Impact of EMpagliflozin on Cardiac Function and Biomarkers of Heart Failure in Patients With Acute MYocardial Infarction
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 476
- 试验地点
- 11
- 主要终点
- Changes of Nt-proBNP (N-terminales Pro Brain Natriuretic Peptide) Levels
研究概览
简要总结
This study is planned to investigate the impact of Empagliflozin on biomarkers of heart failure in patients with myocardial infarction with and without type 2 diabetes mellitus within 6 months after the event.
详细描述
Type 2 diabetes mellitus (T2DM) is associated with an about two to three-fold increased risk for cardiovascular events as compared to subjects without diabetes.
Sodium-dependent glucose cotransporter 2 (SGLT-2) is mainly expressed in human kidneys and small intestinal cells. In the proximal tubule of the nephron SGLT-2 is responsible for the reabsorption of approximately 90% of the filtrated glucose. Inhibition of SGLT-2 was shown to increase renal glucose excretion and to lower glucose. Subsequently, a number of SGLT-2 inhibitors were developed and are currently approved for the treatment of type 2 diabetes.
Recently, Zinman et al published the results of the Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patient trial (EMPA REG OUTCOME TRIAL) where the cardiovascular impact of a glucose lowering regimen including Empagliflozin as compared to usual glucose control without an SGLT-2 inhibitor was investigated. The trial demonstrated an unexpected reduction in the primary composite endpoint, comprising cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. The reduction was mainly driven by a 38% relative risk reduction in cardiovascular deaths; moreover they demonstrated an impressive 35% relative risk reduction in the secondary endpoint hospitalization for heart failure. Of note, the beneficial effects observed in the Empagliflozin group seem to occur very rapidly after commencing the treatment, as suggested by the early separation of the Kaplan-Meier curves. However, the mechanisms responsible for this finding remain unclear. Diuretic effects with subsequent impact on hemodynamics or potential cardioprotective effects of glucagon, which levels rise under the treatment with SGLT-2 inhibitors and the resulting rise in ketone bodies or a small increase in hematocrit have been suggested.
The aim of our trial is to investigate whether Empagliflozin treatment commenced within 72-h after acute myocardial infarction has an impact on heart failure in subjects with and without diabetes mellitus type 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Myocardial infarction with evidence of significant myocardial necrosis defined as a rise in creatinine kinase >800 U/l and a troponin T-level (or troponin I-level) >10x upper limit of normal (ULN). In addition at least 1 of the following criteria must be the met:
- •Symptoms of ischemia
- •ECG (electrocardiogram) changes indicative of new ischemia (new ST-T changes or new LBBB)
- •Imaging evidence of new regional wall motion abnormality
- •18 - 80 years of age
- •Informed consent has to be given in written form
- •estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m2
- •Blood pressure before first drug dosing: Riva Rocci (RR) systolic >110 mmHg
- •Blood pressure before first drug dosing: Riva Rocci (RR) diastolic >70 mmHg
- •≤72h after myocardial infarction (after the performance of a coronary angiography)
排除标准
- •Any other form of diabetes mellitus than type 2 diabetes mellitus, history of diabetic ketoacidosis
- •Blood potential hydrogen (pH) < 7,32
- •Known allergy to SGLT-2 inhibitors
- •Hemodynamic instability as defined by intravenous administration of catecholamine, calcium sensitizers or phosphodiesterase inhibitors
- •>1 episode of severe hypoglycemia within the last 6 months and treatment with insulin or sulfonylurea
- •Females of childbearing potential without adequate contraceptive methods (i.e. sterilization, intrauterine device, vasectomized partner; or medical history of hysterectomy)
- •Acute symptomatic urinary tract infection (UTI) or genital infection
- •Patients currently being treated with any SGLT-2 inhibitor or having received treatment with any SGLT-2 inhibitor within the 4 weeks prior to the screening visit
研究组 & 干预措施
Empagliflozin
The subjects will receive Empagliflozin 10mg.
干预措施: Empagliflozin 10 mg (Drug)
Placebo Oral Tablet
The subjects will receive placebo.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Changes of Nt-proBNP (N-terminales Pro Brain Natriuretic Peptide) Levels
时间窗: 26 weeks
Difference in the change of nt-proBNP (N terminales pro brain natriuretic peptide) levels between treatment groups from randomization to week 26
次要结局
- Changes in Ejection Fraction(26 weeks)
- Changes in E/è Ratio From Baseline to Week 26(From Baseline to Week 26)
- Changes in Left Ventricular End-systolic Volume (LVESV) From Baselin to Week 26(Baseline to Week 26)
- Changes in Left Ventricular End-diastolic Volume(26 weeks)
- Duration of Hospital Stay(30 weeks)