STUDY OF THALASSEMIA AND TREATMENT

(改编自申请人的摘要)本研究旨在 比较铁络合剂去铁胺的有效性，当 使用两种不同的途径给药：皮下推注和8- 地中海贫血患者的一小时皮下输液(标准疗法) 少校。虽然到目前为止有几项研究测量了尿铁排泄量 在这两种去铁胺方案中取得的效果，它们的相对有效性 还没有被比较过。尽管去铁胺有效，但它的使用是 并发需要长时间的静脉输液，作为一种 结果，相当大的费用和病人依从性差。因为大多数人 受地中海贫血影响的患者生活在新兴国家，而新兴国家无法 负担得起与输液泵相关的费用，这种救命疗法 只有世界上一小部分地中海贫血患者可以使用。初级阶段 本研究的假设是皮下注射阿司匹林 去铁胺，在12个月内每天服用两次，将减少 或将体内储存的铁的浓度维持在与 每晚8小时皮下输注阿司匹林的患者队列 同一时期的去铁胺。拟议研究的具体目标 要比较的是：每天两次团注的短期疗效，以及 8小时输注去铁胺，通过尿铁排泄和 降低血清铁及其代谢物的毒性部分；相对 这些方案的有效性，通过降低肝铁来确定 专注度；以及患者对这些方案的依从性。初级阶段 这项试验的终点是肝铁浓度，最定量的， 测定体内铁负荷的特异而灵敏的方法 在基线和12个月后，对所有患者进行测定。 如果每天两次团注的有效性被证明是 与传统的去铁胺输注相同，这种新的方案将 为全世界所有地中海贫血患者提供一种经济高效的 方便的替代长时间输注去铁胺的药物，目前 这种救命药物的唯一给药方法。

(Adapted from the applicant's abstract) This research study is designed to compare the effectiveness of the iron-chelating agent deferoxamine, when administered using two different routes: subcutaneous bolus injections, and 8- hour subcutaneous infusions (standard therapy), in patients with thalassemia major. While a few studies to date have measured urinary iron excretion achieved with these two regimens of deferoxamine, their relative effectiveness has not been compared. Despite its effectiveness, the use of deferoxamine is complicated by a requirement for prolonged parenteral infusion and, as a consequence, considerable expense and poor patient compliance. Because most patients affected with thalassemia live in emerging countries which cannot afford this expense associated with infusion pumps, this life-saving therapy is available to a small fraction of the world's thalassemics. The primary hypothesis of this study is that subcutaneous bolus injections of deferoxamine, administered twice daily over a period of 12 months, will reduce or maintain body storage iron at concentrations equivalent to those in a cohort of patients treated with nightly 8-hour subcutaneous infusions of deferoxamine over the same period. The specific aims of the proposed research are to compare: the short-term efficacy of twice-daily bolus injections, and 8-hour infusions of deferoxamine, as determined by urinary iron excretion and reduction in toxic fractions of serum iron and its metabolites; the relative effectiveness of these regimens, as determined by reduction of hepatic iron concentration; and patient compliance with these regimens. The primary endpoint of this trial is hepatic iron concentration, the most quantitative, specific and sensitive method for determining body iron burden, to be determined in each patient at baseline and after 12 months, in all patients. If the effectiveness of twice-daily bolus injections is demonstrated to be equal to that of conventional infusions of deferoxamine, this new regimen will offer to all patients with thalassemia, worldwide, a cost-effective and convenient alternative to prolonged infusions of deferoxamine, currently the only method of administration of this life-saving drug.