随机对照试验研究抗血小板治疗联合重组组织型纤溶酶原激活剂溶栓治疗缺血性脑卒中：ARTIS-Trial 的原理和设计。
A randomised controlled trial of antiplatelet therapy in combination with Rt-PA thrombolysis in ischemic stroke: rationale and design of the ARTIS-Trial.
机构信息
Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
出版信息
Trials. 2010 May 12;11:51. doi: 10.1186/1745-6215-11-51.
BACKGROUND
Thrombolysis with intravenous rt-PA is currently the only approved acute therapy for ischemic stroke. Re-occlusion after initial recanalization occurs in up to 34% in patients treated with rt-PA, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolysis and antiplatelet therapy leads to a greater reduction of mortality compared to thrombolysis alone. In patients with acute ischemic stroke, several studies showed that patients already on antiplatelet treatment prior to thrombolysis had an equal or even better outcome compared to patients without prior antiplatelet treatment, despite an increased risk of intracerebral bleeding. Based on the fear of intracerebral haemorrhage, current international guidelines recommend postponing antiplatelet therapy until 24 hours after thrombolysis. Remarkably, prior use of antiplatelet therapy is not a contra-indication for thrombolysis. We hypothesize that antiplatelet therapy in combination with rt-PA thrombolysis will improve outcome by enhancing fibrinolysis and preventing re-occlusion.
METHODS/DESIGN: ARTIS is a randomised multi-center controlled trial with blind endpoint assessment. Our objective is to investigate whether immediate addition of aspirin to rt-PA thrombolysis improves functional outcome in ischemic stroke. Patients with acute ischemic stroke eligible for rt-PA thrombolysis are randomised to receive 300 mg aspirin within 1.5 hours after start of thrombolysis or standard care, consisting of antiplatelet therapy after 24 hours. Primary outcome is poor functional health at 3 months follow-up (modified Rankin Scale 3 - 6).
DISCUSSION
This is the first clinical trial investigating the combination of rt-PA and acute aspirin by means of a simple and cheap adjustment of current antiplatelet regimen. We expect the net benefit of improved functional outcome will overcome the possible slightly increased risk of intracerebral haemorrhage.
TRIAL REGISTRATION
The Netherlands National Trial Register NTR822. The condensed rationale of the ARTIS-Trial has already been published in Cerebrovascular Diseases.
背景
静脉注射重组组织型纤溶酶原激活剂（rt-PA）溶栓治疗是目前缺血性脑卒中唯一被批准的急性治疗方法。接受 rt-PA 治疗的患者中，初始再通后再闭塞的发生率高达 34%，这可能是由血小板激活引起的。在急性心肌梗死中，溶栓联合抗血小板治疗可使死亡率的降低幅度大于单纯溶栓。在急性缺血性脑卒中患者中，几项研究表明，与未接受过抗血小板治疗的患者相比，溶栓前已接受抗血小板治疗的患者的结局相同或甚至更好，尽管颅内出血的风险增加。基于对颅内出血的担忧，目前的国际指南建议将抗血小板治疗推迟至溶栓后 24 小时。值得注意的是，先前使用抗血小板治疗并不是溶栓的禁忌症。我们假设，抗血小板治疗联合 rt-PA 溶栓治疗将通过增强纤维蛋白溶解和防止再闭塞来改善结局。
方法/设计：ARTIS 是一项随机、多中心、对照试验，终点评估为盲法。我们的目的是研究在 rt-PA 溶栓治疗的基础上即刻加用阿司匹林是否能改善缺血性脑卒中患者的功能结局。符合 rt-PA 溶栓治疗条件的急性缺血性脑卒中患者被随机分为两组，一组在溶栓开始后 1.5 小时内接受 300 mg 阿司匹林治疗，另一组接受标准治疗，即 24 小时后接受抗血小板治疗。主要结局是 3 个月随访时的不良功能健康状况（改良 Rankin 量表 3-6 分）。
讨论
这是第一项通过简单且廉价的调整当前抗血小板方案来研究 rt-PA 与急性阿司匹林联合应用的临床试验。我们预计，功能结局改善的净获益将超过颅内出血风险略有增加的可能性。
试验注册
荷兰国家临床试验注册库 NTR822。ARTIS 试验的简要理由已在《脑血管病》上发表。
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