Trial to Assess Chelation Therapy 2- TACT2 CCC

评估螯合疗法 2- TACT2 CCC 的试验

基本信息

批准号：
9181934
负责人：
GERVASIO A LAMAS
金额：
$ 6.43万
依托单位：
MOUNT SINAI MEDICAL CENTER (MIAMI BEACH)
依托单位国家：
美国
项目类别：
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/9181934
关键词：
Acids Address Adverse event Age Age-Years Alternative Medicine Applications Grants Area Arterial Fatty Streak Atherosclerosis Award Calcium Cardiology Cardiovascular Diseases Cardiovascular system Chelation Therapy Clinical Clinical Research Complex Confidence Intervals Congresses Coronary Coronary Arteriosclerosis Cost Effectiveness Analysis Creatinine Data Data Coordinating Center Diabetes Mellitus Diamines Disease-Free Survival Doctor of Philosophy Double-Blind Method Economics Edetic Acid Enrollment Ethylenes Event Excision Grant Health Health Food Hospitalization Infusion procedures Intravenous Link Mainstreaming Masks Medical Medical center Multivitamin Myocardial Infarction National Center for Complementary and Alternative Medicine National Heart, Lung, and Blood Institute Oral Patients Placebos Policies Policy Making Prevention Principal Investigator Public Health Recurrence Reporting Request for Applications Research Research Institute Risk Safety Sample Size Serum Stroke Subgroup Testing Time United States Food and Drug Administration United States National Institutes of Health Unstable angina abstracting adjudicate base chelation clinical investigation clinical practice cost design diabetic patient evidence base hazard improved insight member mortality novel randomized placebo controlled trial response

项目摘要

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 TACT1 的实用且有效的复制。该试验的结果将确定乙烯二钠是否有效。二胺四乙酸 (Na2EDTA) 螯合疗法获得美国食品和药物管理局 (FDA) 的批准，随后被接受用于降低患者因冠状动脉疾病 (CAD) 发生主要不良事件的风险TACT2 如果呈阳性，还将促进对 CAD 的益处机制的研究，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 的申请请求而开发的。和国家心肺和血液研究所 (NHLBI) 解决了人们对螯合剂使用广泛的担忧，但没有关于安全性或有效性的可靠数据，令心脏病专家感到惊讶的是，螯合剂策略，联合使用。与静脉注射和口服安慰剂相比，静脉注射 EDTA 二钠加口服多种维生素和多种矿物质 (OMVM) 40 次，可显着缩短 50 岁或以上既往心肌梗塞 (MI) 患者的首次心血管事件复发时间，已接受标准循证医学疗法治疗（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 p<0.001，5 年 NNT 5.5)，总死亡率降低43%（p=0.011，5 年 NNT 12）由于这些发现，以及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 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可以改善糖尿病和既往 MI 患者的无事件生存期；基于螯合的策略可降低糖尿病患者的 MI 死亡率；3) 为了对 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 且血清肌酐为 1 的糖尿病患者。 2.0 mg/dL 或更少的患者将被随机分配 (1:1) 接受螯合 + OMVM 或双安慰剂治疗，并随访临床事件直至 5 年底。试验的主要终点是全因死亡率、复发率的综合终点。心肌梗死、中风、冠状动脉血运重建和不稳定心绞痛住院治疗的主要次要终点将包括：(1) 全因死亡率；(2) 心血管死亡率、复发性心肌梗死的综合死亡率。，或中风；以及（3）安全。