Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage

去铁胺治疗急性脑出血的安全性和耐受性

基本信息

批准号：
7755382
负责人：
Magdy H Selim
金额：
$ 18.42万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-15 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7755382
关键词：
Accounting Acute Address Adopted Adverse effects Adverse event Animals Brain Brain Edema Caucasians Caucasoid Race Cerebral hemisphere hemorrhage Cessation of life Charge Chelating Agents Clinical Research Clinical assessments Complement 3b Consent Consent Forms Data Deferoxamine Deferoxamine Methanesulfonate Deterioration Dose Drug Industry Edema Elements Ensure Ethnic Origin Exhibits Factor VIIa Ferritin Future Gender Issues Generic Drugs Hematoma Hemoglobin Hour Image Intensive Care Intravenous infusion procedures Iron Israel Letters Logistics Manufacturer Name Maximum Tolerated Dose Mediating Medical center Methods Minority Monitor Names Neurologic Neurologist Neuronal Injury Nursing Staff Outcome Patient Recruitments Patients Pharmaceutical Preparations Pharmacy facility Phase Phase II/III Trial Phase III Clinical Trials Play Press Releases Price Procedures Process Public Health Randomized Rattus Recruitment Activity Regimen Reporting Research Research Personnel Research Training Role Safety Serum Site Stroke Symptoms Testing Time Toxic effect Training Woman Work clinical practice disability discount efficacy testing improved neuroprotection novel open label patient population pre-clinical prospective sensitivity training

项目摘要

DESCRIPTION (provided by applicant): Several animal studies show that hemoglobin breakdown and subsequent iron accumulation in the brain play a role in mediating secondary neuronal injury and brain edema after intracerebral hemorrhage (ICH); and that treatment with iron chelators, such as deferoxamine (DFO), provides neuroprotection. Deferoxamine has been extensively used in clinical practice for more than 30 years. It is well-tolerated, inexpensive, and therefore, may be a potential novel therapy to treat patients with ICH. To date, there have been no clinical studies to examine the effects of DFO in patients with ICH. We propose to conduct a prospective, open-label, non-randomized, multiple-tier, dose-finding, multi-center, preliminary, clinical study to evaluate the safety and tolerability of treatment with DFO in patients with ICH. We will test escalating dose-regimens, starting at a dose of 7 mg/kg up to a maximum dose of 125 mg/kg. A Continuous Reassessment Method of dose toxicity will be used to determine escalating dose levels, and the maximal increment increase between dose-tiers will not exceed 25 mg/kg. The drug will be administered as IV infusion daily for 3 consecutive days, starting within 12 hours of stroke symptom onset. Subjects will undergo repeated clinical assessments up to 90 days, and CT imaging pre- and post-drug administration. Our main objectives are: 1) to evaluate the safety and tolerability of varying doses of DFO, by determining the treatment related adverse events, in patients with ICH; and 2) to determine the maximal tolerated dose to be adopted in subsequent phase II/III studies to determine the optimal treatment time window, and duration, and to test the efficacy of DFO in improving outcome after ICH. We hypothesize that DFO is well-tolerated and has minimal serious adverse effects in patients with ICH. This study will afford the opportunity to apply preclinical efficacious strategy to the treatment of ICH, and will allow us to work out the logistics of drug administration, and implementation of standardized procedures needed to guide the planning of future phase II/III trials. The results can potentially bring into account new means to improve the outcome of patients with ICH. ICH is a frequent cause of disability and death. A successful study demonstrating the efficacy of iron-modifying therapy would be of considerable public health significance.

描述（由申请人提供）：几项动物研究表明，血红蛋白分解和随后的脑中的铁积累在介导次生神经元损伤和脑出血后的脑肿瘤中发挥作用；并用铁螯合剂（例如脱氧胺（DFO））处理神经保护作用。脱铁胺已在临床实践中广泛使用了30多年。它具有良好的耐受性，价格便宜，因此可能是治疗ICH患者的潜在新型疗法。迄今为止，尚无临床研究来检查DFO对ICH患者的影响。我们建议进行一项前瞻性，开放标签，非随机，多层，剂量调查，多中心，初步，临床研究，以评估ICH患者对DFO治疗的安全性和耐受性。我们将以7 mg/kg的剂量从最大剂量开始，最大剂量为125 mg/kg。连续重新评估剂量毒性的方法将用于确定剂量水平的升级，并且剂量层之间的最大增量增加不会超过25 mg/kg。该药物将连续每天连续3天作为IV输注，从中风症状发作的12小时开始。受试者将进行长达90天的重复临床评估，并进行CT成像前后的药物。我们的主要目标是：1）通过确定ICH患者的治疗相关的不良事件来评估不同剂量DFO的安全性和耐受性； 2）确定在随后的II/III期研究中采用的最大耐受剂量，以确定最佳的治疗时间窗口和持续时间，并测试DFO在ICH之后改善结果的功效。我们假设DFO耐受性良好，对ICH患者的严重不良影响最小。这项研究将有机会将临床前有效策略应用于ICH的治疗，并使我们能够确定药物管理的后勤工作，并实施指导未来II/III期试验计划所需的标准化程序。结果可能会考虑到改善ICH患者结果的新手段。 ICH是残疾和死亡的经常原因。一项成功证明铁化治疗功效的成功研究将具有相当大的公共卫生意义。