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

NCT ID: NCT03087773

Last Updated: 2024-08-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

476 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-11

Study Completion Date

2022-05-17

Brief Summary

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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

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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.

Conditions

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Acute Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Empagliflozin

The subjects will receive Empagliflozin 10mg.

Group Type ACTIVE_COMPARATOR

Empagliflozin 10 mg

Intervention Type DRUG

The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.

Placebo Oral Tablet

The subjects will receive placebo.

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

The subject will receive Placebo orally once daily for 26 weeks.

Interventions

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Empagliflozin 10 mg

The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.

Intervention Type DRUG

Placebo Oral Tablet

The subject will receive Placebo orally once daily for 26 weeks.

Intervention Type DRUG

Other Intervention Names

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Jardiance Sugar pill

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United Arab Emirates University

OTHER

Sponsor Role collaborator

Medical University of Vienna

OTHER

Sponsor Role collaborator

Landeskrankenhaus Feldkirch

OTHER

Sponsor Role collaborator

Paracelsus Medical University

OTHER

Sponsor Role collaborator

Hospital Rudolfstiftung

OTHER

Sponsor Role collaborator

Klinikum Klagenfurt am Wörthersee

OTHER

Sponsor Role collaborator

Barmherzige Brüder Eisenstadt

OTHER

Sponsor Role collaborator

Cardinal Schwarzenberg Hospital

OTHER

Sponsor Role collaborator

Johannes Kepler University of Linz

OTHER

Sponsor Role collaborator

Landesklinikum Sankt Polten

OTHER

Sponsor Role collaborator

Landeskrankenhaus II Graz West

OTHER

Sponsor Role collaborator

Medical University of Graz

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Harald Sourij, Assoc.-Prof.

Role: STUDY_DIRECTOR

Medical University of Graz

Dirk von Lewinski, Assoc.-Prof.

Role: PRINCIPAL_INVESTIGATOR

Medical University of Graz

Locations

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Barmherzige Brüder Eisenstadt

Eisenstadt, Burgenland, Austria

Site Status

Klinikum Klagenfurt am Wörthersee

Klagenfurt, Carinthia, Austria

Site Status

Universitätsklinikum St. Pölten

Sankt Pölten, Lower Austria, Austria

Site Status

Kardinal schwarzenberg Klinikum Schwarzach

Schwarzach im Pongau, Salzburg, Austria

Site Status

Kepler Universitätsklinikum Linz

Linz, Upper Austria, Austria

Site Status

VIVIT Institut am akademischen Lehrkrankenhaus Feldkirch

Feldkirch, Vorarlberg, Austria

Site Status

Landeskrankenhaus Graz II Standort West

Graz, , Austria

Site Status

Medical University of Graz

Graz, , Austria

Site Status

Uniklinikum Salzburg

Salzburg, , Austria

Site Status

Krankenanstalt Rudolfstiftung

Vienna, , Austria

Site Status

Allgemeines Krankenhaus Vienna

Vienna, , Austria

Site Status

Countries

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Austria

References

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Tripolt NJ, Kolesnik E, Pferschy PN, Verheyen N, Ablasser K, Sailer S, Alber H, Berger R, Kaulfersch C, Leitner K, Lichtenauer M, Mader A, Moertl D, Oulhaj A, Reiter C, Rieder T, Saely CH, Siller-Matula J, Weidinger F, Zechner PM, von Lewinski D, Sourij H; EMMY study group. Impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction-The EMMY trial. Am Heart J. 2020 Mar;221:39-47. doi: 10.1016/j.ahj.2019.12.004. Epub 2019 Dec 12.

Reference Type BACKGROUND
PMID: 31901799 (View on PubMed)

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.

Reference Type RESULT
PMID: 36036746 (View on PubMed)

Benedikt M, Mangge H, Aziz F, Curcic P, Pailer S, Herrmann M, Kolesnik E, Tripolt NJ, Pferschy PN, Wallner M, Zirlik A, Sourij H, von Lewinski D. Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction - a post-hoc analysis of the EMMY trial. Cardiovasc Diabetol. 2023 Jul 5;22(1):166. doi: 10.1186/s12933-023-01904-6.

Reference Type RESULT
PMID: 37407956 (View on PubMed)

Aziz F, Tripolt NJ, Pferschy PN, Kolesnik E, Mangge H, Curcic P, Hermann M, Meinitzer A, von Lewinski D, Sourij H; EMMY Investigators. Alterations in trimethylamine-N-oxide in response to Empagliflozin therapy: a secondary analysis of the EMMY trial. Cardiovasc Diabetol. 2023 Jul 20;22(1):184. doi: 10.1186/s12933-023-01920-6.

Reference Type RESULT
PMID: 37475009 (View on PubMed)

von Lewinski D, Kolesnik E, Aziz F, Benedikt M, Tripolt NJ, Wallner M, Pferschy PN, von Lewinski F, Schwegel N, Holman RR, Oulhaj A, Moertl D, Siller-Matula J, Sourij H. Timing of SGLT2i initiation after acute myocardial infarction. Cardiovasc Diabetol. 2023 Sep 30;22(1):269. doi: 10.1186/s12933-023-02000-5.

Reference Type RESULT
PMID: 37777743 (View on PubMed)

Sourij C, Oulhaj A, Aziz F, Tripolt NJ, Aberer F, Pferschy PN, Postula M, Drexel H, Benedikt M, Kolesnik E, Pieber TR, Bugger H, von Lewinski D, Sourij H. Impact of glycaemic status on the cardiac effects of empagliflozin when initiated immediately after myocardial infarction: A post-hoc analysis of the EMMY trial. Diabetes Obes Metab. 2024 May;26(5):1971-1975. doi: 10.1111/dom.15477. Epub 2024 Jan 29. No abstract available.

Reference Type RESULT
PMID: 38287198 (View on PubMed)

Sourij C, Aziz F, Tripolt NJ, Siller-Matula J, Pferschy PN, Kolesnik E, Wallner M, Eyileten C, Postula M, Oulhaj A, Sourij H, von Lewinski D; EMMY study group. Effects of empagliflozin in women and men with acute myocardial infarction: An analysis from the EMMY trial. Hellenic J Cardiol. 2024 Jan-Feb;75:3-8. doi: 10.1016/j.hjc.2023.05.007. Epub 2023 May 24.

Reference Type RESULT
PMID: 37236318 (View on PubMed)

Schwegel N, Strohhofer C, Kolesnik E, Oltean S, Huttmair A, Pipp C, Benedikt M, Verheyen N, Gollmer J, Ablasser K, Wallner M, Santner V, Tripolt N, Pferschy P, Zechner P, Alber H, Siller-Matula JM, Kopp K, Zirlik A, Aziz F, Sourij H, von Lewinski D. Impact of empagliflozin on cardiac structure and function assessed by echocardiography after myocardial infarction: a post-hoc sub-analysis of the emmy trial. Clin Res Cardiol. 2025 May;114(5):629-639. doi: 10.1007/s00392-024-02523-1. Epub 2024 Sep 16.

Reference Type DERIVED
PMID: 39297940 (View on PubMed)

Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.

Reference Type DERIVED
PMID: 34693515 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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HS-2017-01

Identifier Type: -

Identifier Source: org_study_id

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