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

August 19, 2024 updated by: Medical University of Graz
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

476

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Medical University of Graz
      • Graz, Austria, 8020
        • Landeskrankenhaus Graz II Standort West
      • Salzburg, Austria, 5020
        • Uniklinikum Salzburg
      • Vienna, Austria, 1030
        • Krankenanstalt Rudolfstiftung
      • Vienna, Austria, 1090
        • Allgemeines Krankenhaus Vienna
    • Burgenland
      • Eisenstadt, Burgenland, Austria, 7000
        • Barmherzige Brüder Eisenstadt
    • Kärnten
      • Klagenfurt, Kärnten, Austria, 9020
        • Klinikum Klagenfurt am Wörthersee
    • Niederösterreich
      • St.Pölten, Niederösterreich, Austria, 3100
        • Universitätsklinikum St. Pölten
    • Oberösterreich
      • Linz, Oberösterreich, Austria, 4021
        • Kepler Universitätsklinikum Linz
    • Salzburg
      • Schwarzach Im Pongau, Salzburg, Austria, 5620
        • Kardinal schwarzenberg Klinikum Schwarzach
    • Vorarlberg
      • Feldkirch, Vorarlberg, Austria, 6800
        • VIVIT Institut am akademischen Lehrkrankenhaus Feldkirch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Empagliflozin
The subjects will receive Empagliflozin 10mg.
Drug: Empagliflozin 10 mg
The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.
Other Names:
  • Jardiance
Placebo Comparator: Placebo Oral Tablet
The subjects will receive placebo.
Drug: Placebo Oral Tablet
The subject will receive Placebo orally once daily for 26 weeks.
Other Names:
  • Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of Nt-proBNP (N-terminales Pro Brain Natriuretic Peptide) Levels
Time Frame: 26 weeks
Difference in the change of nt-proBNP (N terminales pro brain natriuretic peptide) levels between treatment groups from randomization to week 26
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Ejection Fraction
Time Frame: 26 weeks
Difference in the change of ejection fraction between treatment groups from randomization to week 26 Ejection fraction was measured by ultrasound.
26 weeks
Changes in Left Ventricular End-diastolic Volume
Time Frame: 26 weeks
Difference in the change of left ventricular end-diastolic volume from randomization to week 26 (measured by ultrasound)
26 weeks
Duration of Hospital Stay
Time Frame: 30 weeks

Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment.

This outcome measure includes all days of an inpatient stay in a hospital after the initial discharge.
30 weeks
Changes in E/è Ratio From Baseline to Week 26
Time Frame: From Baseline to Week 26

E/E' ratio is a measure of left ventricular filling pressure. The E/e' ratio is a parameter for diastolic function assessment that is frequently used for Heart failure with preserved ejection fraction evaluation.

To derive the E/e´ ratio one must divide the maximum velocity of the E-wave of mitral valve inflow by the maximal velocity of E. In normal individuals the E/e´ ratio is <8. In the presence of diastolic dysfunction / impaired relaxation, e´ will be rather low. In contrast, the E-wave increases with elevated filling pressures. Thus the E/e´ ratio will increase in the presence of diastolic dysfunction. An E/e´ratio >14 is highly suggestive of elevated filling pressures.
From Baseline to Week 26
Changes in Left Ventricular End-systolic Volume (LVESV) From Baselin to Week 26
Time Frame: Baseline to Week 26

End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole.

Left ventricular end-systolic volume (LVESV) was measured at baseline and after 26 weeks by echocardiography.
Baseline to Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Graz

Collaborators

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

Investigators

  • Study Director: Harald Sourij, Assoc.-Prof., Medical University of Graz
  • Principal Investigator: Dirk von Lewinski, Assoc.-Prof., Medical University of Graz

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2017

Primary Completion (Actual)

May 3, 2022

Study Completion (Actual)

May 17, 2022

Study Registration Dates

First Submitted

March 17, 2017

First Submitted That Met QC Criteria

March 22, 2017

First Posted (Actual)

March 23, 2017

Study Record Updates

Last Update Posted (Actual)

August 22, 2024

Last Update Submitted That Met QC Criteria

August 19, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-2017-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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