Trial to Assess Chelation Therapy 2 (TACT2) DCC

评估螯合疗法 2 (TACT2) DCC 的试验

• 批准号: 9144715
• 负责人: Kevin J Anstrom
• 金额: $ 151.2万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9144715
• 关键词: Achievement; Acids; Address; Adverse event; Age; Age-Years; Blinded; Canada; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chelation Therapy; Clinical; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Clinical Trials Design; Companions; Confidence Intervals; Controlled Clinical Trials; Coronary; Coronary Arteriosclerosis; Cost Effectiveness Analysis; Creatinine; Data; Data Coordinating Center; Data Element; Data Quality; Data Set; Development; Diabetes Mellitus; Diamines; Disease-Free Survival; Doctor of Philosophy; Dose; Double-Blind Method; Economics; Edetic Acid; Elements; Enrollment; Ethylenes; Event; Fostering; Health; Health Food; Hospitalization; Infusion procedures; Intravenous; Leadership; Masks; Medical; Medical center; Multivitamin; Multivitamins/Minerals; Myocardial Infarction; National Center for Complementary and Alternative Medicine; National Heart, Lung, and Blood Institute; Oral; Organization and Administration; Outcome; Patients; Placebo Control; Placebos; Principal Investigator; Public Health; Randomized; Recurrence; Request for Applications; Research; Research Institute; Research Personnel; Risk; Safety; Schedule; Serum; Site; Statistical Data Interpretation; Stroke; Subgroup; Supervision; Testing; Time; United States Food and Drug Administration; United States National Institutes of Health; Unstable angina; Work; abstracting; adjudicate; base; chelation; clinical research site; compliance behavior; cost effectiveness; data management; design; diabetic patient; evidence base; experience; follow-up; high risk; improved; insight; meetings; mortality; novel; novel therapeutics; response; study population; tool; trial design

 DESCRIPTION (provided by applicant): The purpose of the Trial to Assess Chelation Therapy 2 (TACT2) is to perform a pragmatic and efficient replication of TACT1 in patients with diabetes and a prior heart attack. The results of this trial will determine whether disodium ethylene diamine tetraacetic acid (Na2EDTA) chelation therapy receives approval from the US Food and Drug Administration (FDA) and is subsequently accepted to reduce the risk of major adverse events from coronary artery disease (CAD) in patients with diabetes. TACT2, if positive, will also promote research into the mechanism(s) of benefits and provide novel insights into the pathobiology of CAD. The Trial to Assess Chelation Therapy (TACT1) was developed in response to a Request for Applications from NCCAM and the National Heart Lung and Blood Institute (NHLBI) to address the concern that chelation use was widespread but there were no reliable data on either safety or efficacy. Surprisingly to cardiologists, the chelation strategy, combination of up to 40 infusions with intravenous disodium EDTA plus oral multivitamins and multiminerals (OMVM) compared with intravenous and oral placebo, led to a significant reduction in the time to first recurrent cardiovascular event in patients with prior myocardial infarction (MI), age 50 or older, already treated with standard evidence based medical therapies (HR 0.74; 95% confidence intervals (CI) 0.57- 0.95; p=0.016. The 5-year number needed to treat (NNT) was 12. In the prespecified subgroup with diabetes (n=633), the results were dramatic: the chelation-based strategy reduced the composite primary clinical endpoint by 51% (HR 0.49, 95%CI (0.33 0.75); p<0.001, 5-year NNT 5.5) and reduced total mortality by 43% (p=0.011, 5-year NNT 12). As a result of these findings, and because of the public health impact of cardiovascular disease and of diabetes, we have been encouraged by the National Institutes of Health (NIH) and the FDA to confirm the results of TACT1. The three Specific Aims of TACT2 are: 1) To determine if the chelation-based strategy in patients with diabetes and prior MI improves event-free survival; 2) To determine if the chelation-based strategy in patients with diabetes and prior MI reduces mortality; 3) To perform a cost-effectiveness analysis of the TACT2 chelation strategy. TACT2 will enroll 1200 diabetic patients 50 years of age or older with a prior MI and a serum creatinine of 2.0 mg/dL or less. Patients will be randomly allocated (1:1) to receive either chelation + OMVM or double placebo and followed for clinical events until the end of the 5 year trial. The primary endpoint will be a composite of all-cause mortality, recurrent MI, stroke, coronary revascularization, and hospitalization for unstable angina. A Clinical Events Committee masked to treatment assignment will adjudicate events. Principal secondary endpoints will include: (1) all-cause mortality; (2) a composite of cardiovascular mortality, recurrent MI, or stroke; and (3) safety.

 描述（由申请人提供）：评估螯合疗法 2 (TACT2) 的试验的目的是在患有糖尿病和既往心脏病发作的患者中进行实用且有效的 TACT1 复制。该试验的结果将确定乙二胺四乙酸二钠（Na2EDTA）螯合疗法是否获得美国食品和药物管理局（FDA）的批准，并随后被接受以降低糖尿病患者冠状动脉疾病（CAD）主要不良事件的风险。 TACT2 如果呈阳性，还将促进对其益处机制的研究，并为 CAD 的病理学提供新的见解。评估螯合疗法的试验 (TACT1) 是应 NCCAM 和国家心肺和血液研究所 (NHLBI) 的申请请求而开发的，旨在解决螯合剂使用广泛但没有可靠的安全性或有效性数据的担忧。令心脏病专家惊讶的是，与静脉注射和口服安慰剂相比，螯合策略（最多 40 次静脉注射 EDTA 二钠加口服多种维生素和多种矿物质 (OMVM) 相结合）显着缩短了既往患有心肌梗塞 (MI)、年龄为 50 岁或以上、已接受标准循证医学疗法治疗的患者的首次心血管事件复发时间 （HR 0.74；95% 置信区间 (CI) 0.57-0.95；p=0.016。需要治疗的 5 年人数 (NNT) 为 12。在预先指定的糖尿病亚组 (n=633) 中，结果非常引人注目：基于螯合的策略将复合主要临床终点降低了 51%（HR 0.49，95%CI (0.33) 0.75）； p<0.001，5 年 NNT 5.5）并将总死亡率降低 43%（p=0.011，5 年 NNT 12）。由于这些发现，并且由于心血管疾病和糖尿病对公共健康的影响，美国国立卫生研究院 (NIH) 和 FDA 鼓励我们确认 TACT1 的结果。 TACT2 的三个具体目标是： 1) 确定基于螯合的策略是否 患有糖尿病和既往心梗的患者可改善无事件生存期； 2) 确定对于患有糖尿病且既往患有心肌梗死的患者，基于螯合的策略是否可以降低死亡率； 3) 对 TACT2 螯合策略进行成本效益分析。 TACT2 将招募 1200 名 50 岁或以上、既往有 MI 且血清肌酐等于或低于 2.0 mg/dL 的糖尿病患者。患者将被随机分配 (1:1) 接受螯合 + OMVM 或双安慰剂治疗，并随访临床事件直至 5 年试验结束。主要终点将是全因死亡率、复发性死亡率的综合终点 心肌梗塞、中风、冠状动脉血运重建以及不稳定心绞痛住院治疗。不知情的临床事件委员会将对事件进行裁决。主要次要终点包括：（1）全因死亡率； (2) 心血管死亡率、复发性心肌梗死或中风的综合； (3)安全。