Comparative effectiveness of strategies to improve iron chelation in thalassemia

改善地中海贫血铁螯合策略的有效性比较

• 批准号: 8313893
• 负责人: Janet L Kwiatkowski
• 金额: $ 39.28万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8313893
• 关键词: Adherence; Adopted; Adverse effects; Affect; Asians; Canada; Cardiac; Cause of Death; Chelating Agents; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Collaborations; Combined Modality Therapy; Cooley' s anemia; Country; Data; Data Coordinating Center; Data Set; Deferoxamine; Developed Countries; Development; Dose; Evaluation; Feasibility Studies; Feedback; Funding; Future; Goals; Grant; Hemosiderosis; Hereditary Disease; International; Iron; Iron Chelation; Iron Overload; Knowledge; Lead; Life Expectancy; Liver; Liver diseases; Logistics; London; Longevity; Magnetic Resonance Imaging; Maintenance; Measurement; Measures; Methods; National Heart, Lung, and Blood Institute; Observational Study; Oral; Organ; Outcome; Outcome Measure; Patients; Plant Roots; Process; Process Measure; Quality of life; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Refractory; Regimen; Relative (related person); Reporting; Research; Research Infrastructure; Research Methodology; Research Personnel; Research Project Grants; Siderosis; Site; Structure; Syndrome; Testing; Thailand; Thalassemia; Transfusion; Work; Workplace; Writing; arm; base; chelation; clinical research site; cohort; comparative effectiveness; design; effectiveness research; improved; meetings; mortality; research study; standard of care; symposium; young adult

DESCRIPTION (provided by applicant): This proposal is a multicenter planning grant toward a future comparative effectiveness research (CER) project aimed at improving the iron burden of transfusion-dependent thalassemia patients. Worldwide, the standard of care for (non-transplanted) thalassemia major patients is ongoing transfusion therapy plus lifelong iron chelation. This therapy has improved lifespan in thalassemia over the last three decades, but chelation adequacy is variable, and the leading cause of death remains cardiac iron overload. Iron measurements by MRI have simplified assessment of total-body and cardiac iron burden, yet chelation status of many patients is suboptimal. Many factors affect adequacy of chelation, including transfusion burden and adherence. Choice of chelator(s) and dose regimen(s) are also vital factors, but the "optimal" strategy is unclear presently. This lack of knowledge is not amenable to randomized clinical trials for many reasons, e.g. (a) unwillingness of patients to be randomized to parenteral therapy when oral chelators are available, (b) varying regulatory approval status of the chelators in different countries, and (c) logistical, financial and corporate impediments for supporting randomized combination therapy approaches between and/or among chelator brands. The working hypothesis for this proposal is that the Thalassemia Longitudinal Cohort (TLC), an ongoing NHLBI-funded project which captures chelator regimens, iron status, transfusion burden, and measures of adherence and end-organ function for ~400 patients, can form the framework of an observational study that will underlie the planned CER study at TLC sites in the US, Canada, the UK and a new planned site in Thailand. The project will be accomplished in two specific aims: Aim 1 is to develop the framework and infrastructure for a multicenter, international CER study of iron chelation in thalassemia major. Aim 2 is to provide both feasibility information and exploratory analyses of chelator strategies for the planned R01 application. Feedback from initial analyses in aim 2 will be used iteratively to improve Aim 1 logistics in anticipation of an R01 application in 2012.

描述（由申请人提供）：该提案是一项多中心规划拨款，用于未来的比较有效性研究（CER）项目，旨在改善输血依赖性地中海贫血患者的铁负担。在世界范围内，（非移植）重型地中海贫血患者的护理标准是持续输血治疗加上终身铁螯合。在过去的三十年里，这种疗法改善了地中海贫血患者的寿命，但螯合充分性是可变的，死亡的主要原因仍然是心脏铁超负荷。 MRI 铁测量简化了全身和心脏铁负荷的评估，但许多患者的螯合状态并不理想。许多因素影响螯合的充分性，包括输血负担和依从性。螯合剂和剂量方案的选择也是重要因素，但“最佳”策略目前尚不清楚。由于多种原因，这种知识的缺乏不适合随机临床试验，例如(a) 当有口服螯合剂时，患者不愿意随机接受肠外治疗，(b) 不同国家对螯合剂的监管批准状况不同，以及 (c) 支持随机联合治疗方法的后勤、财务和企业障碍/或螯合剂品牌之间。该提案的工作假设是，地中海贫血纵向队列 (TLC) 是一个由 NHLBI 资助的正在进行的项目，该项目记录了约 400 名患者的螯合剂治疗方案、铁状态、输血负担以及依从性和终末器官功能的测量结果。观察性研究框架，该框架将成为计划在美国、加拿大、英国的 TLC 地点和泰国计划的新地点进行的 CER 研究的基础。该项目将实现两个具体目标：目标 1 是为地中海贫血症铁螯合的多中心、国际 CER 研究开发框架和基础设施。目标 2 是为计划的 R01 应用提供可行性信息和螯合剂策略的探索性分析。目标 2 中初步分析的反馈将被迭代地用于改进目标 1 的物流，预计 2012 年将实现 R01 应用。