NXY-059用于急性脑出血的安全性和耐受性：CHANT试验

Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial.

作者信息

Lyden Patrick D, Shuaib Ashfaq, Lees Kennedy R, Davalos Antoni, Davis Stephen M, Diener Hans-Christoph, Grotta James C, Ashwood Tim J, Hardemark Hans-Goren, Svensson Hannah H, Rodichok Larry, Wasiewski Warren W, Ahlberg Gabrielle

机构信息

UCSD Stroke Center, San Diego, CA 92103, USA.

出版信息

Stroke. 2007 Aug;38(8):2262-9. doi: 10.1161/STROKEAHA.106.472746. Epub 2007 Jun 14.

DOI:10.1161/STROKEAHA.106.472746

PMID:17569876

Abstract

BACKGROUND AND PURPOSE

NXY-059 is a free radical-trapping neuroprotectant developed for use in acute ischemic stroke. To facilitate prompt administration of treatment, potentially before neuroimaging, we investigated the safety of NXY-059 in patients with intracerebral hemorrhage (ICH).

METHODS

We randomized 607 patients within 6 hours of acute ICH to receive 2270 mg intravenous NXY-059 over 1 hour and then up to 960 mg/h over 71 hours, or matching placebo, in addition to standard care. The primary outcome was safety: the mortality and the frequency of adverse events, and the change from baseline for a variety of serum, imaging, and electrophysiological measurements. We also studied the overall distribution of disability scores on the modified Rankin Scale (mRS) and the Barthel index.

RESULTS

We treated 300 patients with NXY-059 and 303 with placebo. Treatment groups were well matched for prognostic variables including Glasgow Coma Scale, risk factors, and age. The mean National Institute of Health Stroke Scale score on admission was 14 in both groups. The baseline hemorrhage volume was 22.4+/-20.1 mL in the NXY-059 group and 23.3+/-22.8 mL in the placebo group (mean+/-SD). Most hemorrhages were related to hypertension or anticoagulant use. Mortality was similar in both groups: 20.3% for NXY-059 and 19.8% for placebo-treated patients. The proportion of patients who experienced an adverse event was the same for both groups, whereas for serious adverse events the proportion was slightly higher in the NXY-059 group. However, no pattern emerged to indicate a safety concern. Serum potassium fell transiently in both groups, lower in the NXY-059 group. There were no differences in 3-month function, disability, or neurological deficit scores. The odds ratio for an improved outcome in 3-month mRS scores in the NXY-059 group was 1.01 (95% CI 0.75, 1.35).

CONCLUSIONS

NXY-059 given within 6 hours of acute ICH has a good safety and tolerability profile, with no adverse effect on important clinical outcomes.

摘要

背景与目的

NXY - 059是一种开发用于急性缺血性卒中的自由基捕获神经保护剂。为便于在可能进行神经影像学检查之前迅速给予治疗，我们研究了NXY - 059在脑出血（ICH）患者中的安全性。

方法

我们将607例急性ICH发病6小时内的患者随机分组，一组在1小时内静脉给予2270 mg NXY - 059，然后在71小时内以高达960 mg/h的速度给药，另一组给予匹配的安慰剂，两组均接受标准治疗。主要结局指标为安全性：死亡率、不良事件发生率以及各种血清学、影像学和电生理测量指标相对于基线的变化。我们还研究了改良Rankin量表（mRS）和Barthel指数上残疾评分的总体分布情况。

结果

我们对300例患者给予NXY - 059治疗，303例给予安慰剂治疗。治疗组在包括格拉斯哥昏迷量表、危险因素和年龄等预后变量方面匹配良好。两组入院时美国国立卫生研究院卒中量表平均评分均为14分。NXY - 059组基线出血量为22.4±20.1 mL，安慰剂组为23.3±22.8 mL（均值±标准差）。大多数出血与高血压或抗凝药物使用有关。两组死亡率相似：NXY - 059组为20.3%，安慰剂治疗组为19.8%。两组发生不良事件的患者比例相同，而严重不良事件比例在NXY - 059组略高。然而，未发现表明存在安全问题的模式。两组血清钾均短暂下降，NXY - 059组下降幅度更大。3个月时的功能、残疾或神经功能缺损评分无差异。NXY - 059组3个月时mRS评分改善的优势比为1.01（95%可信区间0.75，1.35）。