Muehe Anne M, Feng Dan, von Eyben Rie, Luna-Fineman Sandra, Link Michael P, Muthig Travis, Huddleston Amy E, Neuwelt Edward A, Daldrup-Link Heike E
Department of Radiology, Molecular Imaging Program at Stanford (MIPS) and Lucile Packard Children's Hospital, Stanford University, Stanford, CA, USA.
Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
Invest Radiol. 2016 Apr;51(4):221-227. doi: 10.1097/RLI.0000000000000230.
The aim of this study was to assess the safety profile of ferumoxytol as an intravenous magnetic resonance imaging contrast agent in children.
We prospectively evaluated the safety of ferumoxytol administrations as an "off-label" contrast agent for magnetic resonance imaging in nonrandomized phase 4 clinical trials at 2 centers. From September 2009 to February 2015, 49 pediatric patients (21 female and 28 male, 5-18 years) and 19 young adults (8 female and 11 male, 18-25 years) were reported under an investigator-initiated investigational new drug investigation with institutional review board approval, in health insurance portability and accountability act compliance, and after written informed consent of the child's legal representative or the competent adult patient was obtained. Patients received either a single dose (5 mg Fe/kg) or up to 4 doses of ferumoxytol (0.7-4 mg Fe/kg) intravenously, which were approximately equivalent to one third of the dose for anemia treatment. We monitored vital signs and adverse events directly for up to 1 hour after injection. In addition, we examined weekly vitals, hematologic, renal, and liver serum panels for 1 month after injection in over 20 pediatric patients. At fixed time points before and after ferumoxytol injection, data were evaluated for significant differences by a repeated measures linear mixed model.
Four mild adverse events, thought to be related to ferumoxytol, were observed within 1 hour of 85 ferumoxytol injections: 2 episodes of mild hypotension and 1 case of nausea in 65 injections in pediatric patients without related clinical symptoms. One young adult patient developed warmness and erythema at the injection site. All adverse events were self-resolving. No spontaneous serious adverse events were reported. At a dose of 5 mg Fe/kg or lower, intravenous ferumoxytol injection had no clinical relevance or statistically significant effect (P > 0.05) on vital signs, hematological parameters, kidney function, or liver enzymes within 1 month of the injection.
Ferumoxytol was overall well tolerated among 49 pediatric and 19 young adult patients experiencing various tumors or kidney transplants without major adverse events or signs of hematologic and kidney impairment or liver toxicity. Larger studies are needed to determine the incidence of anaphylactic reactions.
本研究旨在评估非达霉素作为静脉磁共振成像造影剂在儿童中的安全性。
我们在2个中心进行的4期非随机临床试验中，前瞻性评估了非达霉素作为磁共振成像“未标明用途”造影剂的安全性。2009年9月至2015年2月，在机构审查委员会批准、符合《健康保险流通与责任法案》规定并获得儿童法定代表人或成年患者书面知情同意后，49名儿科患者（21名女性和28名男性，5 - 18岁）和19名青年成人（8名女性和11名男性，18 - 25岁）在研究者发起的新药研究中被纳入。患者静脉注射单剂量（5 mg铁/千克）或多达4剂非达霉素（0.7 - 4 mg铁/千克），这大约相当于贫血治疗剂量的三分之一。注射后我们直接监测生命体征和不良事件长达1小时。此外，我们在20多名儿科患者注射后1个月每周检查生命体征、血液学、肾脏和肝脏血清指标。在非达霉素注射前后的固定时间点，通过重复测量线性混合模型评估数据的显著差异。
在85次非达霉素注射的1小时内观察到4起被认为与非达霉素相关的轻度不良事件：在65次儿科患者注射中，2次出现轻度低血压，1例出现恶心但无相关临床症状。1名青年成人患者在注射部位出现温热和红斑。所有不良事件均自行缓解。未报告自发的严重不良事件。在剂量为5 mg铁/千克或更低时，静脉注射非达霉素在注射后1个月内对生命体征、血液学参数、肾功能或肝酶无临床相关性或统计学显著影响（P > 0.05）。
在49名儿科患者和19名青年成人患者（患有各种肿瘤或接受肾脏移植）中，非达霉素总体耐受性良好，未出现重大不良事件或血液学和肾脏损害迹象或肝毒性。需要进行更大规模的研究来确定过敏反应的发生率。
