Trial to Assess Chelation Therapy 2 (TACT2) DCC

评估螯合疗法 2 (TACT2) DCC 的试验

• 批准号: 9182074
• 负责人: Kevin J Anstrom
• 金额: $ 38.98万
• 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 2016-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9182074
• 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)的试验的目的是在糖尿病和既往心脏病发作的患者中进行实用而有效的TACT1复制。这项试验的结果将决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，并随后被接受用于降低糖尿病患者冠状动脉疾病(CAD)的重大不良事件的风险。如果TACT2呈阳性，也将促进对益处机制(S)的研究，并为冠心病的病理生物学提供新的见解。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)的申请而开发的，以解决人们的担忧，即螯合疗法的使用很广泛，但没有关于安全性或有效性的可靠数据。令心脏病专家惊讶的是，与静脉和口服安慰剂相比，螯合策略结合静脉注射乙二胺四乙酸二钠和口服多种维生素和多种矿物质(OMVM)多达40次，导致已经接受标准循证医学治疗的既往心肌梗死(MI)患者首次复发心血管事件的时间显著减少(HR0.74；95%可信区间0.57-0.95；p=0.016)。在糖尿病(n=633)的预先指定的亚组中，结果是戏剧性的：基于络合的策略将综合主要临床终点降低了51%(HR0.49，95%CI(0.330.75)；p&lt；0.001，5年NNT5.5)，并降低了43%的总死亡率(p=0.011，5年NNT12)。由于这些发现，以及心血管疾病和糖尿病对公众健康的影响，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)确定在糖尿病和既往心肌梗死患者中采用基于螯合的策略是否能提高无事件存活率；2)确定在糖尿病和既往有心肌梗死的患者中采用基于螯合的策略是否能降低死亡率；3)对TACT2的螯合策略进行成本效益分析。TACT2将招募1200名50岁或50岁以上、有心肌梗死史、血清肌酐低于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或双重安慰剂治疗，并跟踪观察临床事件，直到5年试验结束。主要终点将是各种原因造成的死亡率、复发率 心肌梗塞、中风、冠状动脉血运重建和不稳定心绞痛住院。被蒙面进行治疗分配的临床事件委员会将对事件进行裁决。主要次级终点将包括：(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指标；以及(3)安全性。