Trial to Assess Chelation Therapy 2 (TACT2) DCC Supplemental Bridge Funding

评估螯合疗法2的试验(TACT2)是一项正在进行的多中心美国-加拿大随机安慰剂试验。 这项对照试验已经招募了1000名心肌梗塞后糖尿病患者，并正在以析因设计进行测试， 40例静脉注射依地特二钠或安慰剂和大剂量口服 复合维生素或口服安慰剂可以显著减少复发的缺血性心脏事件。这项研究已经 已完成登记并寻求额外2.5年的资金，以完成跟踪、收尾、分析和 演示文稿/出版物。此TACT2延续建议由数据的单个应用程序组成 由首席研究员(PI)领导的杜克临床研究所(DCRI)协调中心(DCC) Kevin J.Anstrom博士和Daniel B.Mark MD，分包给临床协调中心(CCC)，地址： 佛罗里达州迈阿密海滩的西奈山医疗中心(Gervasio A.Lamas MD，PI)和有毒金属和 纽约市哥伦比亚大学梅尔曼公共卫生学院生物信息库核心实验室 (Ana Navas-Acien医学博士，PI)DCC及其分包合同将协调所有注册后活动。 需要对TACT2进行此次竞争性续订，以支持完成后续、数据库锁定、分析 研究假设、试验结果的报道、出版和传播 针对此次竞争更新，《TACT2》的CCC/DCC合并的具体目标是： A.确定糖尿病和既往心肌梗死患者的基于螯合治疗的策略是否改善了 无事件生存的主要复合终点； B.确定糖尿病和既往心肌梗死患者的基于螯合治疗的策略是否减少了所有- 致死原因； C.对TACT2螯合战略进行经济分析； D.确定金属螯合疗法是否减少了活动期患者体内的金属负荷 治疗组，并确定治疗效果大小是否在那些 金属负荷较大； 评估OMVM与安慰剂对临床结果的影响； F.为未来的科学问题维护一个包括DNA在内的生物库。 如果TACT2呈阳性，不仅将导致将螯合作用应用于临床实践和临床指南 而且还将为冠状动脉疾病的病理生物学和病因学提供重要的新见解。

The Trial to Assess Chelation Therapy 2 (TACT2) is an ongoing multicenter US-Canada randomized placebo- controlled trial that has enrolled 1000 post-MI patients with diabetes and is testing, in a factorial design, whether 40 intravenous edetate disodium-based infusions or placebo infusions and high-dose oral multivitamins or oral placebo can significantly reduce recurrent ischemic cardiac events. The study has completed enrollment and seeks funding for 2.5 additional years to complete follow-up, closeout, analysis, and presentations/publications. This TACT2 continuation proposal consists of a single application by the Data Coordinating Center (DCC) at the Duke Clinical Research Institute (DCRI) led by Principal Investigators (PI) Kevin J. Anstrom PhD and Daniel B. Mark MD, with subcontracts to the Clinical Coordinating Center (CCC) at Mount Sinai Medical Center in Miami Beach FL (Gervasio A. Lamas MD, PI) and the Toxic Metals and Biorepository Core Laboratory at the Columbia University Mailman School of Public Health in New York City (Ana Navas-Acien MD PhD, PI). The DCC, and its subcontracts, will coordinate all post-enrollment activities. This competitive renewal of TACT2 is required to support completion of follow-up, database lock, analyses of study hypotheses, reporting, publication, and dissemination of trial results The combined CCC/DCC Specific Aims of TACT2 for this competitive renewal are to: a. Determine if the chelation-based strategy in patients with diabetes and prior MI improves the primary composite endpoint of event-free survival; b. Determine if the chelation-based strategy in patients with diabetes and prior MI reduces all- cause mortality; c. Perform an economic analysis of the TACT2 chelation strategy; d. Determine whether the metal chelation regimen reduces body metal burden in the active treatment group, and to determine whether treatment effect size is larger among those with larger metal burden; e. Assess the effect of OMVM vs. placebo on clinical outcomes; f. Maintain a biorepository including DNA for future scientific questions. TACT2, if positive, will not only result in the acceptance of chelation into clinical practice and clinical guidelines but also will provide important novel insights into the pathobiology and etiology of coronary artery disease.