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

基本信息

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
项目类别：
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&apos 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

项目摘要

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）：该提案是针对未来比较有效性研究（CER）项目的多中心规划赠款，旨在改善依赖输血依赖性的Thalassybia患者的铁负担。在全球范围内，（未移植）thalassymia主要患者的护理标准正在进行中输血疗法以及终身铁螯合。在过去的三十年中，这种疗法的寿命有所改善，但螯合充分性是可变的，死亡的主要原因仍然是心脏铁的过载。通过MRI测量的铁测量简化了总体和心脏铁负担的评估，但是许多患者的螯合状况是次优的。许多因素会影响螯合的充分性，包括输血负担和依从性。螯合剂和剂量方案的选择也是至关重要的因素，但目前“最佳”策略尚不清楚。由于许多原因，这种缺乏知识不适合随机临床试验，例如（a）当有口服螯合剂可用时，患者不愿意将其随机分配给肠胃外疗法，（b）不同国家/地区螯合剂的改变监管批准状态，以及（c）后勤，财务和公司障碍，以支持螯合剂之间和/或螯合剂之间的随机组合治疗方法。 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泰国计划的地点。该项目将以两个具体的目的来完成：目标1是开发框架和基础设施，以针对Thalassexymia Major的多中心国际CER研究。 AIM 2是为计划的R01应用程序提供可行性信息和螯合剂策略的探索性分析。 AIM 2中初始分析的反馈将迭代地用于改善AIM 1物流，以期预期2012年的R01应用程序。