Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage.
Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage.
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DOI：
10.1161/strokeaha.111.617589
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发表时间：
2011-11
期刊：
影响因子：
8.3
通讯作者：
Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators
中科院分区：
文献类型：
--
作者：
Selim M;Yeatts S;Goldstein JN;Gomes J;Greenberg S;Morgenstern LB;Schlaug G;Torbey M;Waldman B;Xi G;Palesch Y;Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators
用铁螯合剂甲磺酸去铁胺（DFO）治疗可改善脑出血（ICH）动物模型的神经功能恢复。我们的目的是评估不同剂量层DFO治疗自发性ICH患者的可行性、安全性和耐受性，并确定未来疗效研究中采用的最大耐受剂量（MTD）。一项使用持续重新评估方法的多中心、I期、剂量探索研究。在ICH发作后18小时内开始静脉输注DFO，连续3天。受试者在90天内接受重复临床评估，并在给药前和给药后进行CT神经成像。20例受试者入组5个剂量层，从7 mg/kg/天开始，以62 mg/kg/天作为MTD结束。中位年龄为68岁（范围：50-90岁）; 60%为男性;入院时中位GCS和NIHSS评分分别为15（5-15）和9（0-39）。脑出血部位为脑叶40%，深部50%，脑干10%;脑室内出血15%。2例受试者（10%）因不良事件停用DFO。6例受试者（30%）发生了12起严重不良事件（SAE），均与药物无关。DFO输注与轻度降血压作用相关。在第-90天时，50%的患者的mRS ≤2，39%的患者的mRS为4-6; 15%的患者死亡。ICH后连续每日输注DFO是可行的，耐受性良好，与严重不良事件或死亡率无关。我们的研究结果奠定了基础，为未来的研究，以评估在ICH的DFO的疗效。
Treatment with the iron chelator, deferoxamine mesylate (DFO), improves neurological recovery in animal models of Intracerebral hemorrhage (ICH). We aimed to evaluate the feasibility, safety, and tolerability of varying dose-tiers of DFO in patients with spontaneous ICH, and to determine the Maximum Tolerated Dose (MTD) to be adopted in future efficacy studies. A multicenter, phase-I, dose-finding study using the Continual Reassessment Method. DFO was administered by an intravenous infusion for 3 consecutive days, starting within 18 hours of ICH onset. Subjects underwent repeated clinical assessments through 90 days, and CT neuroimaging pre- and post-drug administration. Twenty subjects were enrolled into 5 dose tiers, starting with 7 mg/kg/day and ending with 62 mg/kg/day as the MTD. Median age was 68 years (range: 50–90); 60% were men; and median GCS and NIHSS scores on admission were 15 (5–15) and 9 (0–39), respectively. ICH location was lobar in 40%, deep in 50%, and brainstem in 10%; intraventricular hemorrhage was present in 15%. DFO was discontinued due to adverse events in 2 subjects (10%). Six subjects (30%) experienced 12 serious adverse events (SAEs), none were drug-related. DFO infusions were associated with mild blood pressure lowering effects. Fifty percent of patients had mRS ≤2 and 39% had mRS 4–6 on day-90; 15% died. Consecutive daily infusions of DFO after ICH are feasible, well-tolerated, and not associated with excessive SAEs or mortality. Our findings lay the groundwork for future studies to evaluate the efficacy of DFO in ICH.