小剂量重组组织型纤溶酶原激活剂增强脑出血中血凝块的溶解：脑室内出血溶栓试验。
Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial.
机构信息
Sandra and Malcolm Berman Brain & Spine Institute, Department of Neurology, Sinai Hospital of Baltimore, MD, USA.
出版信息
Stroke. 2011 Nov;42(11):3009-16. doi: 10.1161/STROKEAHA.110.610949. Epub 2011 Aug 25.
BACKGROUND AND PURPOSE
Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis.
METHODS
Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups.
RESULTS
Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution.
CONCLUSIONS
Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.
背景与目的
脑出血和脑室出血患者的死亡率据报道为 50%至 80%。我们评估了一种针对这些患者的血凝块溶解治疗策略，涉及死亡率、脑室感染和出血安全性事件，以及其对脑室血凝块溶解率的影响。
方法
在 14 个中心共纳入了 48 名患者，并将其随机分为 3 mg 重组组织型纤溶酶原激活剂（rtPA）治疗组或安慰剂组。比较两组患者的人口统计学特征、严重程度因素、安全性结局（死亡率、感染、出血）和血凝块溶解率。
结果
严重程度因素，包括入院时格拉斯哥昏迷量表评分、脑出血量、脑室出血量和血压，以及不良事件的分布在两组之间基本相同，除了安慰剂治疗组呼吸系统事件的发生率增加。在入院时、外部脑室引流管关闭时或在积极治疗阶段，两组患者的颅内压和脑灌注压差异均不显著。死亡率（rtPA 组为 18%，安慰剂组为 23%）和脑室炎（rtPA 组为 8%，安慰剂组为 9%）的发生率明显低于预期，出血事件仍低于预定的死亡率（23% rtPA；5% 安慰剂，接近统计学显著性；P=0.1）和脑室炎（8% rtPA；9% 安慰剂）的出血事件发生率阈值。rtPA 的中位给药时间为 7.5 天，安慰剂为 12 天。rtPA 对血凝块溶解率有显著的有益影响。
结论
与安慰剂和历史对照相比，低剂量 rtPA 治疗脑出血伴脑室出血具有可接受的安全性。需要进行设计良好的 III 期临床试验（如 CLEAR III）的数据，才能全面评估这种治疗方法。
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