Clinical trial NCT03087773: Impact of EMpagliflozin on Cardiac Function and Biomarkers of Heart Failure in Patients With Acute MYocardial Infarction
Official title: Impact of EMpagliflozin on Cardiac Function and Biomarkers of Heart Failure in Patients With Acute MYocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myocardial Infarction
Keywords: Biomarker
Heart failure
SGLT-2 inhibitor
Empagliflozin
Randomized controlled trial
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: United Arab Emirates University
name: Medical University of Vienna
name: Landeskrankenhaus Feldkirch
name: Paracelsus Medical University
name: Hospital Rudolfstiftung
name: Klinikum Klagenfurt am Wörthersee
name: Barmherzige Brüder Eisenstadt
name: Cardinal Schwarzenberg Hospital
name: Johannes Kepler University of Linz
name: Landesklinikum Sankt Polten
name: Landeskrankenhaus II Graz West
First posted: 2017-03-23
Enrollment: 476
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes of Nt-proBNP (N-terminales Pro Brain Natriuretic Peptide) Levels
timeFrame: 26 weeks
Secondary outcomes:
measure: Changes in Ejection Fraction
timeFrame: 26 weeks
measure: Changes in Left Ventricular End-diastolic Volume
timeFrame: 26 weeks
measure: Duration of Hospital Stay
timeFrame: 30 weeks
measure: Changes in E/è Ratio From Baseline to Week 26
timeFrame: From Baseline to Week 26
measure: Changes in Left Ventricular End-systolic Volume (LVESV) From Baselin to Week 26
timeFrame: Baseline to Week 26
Other outcomes:
Locations:
city: Eisenstadt
country: Austria
facility: Barmherzige Brüder Eisenstadt
state: Burgenland
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
state: Kärnten
city: St.Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
state: Niederösterreich
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Linz
state: Oberösterreich
city: Schwarzach Im Pongau
country: Austria
facility: Kardinal schwarzenberg Klinikum Schwarzach
state: Salzburg
city: Feldkirch
country: Austria
facility: VIVIT Institut am akademischen Lehrkrankenhaus Feldkirch
state: Vorarlberg
city: Graz
country: Austria
facility: Landeskrankenhaus Graz II Standort West
city: Graz
country: Austria
facility: Medical University of Graz
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg
city: Vienna
country: Austria
facility: Krankenanstalt Rudolfstiftung
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus Vienna
Study officials:
affiliation: Medical University of Graz
name: Harald Sourij, Assoc.-Prof.
role: STUDY_DIRECTOR
affiliation: Medical University of Graz
name: Dirk von Lewinski, Assoc.-Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: von Lewinski D, Kolesnik E, Tripolt NJ, Pferschy PN, Benedikt M, Wallner M, Alber H, Berger R, Lichtenauer M, Saely CH, Moertl D, Auersperg P, Reiter C, Rieder T, Siller-Matula JM, Gager GM, Hasun M, Weidinger F, Pieber TR, Zechner PM, Herrmann M, Zirlik A, Holman RR, Oulhaj A, Sourij H. Empagliflozin in acute myocardial infarction: the EMMY trial. Eur Heart J. 2022 Nov 1;43(41):4421-4432. doi: 10.1093/eurheartj/ehac494.
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