous thrombolytic therapy or neurointervention treatment before randomization
- •Clear indication for anticoagulation (presumed cardioembolism, eg, atrial fibrillation, prosthetic cardiac valves or suspected endocarditis)
- •Clear indication for dual antiplatelet therapy (eg, minor stroke in 24h (NIHSS ≤3) or endovascular therapy for the indexed event)
- •Anticipated concomitant antiplatelets other than aspirin or clopidogrel (eg, GPIIb/IIIa inhibitors, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol, ticagrelor) and other antithrombotic agents with antiplatelet effects, including traditional/herbal medicine agents.
- •Anticipated concomitant therapy with long-term (>7 days) NSAIDs affecting platelet function
- •Contraindication to clopidogrel or aspirin (1)Known allergic reactions (2)Severe hepatic or renal dysfunction (Severe hepatic dysfunction is defined as serum ALT or AST >2 times the upper limit of the normal group；Severe renal dysfunction is defined as serum creatinine > 1.5 times the upper limit of the normal group) (3)Severe cardiac failure（NYHA class Ⅲ or Ⅳ) (4)Asthma (5)Any history of Hemostatic disorder or systemic bleeding (6)Any history of thrombocytopenia or neutropenia (7)Any history of drug-induced hematologic or hepatic insufficiency (8)Low white blood cell (<2×10^9/L) or platelet count (<100×10^9/L)
- •Any history of thalassemia, autoimmune hemolytic disease, aplastic anemia or other severe hematologic diseases
- •Anticipated concomitant therapy with other contraindicated drugs for G6PD deficiency
- •Severe dysphagia to unable swallow the drugs
- •Concomitant infections and need for antimicrobial therapy
- •Intracranial hemorrhage or gastrointestinal bleed within 3 months, or major surgery within 30 days
- •Stomach tumor or any other malignant tumor
- •Planed surgery or interventional treatment that may affect the study procedure
- •Severe non-cardiovascular comorbidity with life expectancy <3 m
- •Female who is pregnant or lactating
- •Currently receiving an investigational drug or device
- •Inability to understand and/or comply with study procedures due to psychosis, cognition impairment or emotion disturbance.
研究组 & 干预措施
Aspirin
Drugs:Aspirin
干预措施: Aspirin (Drug)
Clopidogrel
Drugs:Clopidogrel
干预措施: Clopidogrel (Drug)
结局指标
主要结局
Proportion of protocol-defined hemolysis.
时间窗: 90±5 days.
Protocol-defined hemolysis is defined as one or more of the following conditions: a) Hemoglobin level declined ≥2.5 g/dL from baseline, meanwhile ruling out bleeding events. b) Hemoglobin level declined ≥25% from baseline, meanwhile ruling out bleeding events. c) Clinically relevant hemolytic events, could manifested as fatigue, back pain, anemia, dark urine and jaundice, adjudicated by the adjudication committee ultimately.
次要结局
- Change in reticulocyte.(4 days,10±3 days,27±3 days and 90±5 days.)
- Proportion of major bleed (GUSTO definition).(90±5 days.)
- Change in unconjugated bilirubin and total bilirubin.(4 days,10±3 days,27±3 days and 90±5 days.)
- Change in lactic dehydrogenase.(4 days,10±3 days,27±3 days and 90±5 days.)
- Overall mortality.(90±5 days.)
- Health related quality of life, assessed by EuroQoL-5 Dimensions questionnaire(90±5 days.)
- Change in hemoglobin.(4 days,10±3 days,27±3 days and 90±5 days.)
- Proportion of new clinical vascular events, defined as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death.(90±5 days.)
- Proportion of functional independence defined as modified Rankin Scale score 0-2.(90±5 days.)
- Proportion of functional independence defined as Barthel Index 95-100.(90±5 days.)
- Change in National Institutes of Health Stroke Scale(90±5 days.)
研究者
Jinsheng Zeng, MD, PhD
Professor
First Affiliated Hospital, Sun Yat-Sen University