Sasaki T, Ohta T, Kikuchi H, Takakura K, Usui M, Ohnishi H, Kondo A, Tanabe H, Nakamura J, Yamada K
Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan.
Neurosurgery. 1994 Oct;35(4):597-604; discussion 604-5. doi: 10.1227/00006123-199410000-00004.
The results of a Phase II clinical trial of intrathecal recombinant tissue-type plasminogen activator for the prevention of vasospasm were reported. The subjects were 53 patients with aneurysmal subarachnoid hemorrhage (SAH), Groups 2 to 4 in Fisher's preoperative computed tomography classification and Grades II to IV in the Hunt-Kosnik classification. Twenty-four hours after surgery, tissue-type plasminogen activator (TD-2061) was intracisternally administered via a catheter (0.1, 0.2, or 0.4 mg, three times daily for 5 days). The clot-dissolving effects assessed as "effective" and "markedly effective" were virtually the same in the 0.1- and 0.2-mg groups (66.7% and 64.3%, respectively) but slightly lower (53.3%) in the 0.4-mg group, suggesting an adequate effect in the 0.1- and 0.2-mg groups. Severe angiographic vasospasm was not observed in any of three groups. No intergroup differences were noted in the incidence of symptomatic vasospasm, low density on computed tomography 1 month after SAH, and functional prognosis. Bleeding complications were noted in 4 patients (7.5%), including 1 case of SAH in the low 0.1-mg group, 2 cases of SAH in the 0.2-mg group, and 1 case of epidural hematoma in the 0.4-mg group. In overall safety rating, 3 cases with increased SAH and 1 case of epidural hematoma were assessed as "safety doubtful." Other minor side effects such as headache and hepatic dysfunction attributed to the effect of other simultaneously used drugs were assessed as "almost safe," and the rate of "almost safe" and "better" for all dose groups was about 90%, suggesting a safe dose level for all groups. These results suggest that repeated intrathecal administration of tissue-type plasminogen activator is useful for preventing vasospasm even in the low dose of 0.1 mg.
有研究报告了鞘内注射重组组织型纤溶酶原激活剂预防血管痉挛的II期临床试验结果。研究对象为53例动脉瘤性蛛网膜下腔出血（SAH）患者，Fisher术前计算机断层扫描分类中的2至4组，Hunt-Kosnik分类中的II至IV级。术后24小时，通过导管向脑池内注射组织型纤溶酶原激活剂（TD - 2061）（0.1、0.2或0.4毫克，每日3次，共5天）。0.1毫克组和0.2毫克组中被评估为“有效”和“显著有效”的溶栓效果几乎相同（分别为66.7%和64.3%），但0.4毫克组略低（53.3%），表明0.1毫克组和0.2毫克组效果良好。三组均未观察到严重的血管造影血管痉挛。症状性血管痉挛的发生率、SAH后1个月计算机断层扫描低密度以及功能预后在组间无差异。4例患者（7.5%）出现出血并发症，包括0.1毫克低剂量组1例SAH、0.2毫克组2例SAH和0.4毫克组1例硬膜外血肿。在总体安全性评级中，3例SAH增加和1例硬膜外血肿被评估为“安全性存疑”。其他轻微副作用，如归因于同时使用的其他药物作用的头痛和肝功能障碍，被评估为“几乎安全”，所有剂量组的“几乎安全”和“较好”率约为90%，表明所有组的剂量水平安全。这些结果表明，即使低至0.1毫克的剂量，重复鞘内注射组织型纤溶酶原激活剂对预防血管痉挛也有效。
