Study of the Efficacy, Safety and Tolerability of Low Molecular Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients With Embolic Stroke Due to Atrial Fibrillation
试验速览
- 阶段
- 2 期
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- mortality
研究概览
简要总结
Patients with Atrial fibrillation (AF) make a unique group of ischemic stroke, mostly caused by emboli from the left atrial appendage. Oral anticoagulation (Warfarin) is recommended for prevention of recurrent embolic stroke but it takes several days to reach a therapeutic international normalized ratio (INR : 2.5) so bridging therapy with a short acting intravenous anticoagulant is recommended until therapeutic INR level is reached. A common strategy is to use intravenous unfractionated heparin (UFH) until a standard activated partial thromboplastin time (aPTT) is reached and then initiating warfarin. Another strategy is to use subcutaneous (SQ) injection of a low-molecular-weight heparin (LMWH) eg. Enoxaparin.
The investigators will compare LMWH and UFH, focusing on risk of new stroke and mortality rate.
METHOD: This study is randomized controlled trial that will be performed in 80 patients ages between 18 and 75 with confirmed acute ischemic stroke purely due to AF who will be hospitalized in Shiraz Medical University affiliated teaching hospitals. Patients will be randomly assigned in two groups. A brain CT will be done to confirm the absence of intracranial hemorrhage and to assess the size of cerebral ischemia.
First group will receive 1 mg of enoxaparin (Clexane, Sanofi, Paris) per kilogram of body weight SQ every 12 hour with warfarin 5mg orally everyday and both drugs will be continued until the target INR level (2.5) is reached then clexane will be discontinued.
The second group will receive continuous UFH infusion 1000 unit per hour and then the dose will be adjusted to maintain a therapeutic aPTT (two times to baseline) level then warfarin will be started (5 mg everyday).
The investigators will follow patients in both groups until target INR will be achieved (2.5) and after that clexane and UFH will be discontinued. Adverse events will be assessed in both groups for three months.
Data will be analyzed with Statistical Package for the Social Sciences (SPSS) version 15 and Chi-square statistics.
Main outcome of our study will be evaluation of new stroke, mortality, central nervous system (CNS) hemorrhage, major bleeding, drop out and other unwanted side effects in first week and three months after stroke.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
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
- 是
入选标准
- •confirmed diagnosis of acute ischemic stroke purely due to AF
- •AF confirmed by ECG or 24 hour holter monitoring
- •patients who need initiation of anticoagulation for prevention of recurrent stroke
排除标准
- •ages less than 18 or more than 75
- •no cooperation
- •CNS hemorrhage
- •major bleeding
- •infarction size of more than one third of middle cerebral artery territory
- •National Institutes of Health Stroke Scale (NIHSS) more than 20
- •hypersensitivity to IV UFH or LMWH
- •no informed consent
- •other causes for stroke except AF
- •pregnancy
- •breast feeding
- •uncontrolled hypertension (BP more than 220/120)
- •renal, hepatic, respiratory or cardiac failure
- •myocardial infarction
- •infectious endocarditis
- •vasculitis
- •dissection
研究组 & 干预措施
Low molecular-weight heparin
these patients will receive 1 mg of enoxaparin (clexane) per kilogram of body weight subcutaneous every 12 hour with warfarin 5mg QD and both drugs will be continued until the target INR level (2.5) is reached then clexane will be discontinued.
干预措施: Enoxaparin (Drug)
unfractionated heparin
This group will receive continuous intravenous unfractionated heparin sodium infusion 1000 unit per hour initially and then the dose will be adjusted to maintain a therapeutic aPTT level (two times to baseline) then warfarin will be started (5 mg QD).
干预措施: Heparin (Drug)
结局指标
主要结局
mortality
时间窗: up to the 3 months of follow-up
all death cases are included but only mortality due to cerebrovascular accident are considered.
ischemic stroke
时间窗: up to the 3 months of follow-up
Ischemic strokes are those that are caused by interruption of the blood supply
hemorrhagic stroke
时间窗: up to the 3 months of follow-up
hemorrhagic strokes are the ones which result from rupture of a blood vessel or an abnormal vascular structure.
次要结局
- symptomatic CNS hemorrhage(up to the 3 months of follow-up)
- Non-CNS hemorrhage(up to the 3 months of follow-up)
- asymptomatic CNS_hemorrhage(up to the 3 months of follow-up)
- time to reach target INR(average time 7 to 10 days (it is variable between individuals))
- tolerability of drugs(participants will be followed for the duration of hospital stay, an expected average of 1 week)
研究者
Afshin Borhani-Haghighi
Associate Professor of Neurology Shiraz University of Medical Sciences
Shiraz University of Medical Sciences