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（由应用提供）：试验评估螯合疗法2（TACT2）的目的是在糖尿病患者和先前心脏病发作的患者中对TACT1进行务实，有效的复制。该试验的结果将确定二氨基二氨酸四乙酸（NA2EDTA）螯合疗法是否获得了美国食品药物管理局（FDA）的批准，并随后被接受以降低糖尿病患者患冠状动脉疾病（CAD）的主要不良事件的风险。 TACT2如果积极，还将促进对收益机制的研究，并为CAD病理生物学提供新的见解。评估螯合疗法（TACT1）的试验是根据NCCAM和国家心脏肺和血液研究所（NHLBI）的申请的响应而开发的，以解决有关螯合使用范围宽度的担忧，但对安全性或效率没有可靠的数据。对于心脏病学家来说，螯合策略令人惊讶，与静脉内和口服安慰剂相比，多达40种具有静脉内静脉内dipodium disododium eDTA和口服多种纤维素和多层剂量（OMVM）的结合，导致了先前的肌血管疾病的患者，导致了较旧的心血管疾病的患者（MI），较老（MI），MI，MI，MI，MI，MI，MI，MI，MI），MI较早地进行了治疗（MIMI）。 (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 diabeteses (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年NNT 5.5）和总死亡率降低了43％（P = 0.011，5年NNT 12）。 TACT2的三个特定目的是：1）确定糖尿病患者和先前MI的基于螯合的策略是否改善了无事件的生存； 2）确定糖尿病患者的基于螯合的策略是否会降低死亡率； 3）对TACT2螯合策略进行成本效益分析。 TACT2将招募1200名50岁或以上的糖尿病患者，并以前的MI和2.0 mg/dl或更少的血清产生。将随机分配患者（1：1）接受螯合 + OMVM或双安慰剂，然后进行临床活动，直到5年试验结束。主要终点将是全因死亡率的复合物 MI，中风，冠状动脉血运重建和不稳定心绞痛的住院。掩盖治疗作业的临床活动委员会将调整事件。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MI或中风的复合物； （3）安全。