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)

• ClinicalTrials.gov Identifier: NCT04509674
• Recruitment Status: Recruiting
• First Posted: August 12, 2020
• Last Update Posted: March 7, 2023
• Sponsor: Boehringer Ingelheim
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: August 10, 2020
• First Posted Date: August 12, 2020
• Last Update Posted Date: March 7, 2023
• Actual Study Start Date: December 16, 2020
• Estimated Primary Completion Date: August 31, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 31, 2022): Composite of time to first heart failure hospitalisation or all-cause mortality [ Time Frame: up to 26 months ]
• Original Primary Outcome Measures (submitted: August 10, 2020): Composite of time to first heart failure hospitalisation or all-cause mortality [ Time Frame: up to 24 months ]

Current Secondary Outcome Measures (submitted: May 31, 2022)

• Total number of HHF or all-cause mortality [ Time Frame: up to 26 months ]
• Total number of non-elective Cardiovascular (CV) hospitalisations or all-cause mortality [ Time Frame: up to 26 months ]
• Total number of non-elective all-cause hospitalisations or all-cause mortality [ Time Frame: up to 26 months ]
• Total number of hospitalisations for MI or all-cause mortality [ Time Frame: up to 26 months ]
• Time to CV mortality [ Time Frame: up to 26 months ]

Original Secondary Outcome Measures (submitted: August 10, 2020)

• Total number of HHF or all-cause mortality [ Time Frame: up to 24 months ]
• Total number of non-elective Cardiovascular (CV) hospitalisations or all-cause mortality [ Time Frame: up to 24 months ]
• Total number of non-elective all-cause hospitalisations or all-cause mortality [ Time Frame: up to 24 months ]
• Total number of hospitalisations for MI or all-cause mortality [ Time Frame: up to 24 months ]
• Time to CV mortality [ Time Frame: up to 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Blinded investigator review of events in place of centralized adjudication.

Primary Purpose: Treatment

• Condition: Myocardial Infarction

Intervention

• Drug: Empagliflozin
  Empagliflozin
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Empagliflozin
  Intervention: Drug: Empagliflozin
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 17, 2022): 6500
• Original Estimated Enrollment (submitted: August 10, 2020): 3312
• Estimated Study Completion Date: August 31, 2023
• Estimated Primary Completion Date: August 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Of full age of consent (according to local legislation, at least ≥ 18 years) at screening.
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
3. 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.
4. 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.

5. High risk of HF, defined as EITHER

   1. 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

   2. 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.

6. 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:

1. Diagnosis of chronic Heart Failure (HF) prior to index MI.
2. Systolic blood pressure < 90 mmHg at randomisation.
3. Cardiogenic shock or use of i.v. inotropes in last 24 hours before randomisation.
4. Coronary Artery Bypass Grafting planned at time of randomisation.
5. Current diagnosis of Takotsubo cardiomyopathy.
6. Any current severe (stenotic or regurgitant) valvular heart disease.
7. eGFR < 20 ml/min/1.73m2 (using CKD-EPI formula based on most recent creatinine from local lab during index hospitalisation) or on dialysis.
8. Type I diabetes mellitus. Further exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Boehringer Ingelheim; 1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

Contact: Duke Clinical Research Institute; +1 919 668-8300; EMPACT-MI@dm.duke.edu

• Listed Location Countries: Argentina, Australia, Brazil, Bulgaria, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine, United States

Administrative Information

• NCT Number: NCT04509674
• Other Study ID Numbers: 1245-0202; 2019-001037-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Eli Lilly and Company
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: March 2023