Saito I, Asano T, Ochiai C, Takakura K, Tamura A, Sano K
Neurol Res. 1983;5(4):29-47. doi: 10.1080/01616412.1983.11739654.
The effect of Nizofenone (Y-9179), a vertebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trials. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors. In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm. Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p less than 0.05). No particular side effect of Nizofenone was observed. Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.
通过一项合作双盲临床试验，研究了椎体保护剂尼唑苯酮（Y-9179）对动脉瘤破裂所致蛛网膜下腔出血（SAH）后迟发性缺血性神经功能缺损的影响。SAH后的迟发性缺血性神经功能缺损与血管痉挛的发生密切相关，任何脑保护剂的有效性取决于药物在缺血性损伤发作前后一段时间内的充分覆盖。因此，该研究设计旨在从这两个因素方面分析尼唑苯酮的效果。在SAH第9天内入院的患者中，立即开始给药并持续5天。当出现迟发性缺血性神经功能缺损时，进行血管造影以确认血管痉挛的存在，然后将给药时间延长5天。该研究招募的100例患者中有10例在揭盲前因发生与血管痉挛无关的严重并发症而被排除。在尼唑苯酮组的42例患者和安慰剂组的48例患者中，分别有25例和29例发生了血管痉挛。因此，尼唑苯酮不能预防血管痉挛。在尼唑苯酮组发生血管痉挛的25例患者中，有13例在血管痉挛发作前后获得了足够的药物覆盖。根据血管痉挛的发生情况，对安慰剂组、尼唑苯酮总组和药物覆盖充足的尼唑苯酮组进行分层。然后比较各组入院后1个月的残疾状态指数以及运动和言语功能等神经功能。在发生血管痉挛的患者中，只有药物覆盖充足的尼唑苯酮组的结果明显优于安慰剂组（p小于0.05）。未观察到尼唑苯酮有特殊的副作用。因此，结果表明，尼唑苯酮可能对SAH后迟发性缺血性神经功能缺损的治疗有用，尽管药物的效果可能会受到给药时间的显著影响。
