NXY - 059用于急性缺血性卒中。

NXY-059 for acute ischemic stroke.

作者信息

Lees Kennedy R, Zivin Justin A, Ashwood Tim, Davalos Antonio, Davis Stephen M, Diener Hans-Christoph, Grotta James, Lyden Patrick, Shuaib Ashfaq, Hårdemark Hans-Göran, Wasiewski Warren W

机构信息

Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, United Kingdom.

出版信息

N Engl J Med. 2006 Feb 9;354(6):588-600. doi: 10.1056/NEJMoa052980.

DOI:10.1056/NEJMoa052980

PMID:16467546

Abstract

BACKGROUND

NXY-059 is a free-radical-trapping agent that is neuroprotective in animal models of stroke. We tested whether it would reduce disability in humans after acute ischemic stroke.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial involving 1722 patients with acute ischemic stroke who were randomly assigned to receive a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours after the onset of the stroke. The primary outcome was disability at 90 days, as measured according to scores on the modified Rankin scale for disability (range, 0 to 5, with 0 indicating no residual symptoms and 5 indicating bedbound, requiring constant care).

RESULTS

Among the 1699 subjects included in the efficacy analysis, NXY-059 significantly improved the overall distribution of scores on the modified Rankin scale, as compared with placebo (P=0.038 by the Cochran-Mantel-Haenszel test). The common odds ratio for improvement across all categories of the scale was 1.20 (95 percent confidence interval, 1.01 to 1.42). Mortality and rates of serious and nonserious adverse events were each similar in the two groups. NXY-059 did not improve neurologic functioning as measured according to the National Institutes of Health Stroke Scale (NIHSS): the difference between the two groups in the change from baseline scores was 0.1 point (95 percent confidence interval, -1.4 to 1.1; P=0.86). Likewise, no improvement was observed according to the Barthel index (P=0.14). In a post hoc analysis of patients who also received alteplase, NXY-059 was associated with a lower incidence of any hemorrhagic transformation (P=0.001) and symptomatic intracranial hemorrhage (P=0.036).

CONCLUSIONS

The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. (ClinicalTrials.gov number, NCT00119626.).

摘要

背景

NXY - 059是一种自由基捕获剂，在中风动物模型中具有神经保护作用。我们测试了它是否能降低急性缺血性中风患者的残疾程度。

方法

我们进行了一项随机、双盲、安慰剂对照试验，纳入1722例急性缺血性中风患者，这些患者在中风发作后6小时内被随机分配接受72小时的安慰剂输注或静脉注射NXY - 059。主要结局是90天时的残疾程度，根据改良Rankin残疾量表评分衡量（范围为0至5，0表示无残留症状，5表示卧床不起，需要持续护理）。

结果

在纳入疗效分析的1699名受试者中，与安慰剂相比，NXY - 059显著改善了改良Rankin量表评分的总体分布（ Cochr an - Mantel - Haenszel检验，P = 0.038）。该量表所有类别改善的共同优势比为1.20（95%置信区间为1.01至1.42）。两组的死亡率以及严重和非严重不良事件发生率均相似。根据美国国立卫生研究院卒中量表（NIHSS）测量，NXY - 059并未改善神经功能：两组从基线评分的变化差异为0.1分（95%置信区间为 - 1.4至1.1；P = 0.86）。同样，根据Barthel指数也未观察到改善（P = 0.14）。在对同时接受阿替普酶治疗的患者进行的事后分析中，NXY - 059与任何出血性转化（P = 0.001）和症状性颅内出血（P = 0.036）的发生率较低相关。