Thalassemia Clinical Research Network

描述（由申请人提供）： 这是地中海贫血临床研究网络（TCRN）的五年更新申请。TCRN的使命是加速地中海贫血管理方面的研究。该使命所涵盖的共病包括地中海贫血;以及α地中海贫血：纯合子、血红蛋白H病和HbH/恒定弹簧。该网络由四个美国核心站点、一个数据协调中心、美国几个大型附属临床站点组成，加拿大，英国和几个较小的区域“卫星”网站的核心中心，在与NHLBI的合作协议。TCRN的主要优势包括研究者和研究中心合作规范患者评估和护理的能力;设计，实施和开展具有观察性，干预性和辅助设计的临床试验。考虑到样本量，多中心网络至关重要。初始资助期的一个关键成就是建立和分析TCRN登记处，从中确定试验受试者。该登记处现在包括来自22个地点的800多名患者，包括重型地中海贫血（n=422）、中间型地中海贫血（n=121）、Hb E/重型地中海贫血（n=103）、输血依赖型重型地中海贫血（n=9）、HbH病（n= 105）和HbH/恒定弹簧（n=44）。更新补助金的具体目的是：（一）在地中海贫血护理的关键领域进行干预性临床试验。提出了两项试验。首先，一项随机对照试验，以检查单独使用去铁胺与去铁胺加去铁酮对由于输血铁过载引起的心脏病的影响。第二，精氨酸与安慰剂治疗肺动脉高压的随机试验，肺动脉高压是中间型地中海贫血和其他溶血性疾病的一个重要问题。(II)为地中海贫血小型创新试验的开发、启动和迅速完成提供基础设施。(Ill)提高地中海贫血表型和临床结局的评估，以促进当前和未来的临床试验。这将通过两项研究来实现。地中海贫血纵向队列研究，以及铁相关器官损伤的详细研究，比较心脏，肝脏和胰腺中铁负荷的测量结果与铁相关器官功能障碍的结局。结合拟议的临床试验和进行详细的基因型/表型相关性的能力，这些改进的表型和结果的措施是强大的工具，以提高地中海贫血临床护理的知识，如NIH的2003年主任的路线图所设想的。

DESCRIPTION (provided by applicant): This is a five-year renewal application for the Thalassemia Clinical Research Network (TCRN). TCRN's mission is to accelerate research in the management of thalassemia. Syndromes encompassed by this mission include the ¿ thalassemia: homozygous or compound heterozygous plus Hemoglobin E/¿ thalassemia; and the alpha thalassemia: homozygous, hemoglobin H disease, and HbH/Constant Spring. The network is composed of four core U.S. sites, a data coordinating center, several large affiliated clinical sites in the U.S., Canada, and England, and several smaller regional "satellite" sites to the core centers, in a cooperative agreement with NHLBI. Key strengths of the TCRN include a demonstrated ability of the investigators and sites cooperatively to standardize patient assessment and care; to design, implement and conduct clinical trials with observational, interventional, and ancillary designs. The multicenter network has been crucial due to sample size considerations. A pivotal accomplishment of the initial grant period is the establishment and analysis of the TCRN Registry, from which subjects for trials are identified. The registry now includes over 800 patients from 22 sites, including ¿-thalassemia major (n=422), ¿ -thal intermedia (n=121), Hb E/ ¿ thal (n=103), transfusion-dependent a-thal major (n=9), HbH disease (n=l 05), and HbH/Constant Spring (n=44). The Specific Aims of the renewal grant are: (I) To perform interventional clinical trials in key areas of thalassemia care. Two trials are proposed. First, a randomized, controlled trial to examine the effect of deferoxamine alone v. deferoxamine plus deferiprone, on cardiac disease due to transfusional iron overload. Second, a randomized trial of arginine v. placebo for pulmonary hypertension, an important problem in thalassemia intermedia and other hemolytic states. (II) To provide an infrastructure for development, launch, and prompt completion of small, innovative trials in thalassemia. (Ill) To improve assessment of phenotype and clinical outcomes in thalassemia, in order to facilitate current and future clinical trials. This will be accomplished by two studies. The Thalassemia Longitudinal Cohort study, as well as a detailed study of iron-related organ damage, comparing measures of iron burden in the heart, liver and pancreas, to outcomes of iron-related organ dysfunction. Combined with the proposed clinical trials and the ability to perform detailed genotype/phenotype correlations, these improved phenotype and outcome measures are powerful tools to enhance knowledge about thalassemia clinical care, as envisioned by the NIH's 2003 Director's Roadmap.