Safety and Tolerability of Ultrasmall Superparamagnetic Iron Oxide Contrast Agent Comprehensive Analysis of a Clinical Development Program
Safety and Tolerability of Ultrasmall Superparamagnetic Iron Oxide Contrast Agent Comprehensive Analysis of a Clinical Development Program
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DOI：
10.1097/rli.0b013e3181a0068b
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发表时间：
2009-06-01
影响因子：
6.7
通讯作者：
Bonnemain, Bruno
中科院分区：
文献类型：
--
作者：
Bernd, Hamm;De Kerviler, Eric;Bonnemain, Bruno
背景资料：由于其细胞摄取模式，ferumoxtran-10可能用于多种疾病的成像（例如，动脉粥样化、多发性硬化、中风、肾移植排斥、肾小球肾炎和脑肿瘤，以及转移性和非转移性淋巴结的鉴别）。本文的目的是全面综述ferumoxtran-10的安全性和耐受性，该化合物在临床开发过程中作为超小超顺磁性氧化铁造影剂用于磁共振成像。材料和方法：使用在1777名成人中进行的37项I期至III期临床研究的汇总数据评估了ferumoxtran-10的安全性特征（1663名接受造影剂[1527名患者和136名健康志愿者]，75名接受安慰剂，39名患者入组但未接受研究药物治疗）。ferumoxtran-10组86.3%的患者的不良事件为轻度至中度。ferumoxtran-10组18.2%的患者报告了至少1起研究者认为与研究治疗相关的事件。最常报告的治疗相关不良事件为背痛、瘙痒。头痛和荨麻疹。ferumoxtran-10组共有44例患者（2.6%）报告了76起严重不良事件（SAE）。仅7例SAE（0.42%）被认为与治疗相关（速发过敏反应性休克、胸痛、呼吸困难、皮疹、血氧饱和度降低和2例低血压）。有12例死亡，其中只有1例（速发过敏反应性休克）被认为与ferumoxtran-10有关，ferumoxtran-10通过推注未稀释产品给药，这是一种不再推荐的给药方式。结果在高风险组的患者，包括老年人和那些肝，肾或心血管疾病似乎没有表现出特殊的临床问题，在这些groups.Conclusions的原因：迄今为止的临床经验，因此显示ferumoxtran-10是一种耐受性良好的造影剂。
Background: Because of its cellular uptake pattern, ferumoxtran-10 maybe potentially useful for the imaging of a variety of diseases (eg, atheroma, multiple sclerosis, stroke, renal graft rejection, glomerulonephritis and brain tumors, in addition to differentiation of metastatic and nonmetastatic lymph nodes). The aim of this article is to present a comprehensive review of the safety and tolerability of ferumoxtran-10 as reported during clinical development of the compound as an ultrasmall superparamagnetic iron oxide contrast agent for use in magnetic resonance imaging.Materials and Methods: The safety profile of ferumoxtran-10 was assessed using pooled data from 37 phase I to III clinical studies in 1777 adults (1663 received the contrast agent [1527 patients and 136 healthy volunteers], 75 received placebo, and 39 patients were enrolled but did not receive study medication).Results: At (cast one adverse event was reported in 23.2% of patients who received ferumoxtran-10. Adverse events were of mild-to-moderate severity in 86.3% of patients in the ferumoxtran-10 group. At least 1 event considered by the investigator to be related to study treatment was reported in 18.2% of patients in the ferumoxtran-10 group. The most commonly reported treatment-related adverse events were back pain, pruritus. headache, and urticaria. A total of 44 patients (2.6%) in the ferumoxtran-10 group reported 76 serious adverse event (SAE). Only 7 SAEs (0.42%) were considered to be treatment-related (anaphylactic shock, chest pain, dyspnea, skin rash, oxygen saturation decreased, and 2 cases of hypotension). There were 12 deaths, only one of which (anaphylactic shock) was considered to be related to ferumoxtran-10 which was administered by bolus injection of undiluted product, a mode of administration that is no longer recommended. Results in high-risk groups of patients including the elderly and those with hepatic, renal or cardiovascular disease seemed to show no cause for special clinical concern in these groups.Conclusions: Clinical experience to date therefore shows ferumoxtran-10 to be a well tolerated contrast agent.