EMPACT-MI: A Study to Test Whether Empagliflozin Can Lower the Risk of Heart Failure and Death in People Who Had a Heart Attack (Myocardial Infarction)

Study Overview
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Brief Summary
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This is a study in adults who had a heart attack (myocardial infarction). The purpose of this study is to find out whether a medicine called empagliflozin helps to lower the chances of having to go to the hospital for heart failure and whether it lowers the chances of dying from cardiovascular disease. People who are in hospital may join the study soon after being treated for their heart attack. Participants are put into 2 groups by chance. One group takes 1 empagliflozin tablet a day. The other group takes 1 placebo tablet a day. Placebo tablets look like empagliflozin tablets but do not contain any medicine. All participants continue their standard treatment. Empagliflozin belongs to a class of medicines known as SGLT-2 inhibitors. Empagliflozin is a medicine that helps people with type 2 diabetes to lower their blood sugar. Researchers think that empagliflozin might also help people after heart attack who are at risk for heart failure, whether or not they have diabetes. Participants are in the study for about 1 to 2 years. During this time, there are about 4 visits inperson, 2 visits are done either by phone or by use of an mobile application. Results between the empagliflozin and placebo groups are compared. The doctors also regularly check the general health of the participants.

Official Title
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EMPACT-MI: A Streamlined, Multicentre, Randomised, Parallel Group, Double-blind Placebo-controlled Superiority Trial to Evaluate the Effect of EMPAgliflozin on Hospitalisation for Heart Failure and Mortality in Patients With aCuTe Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Of full age of consent (according to local legislation, at least ≥ 18 years) at screening. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. Diagnosis of spontaneous Acute Myocardial Infarction (AMI): ST-Elevation Myocardial Infarction (STEMI) or Non-ST Elevation Myocardial Infarction (NSTEMI) with randomisation to occur no later than 14 calendar days after hospital admission. For patients with an in-hospital Myocardial Infarction (MI) as qualifying event, randomization must still occur within 14 days of hospital admission. High risk of HF, defined as EITHER Symptoms (e.g. dyspnea; decreased exercise tolerance; fatigue), or signs of congestion (e.g. pulmonary rales, crackles or crepitations; elevated jugular venous pressure; congestion on chest X-ray), that require treatment (e.g. augmentation or initiation of oral diuretic therapy; i.v. diuretic therapy; i.v. vasoactive agent; mechanical intervention etc.) at any time during the hospitalization. OR Newly developed Left Ventricular Ejection Fraction (LVEF) < 45% as measured by echocardiography, ventriculography, cardiac Computer Tomography (CT), Magnetic Resonance Imaging (MRI) or radionuclide imaging during index hospitalisation. In addition at least one of the following risk factors: Age > 65 years, Newly developed LVEF < 35%, Prior MI (before index MI) documented in medical records, Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 (using Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI) formula based on creatinine from local lab at any time during index hospitalisation), Atrial fibrillation (persistent or permanent ; if paroxysmal, only valid if associated with index MI), Type 2 diabetes mellitus (prior or new diagnosis), N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) >1,400 pg/mL for patients in sinus rhythm, >2,800 pg/mL if atrial fibrillation; Brain Natriuretic Peptide (BNP) >350 pg/mL for patients in sinus rhythm, >700 pg/mL if atrial fibrillation, measured at any time during hospitalisation, Uric acid >7.5 mg/dL (>446 μmol/L), measured at any time during hospitalisation, Pulmonary Artery Systolic Pressure [or right ventricular systolic pressure] >40 mmHg (non-invasive [usually obtained from clinically indicated post-MI echocardiography] or invasive, at any time during hospitalisation), Patient not revascularized (and no planned revascularization) for the index MI (Includes e.g. patients where no angiography is performed, unsuccessful revascularization attempts, diffuse atherosclerosis not amenable for intervention; but does NOT include if revascularization was not performed due to nonobstructive coronary arteries), 3-vessel coronary artery disease at time of index MI, Diagnosis of peripheral artery disease (extracoronary vascular disease, e.g. lower extremity artery disease or carotid artery disease). Exclusion Criteria: Diagnosis of chronic Heart Failure (HF) prior to index MI. Systolic blood pressure < 90 mmHg at randomisation. Cardiogenic shock or use of i.v. inotropes in last 24 hours before randomisation. Coronary Artery Bypass Grafting planned at time of randomisation. Current diagnosis of Takotsubo cardiomyopathy. Any current severe (stenotic or regurgitant) valvular heart disease. eGFR < 20 ml/min/1.73m2 (using CKD-EPI formula based on most recent creatinine from local lab during index hospitalisation) or on dialysis. Type I diabetes mellitus. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empagliflozin<br> | Drug: Empagliflozin<br>* Empagliflozin<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of time to first heart failure hospitalisation or all-cause mortality |  | up to 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of HHF or all-cause mortality |  | up to 26 months | 
| Total number of non-elective Cardiovascular (CV) hospitalisations or all-cause mortality |  | up to 26 months | 
| Total number of non-elective all-cause hospitalisations or all-cause mortality |  | up to 26 months | 
| Total number of hospitalisations for MI or all-cause mortality |  | up to 26 months | 
| Time to CV mortality |  | up to 26 months |