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

Acute Myocardial Infarction Clinical Trial

— EMMY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03087773
• Other study ID #: HS-2017-01
• Status: Completed
• Phase: Phase 3
• Start date: May 11, 2017
• Est. completion date: May 17, 2022

Study information

• Verified date: May 2022
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 EMPA-REG-OUTCOME (Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patient) 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 476
• Est. completion date: May 17, 2022
• Est. primary completion date: May 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 ULN (upper limit of normal). 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. eGFR (glomerular filtration rate) > 45 ml/min/1.73m2

5. Blood pressure before first drug dosing: RR systolic >110 mmHg

6. Blood pressure before first drug dosing: 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 pH (potential hydrogen) < 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

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Heart Failure
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Empagliflozin 10 mg
The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.
• Placebo Oral Tablet
The subject will receive Placebo orally once daily for 26 weeks.

Locations

Country	Name	City	State
Austria	Barmherzige Brüder Eisenstadt	Eisenstadt	Burgenland
Austria	VIVIT Institut am akademischen Lehrkrankenhaus Feldkirch	Feldkirch	Vorarlberg
Austria	Landeskrankenhaus Graz II Standort West	Graz
Austria	Medical University of Graz	Graz
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt	Kärnten
Austria	Kepler Universitätsklinikum Linz	Linz	Oberösterreich
Austria	Uniklinikum Salzburg	Salzburg
Austria	Kardinal schwarzenberg Klinikum Schwarzach	Schwarzach Im Pongau	Salzburg
Austria	Universitätsklinikum St. Pölten	St.Pölten	Niederösterreich
Austria	AKH Vienna	Vienna
Austria	Krankenanstalt Rudolfstiftung	Vienna

Sponsors (12)

Lead Sponsor	Collaborator
Medical University of Graz	Barmherzige Brüder Eisenstadt, Hospital Rudolfstiftung, Johannes Kepler University of Linz, Kardinal Schwarzenberg Klinikum Schwarzach St. Veit, Klinikum Klagenfurt am Wörthersee, Landesklinikum Sankt Polten, Landeskrankenhaus Feldkirch, Landeskrankenhaus II Graz West, Medical University of Vienna, Paracelsus Medical University, United Arab Emirates University

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change of nt-proBNP levels	Difference in the change of nt-proBNP levels between treatment groups from randomization to week 26	26 weeks
Secondary	changes of ejection fraction	Difference in the change of ejection fraction between treatment groups from randomization to week 26	26 weeks
Secondary	changes of ejection fraction	Difference in the change of ejection fraction between treatment groups from randomization to week 6	6 weeks
Secondary	changes of left ventricular diastolic function	Difference in the change of left ventricular diastolic function from randomization to week 26	26 weeks
Secondary	changes of left ventricular diastolic function	Difference in the change of left ventricular diastolic function from randomization to week 6	6 weeks
Secondary	changes of nt-proBNP levels	Difference in the change of nt-proBNP levels between treatment groups from randomization to week 6	6 weeks
Secondary	changes of HbA1c	Difference in the change of HbA1c between treatment groups from randomization to week 26 (in subjects with known diabetes mellitus Type 2)	26 weeks
Secondary	changes of body weight	Difference in the change of body weight between treatment groups from randomization to week 6	6 weeks
Secondary	changes of body weight	Difference in the change of body weight between treatment groups from randomization to week 26	26 weeks
Secondary	changes of blood beta-hydroxybutyrate levels	Difference in the change of blood beta-hydroxybutyrate levels between the treatment groups from randomization to week 6	6 weeks
Secondary	changes of blood beta-hydroxybutyrate levels	Difference in the change of blood beta-hydroxybutyrate levels between the treatment groups from randomization to week 26	26 weeks
Secondary	number of hospital re-admissions due to heart failure	Difference in the number of hospital re-admissions due to heart failure between the treatment groups	30 weeks
Secondary	number of hospital re-admissions for any cause	Difference in the number of hospital re-admissions for any cause between the treatment groups	30 weeks
Secondary	duration of hospital stay	Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment	30 weeks