Palesch Yuko Y, Hill Michael D, Ryckborst Karla J, Tamariz Diego, Ginsberg Myron D
Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, Florida 33101, USA.
Stroke. 2006 Aug;37(8):2107-14. doi: 10.1161/01.STR.0000231389.34701.b5. Epub 2006 Jun 29.
High-dose human albumin (ALB) is robustly neuroprotective in rodent stroke models. A phase I dose-escalation study was conducted to assess the safety of ALB therapy in ischemic stroke. We analyzed the data for preliminary evidence of treatment efficacy.
Eighty-two subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received 25% ALB beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed (range, 0.34 to 2.05 g/kg). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Efficacy outcomes were determined at 3 months. We compared the highest three, putatively therapeutic ALB dose tiers (1.37 to 2.05 g/kg) with the lowest three, presumed subtherapeutic doses (0.34 to 1.03 g/kg) and with historical cohort data derived from the NINDS rt-PA Stroke Study.
After adjusting for the tPA effect, the probability of good outcome (defined as modified Rankin Scale 0 to 1 or NIH Stroke Scale 0 to 1 at 3 months) at the highest three ALB doses was 81% greater than in the lower dose-tiers (relative risk [RR], 1.81; 95% confidence interval [CI], 1.11 to 2.94) and was 95% greater than in the comparable NINDS rt-PA Stroke Study cohort (RR, 1.95; 95% CI, 1.47 to 2.57). The tPA-treated subjects who received higher-dose ALB were three times more likely to achieve a good outcome than subjects receiving lower-dose ALB, suggesting a positive synergistic effect between ALB and tPA.
Our data suggest that high-dose ALB therapy may be neuroprotective after ischemic stroke. These results have led to a multicenter, randomized, placebo-controlled efficacy trial of ALB in acute ischemic stroke-the ALIAS Phase III Trial.
在啮齿动物中风模型中，高剂量人白蛋白（ALB）具有强大的神经保护作用。开展了一项I期剂量递增研究，以评估ALB治疗缺血性中风的安全性。我们分析了数据，以寻找治疗效果的初步证据。
82例急性缺血性中风患者（美国国立卫生研究院卒中量表[NIHSS]评分6分及以上）在中风发作后16小时内开始接受25%的ALB治疗。评估了六个连续的ALB剂量级别（范围为0.34至2.05 g/kg）。42例患者还接受了标准治疗的静脉注射组织纤溶酶原激活剂（tPA）。在3个月时确定疗效结果。我们将最高的三个假定具有治疗作用的ALB剂量级别（1.37至2.05 g/kg）与最低的三个假定为亚治疗剂量（0.34至1.03 g/kg）进行了比较，并与来自美国国立神经疾病和中风研究所rt-PA中风研究的历史队列数据进行了比较。
在调整tPA的影响后，最高的三个ALB剂量组中良好预后（定义为3个月时改良Rankin量表评分为0至1或NIHSS评分为0至1）的概率比低剂量组高81%（相对风险[RR]，1.81；95%置信区间[CI]，1.11至2.94），比美国国立神经疾病和中风研究所rt-PA中风研究中类似队列高95%（RR，1.95；95%CI，1.47至2.57）。接受高剂量ALB治疗的tPA治疗患者实现良好预后的可能性是接受低剂量ALB治疗患者的三倍，这表明ALB与tPA之间存在积极的协同作用。
我们的数据表明，高剂量ALB治疗可能对缺血性中风后具有神经保护作用。这些结果促成了一项关于ALB在急性缺血性中风中的多中心、随机、安慰剂对照疗效试验——ALIAS III期试验。
