Impact of EMpagliflozin on Cardiac Function and Biomarkers of Heart Failure in Patients With Acute MYocardial Infarction (EMMY)

Medical University of Graz

Status and phase: Completed; Phase 3

Conditions: Acute Myocardial Infarction

Treatments: Drug: Placebo Oral Tablet; Drug: Empagliflozin 10 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03087773

HS-2017-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 476 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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

2. 18 - 80 years of age

3. Informed consent has to be given in written form

4. estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m2

5. Blood pressure before first drug dosing: Riva Rocci (RR) systolic >110 mmHg

6. Blood pressure before first drug dosing: Riva Rocci (RR) diastolic >70 mmHg

7. ≤72h after myocardial infarction (after the performance of a coronary angiography)

Exclusion criteria

1. Any other form of diabetes mellitus than type 2 diabetes mellitus, history of diabetic ketoacidosis
2. Blood potential hydrogen (pH) < 7,32
3. Known allergy to SGLT-2 inhibitors
4. Hemodynamic instability as defined by intravenous administration of catecholamine, calcium sensitizers or phosphodiesterase inhibitors
5. >1 episode of severe hypoglycemia within the last 6 months and treatment with insulin or sulfonylurea
6. Females of childbearing potential without adequate contraceptive methods (i.e. sterilization, intrauterine device, vasectomized partner; or medical history of hysterectomy)
7. Acute symptomatic urinary tract infection (UTI) or genital infection
8. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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476 participants in 2 patient groups, including a placebo group

Empagliflozin

Active Comparator group

Description:

The subjects will receive Empagliflozin 10mg.

Treatment:

Drug: Empagliflozin 10 mg

Placebo Oral Tablet

Placebo Comparator group

Description:

The subjects will receive placebo.

Treatment:

Drug: Placebo Oral Tablet