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EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction (EMPRESS MI)

Primary Purpose

Myocardial Infarction

Status
Not yet recruiting
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Placebo
Sponsored by
NHS Greater Glasgow and Clyde
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Infarction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • • Male or female ≥18 years of age

    • Informed consent
    • Diagnosis of a type 1 acute myocardial infarction meeting the Fourth Universal Definition of Myocardial Infarction (STEMI or NSTEMI)
    • Left ventricular ejection fraction ≤40% as measured by cardiac MRI performed ≥12 hours and ≤14 days following hospital admission with an acute type 1 myocardial infarction). For patients with an in-hospital myocardial infarction as qualifying event, randomization must still occur within 14 days of hospital admission.
    • eGFR ≥30 ml/min/1.73m2 at the time of randomisation (calculated using the CKD-EPI formula)

Exclusion Criteria:

  • Inability to give informed consent e.g. due to significant cognitive impairment.

    • Diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) prior to admission with acute myocardial infarction.
    • 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 (CABG) planned at time of randomisation.
    • Type II acute myocardial infarction
    • Any current severe (stenotic) valvular heart disease.
    • Diagnosis of Takotsubo cardiomyopathy
    • Type I diabetes mellitus.
    • History of ketoacidosis.
    • Pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device.
    • Permanent or persistent atrial fibrillation.
    • Enrollment in another randomised clinical trial involving medical or device-based interventions (co-enrolment in observational studies is permitted)
    • Currently pregnant, planning pregnancy, or currently breastfeeding
    • History of allergy to SGLT2i.
    • Current or planned use of an SGLT2i at time of randomisation.
    • Active genital tract infections.
    • Anyone who, in the investigators' opinion, is not suitable to participate in the trial for other reasons.
    • Contra-indication to contrast-enhanced cardiac MRI i.e. claustrophobia, metallic foreign object unsuitable for MRI

Sites / Locations

  • Glasgow Royal Infirmary
  • Golden Jubilee National Hospital
  • NHS Greater Glasgow and Clyde

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

empagliflozin

Placebo

Arm Description

empagliflozin 10mg once daily

matched placebo

Outcomes

Primary Outcome Measures

left ventricular end-systolic volume indexed to body surface area (LVESVI)
change in left ventricular volume measured by cardiac MR measured in ml/m2

Secondary Outcome Measures

Change in left ventricular end diastolic volume indexed to body surface area (LVEDVI)
Change in left ventricular end diastolic volume indexed to body surface area (LVEDVI) measured by cardiac MR in ml/m2
Change in left ventricular ejection fraction (LVEF)
Change in left ventricular ejection fraction (LVEF) measured by cardian MR in percentage
Change in left atrial volume indexed to body surface area (LAVI)
Change in left atrial volume indexed to body surface area (LAVI) measured by cardiac MR in ml/m2
Change in left ventricular mass indexed to body surface area (LVMI)
Change in left ventricular mass indexed to body surface area (LVMI) measured by cardiac MR in grams/m2
Change in N-terminal pro-B-type natriuretic peptide
Change in N-terminal pro-B-type natriuretic peptide measured in pg/ml
Change in high-sensitivity troponin I
Change in high-sensitivity troponin I in ng/ml
Change in infarct size
Change in infarct size measured by cardiac MR in cm2

Full Information

First Posted
August 19, 2021
Last Updated
August 25, 2021
Sponsor
NHS Greater Glasgow and Clyde
Collaborators
University of Glasgow
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1. Study Identification

Unique Protocol Identification Number
NCT05020704
Brief Title
EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction
Acronym
EMPRESS MI
Official Title
EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2021 (Anticipated)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
April 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NHS Greater Glasgow and Clyde
Collaborators
University of Glasgow

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The addition of the SGLT2 inhibitor empagliflozin 10mg once daily to standard-of-care therapy administered early following acute myocardial infarction will result in a greater attenuation of adverse left ventricular remodelling, compared with matched placebo, in patients with left ventricular systolic dysfunction as a result of an acute myocardial infarction.
Detailed Description
To date, the administration of an SGLT2i has not been proven to improve outcomes when commenced in patients immediately after acute myocardial infarction. In the EMPA-REG OUTCOME trial, which only studied patients with type 2 diabetes, patients were excluded from enrolment if they had had a myocardial infarction in the two months prior to randomisation. Similarly, in the EMPEROR-Reduced trial, patients who had had a myocardial infarction within the previous 90 days were excluded. Two trials are currently examining the effect of the addition of an SGLT2i to standard therapy on outcomes in patients following myocardial infarction; DAPA-MI (ClinicalTrials.gov unique identifier NCT04564742) and EMPACT-MI (NCT04509674). Given the observed benefits in patients with and without diabetes in EMPEROR-Reduced and DAPA-HF, the investigators will recruit all patients irrespective of diabetes status in the present trial. The dose (10mg once daily) of empagliflozin is based on the dose used in licensed indications and the clinical benefit and safety results seen with this dose in EMPEROR-Reduced and EMPA-REG OUTCOME.21 Cardiac MRI is the reference method of assessment of LV mass, volumes and ejection fraction. It has the additional benefit of allowing assessment of myocardial viability, tissue characterisation, myocardial fibrosis and regional dysfunction.31 LVESVI has been shown to be a major determinant of survival after myocardial infarction.32,33 The degree of LV remodelling and effect of treatment will be measured by the primary endpoint of the change in LVESVI from baseline to 24 +/- 4 weeks Microvascular obstruction within the infarct core is independently associated with an adverse prognosis, and the magnitude of this association is greater than for infarct size. The investigators research in the British Heart Foundation MR-MI study (NCT02072850) highlighted the complex nature of microvascular obstruction in post-MI patients and, to date, there are no evidence-based treatments for this problem. Microvascular obstruction and, relatedly, myocardial haermorrhage, are associated with adverse left ventricular remodelling, and, potentially, these infarct core microvascular pathologies represent a therapeutic target for limiting adverse left ventricular remodelling. Myocardial inflammation is a characteristic feature of acute myocardial infarction. However, dysregulation of myocardial inflammation, particularly in ventricular tissue that is remote from the infarct zone, may lead to enhanced tissue fibrosis and adverse left ventricular remodelling. In the BHF MR-MI study, we found that an imaging biomarker of inflammation (T1) was independently predictive of adverse left ventricular remodelling at 6 months post-MI. The investogators also found that extracellular volume fraction (ECV) was also associated with adverse remodelling. Renal dysfunction early post-MI is an adverse prognostic marker. SGLT2i have favourable effects on renal function in patients with chronic kidney disease with and without type 2 diabetes mellitus and/or HFrEF. The effects of SGLT2i on renal function in post-MI patients are uncertain. The investigators will therefore assess the effects of SGLT2i with empagliflozin on renal function (estimated glomerular filtration rate, urine creatinine: albumin ratio) and renal tissue characteristics revealed by MRI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
empagliflozin
Arm Type
Experimental
Arm Description
empagliflozin 10mg once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
matched placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Intervention Description
SGLT2inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Primary Outcome Measure Information:
Title
left ventricular end-systolic volume indexed to body surface area (LVESVI)
Description
change in left ventricular volume measured by cardiac MR measured in ml/m2
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in left ventricular end diastolic volume indexed to body surface area (LVEDVI)
Description
Change in left ventricular end diastolic volume indexed to body surface area (LVEDVI) measured by cardiac MR in ml/m2
Time Frame
24 weeks
Title
Change in left ventricular ejection fraction (LVEF)
Description
Change in left ventricular ejection fraction (LVEF) measured by cardian MR in percentage
Time Frame
24 weeks
Title
Change in left atrial volume indexed to body surface area (LAVI)
Description
Change in left atrial volume indexed to body surface area (LAVI) measured by cardiac MR in ml/m2
Time Frame
24 weeks
Title
Change in left ventricular mass indexed to body surface area (LVMI)
Description
Change in left ventricular mass indexed to body surface area (LVMI) measured by cardiac MR in grams/m2
Time Frame
24 weeks
Title
Change in N-terminal pro-B-type natriuretic peptide
Description
Change in N-terminal pro-B-type natriuretic peptide measured in pg/ml
Time Frame
24 weeks
Title
Change in high-sensitivity troponin I
Description
Change in high-sensitivity troponin I in ng/ml
Time Frame
24 weeks
Title
Change in infarct size
Description
Change in infarct size measured by cardiac MR in cm2
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: • Male or female ≥18 years of age Informed consent Diagnosis of a type 1 acute myocardial infarction meeting the Fourth Universal Definition of Myocardial Infarction (STEMI or NSTEMI) Left ventricular ejection fraction ≤40% as measured by cardiac MRI performed ≥12 hours and ≤14 days following hospital admission with an acute type 1 myocardial infarction). For patients with an in-hospital myocardial infarction as qualifying event, randomization must still occur within 14 days of hospital admission. eGFR ≥30 ml/min/1.73m2 at the time of randomisation (calculated using the CKD-EPI formula) Exclusion Criteria: Inability to give informed consent e.g. due to significant cognitive impairment. Diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) prior to admission with acute myocardial infarction. 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 (CABG) planned at time of randomisation. Type II acute myocardial infarction Any current severe (stenotic) valvular heart disease. Diagnosis of Takotsubo cardiomyopathy Type I diabetes mellitus. History of ketoacidosis. Pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device. Permanent or persistent atrial fibrillation. Enrollment in another randomised clinical trial involving medical or device-based interventions (co-enrolment in observational studies is permitted) Currently pregnant, planning pregnancy, or currently breastfeeding History of allergy to SGLT2i. Current or planned use of an SGLT2i at time of randomisation. Active genital tract infections. Anyone who, in the investigators' opinion, is not suitable to participate in the trial for other reasons. Contra-indication to contrast-enhanced cardiac MRI i.e. claustrophobia, metallic foreign object unsuitable for MRI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kieran F Docherty, MBChB
Phone
0131 330 2467
Email
kieran.docherty@glasgow.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Jaclyn Carberry, MBChB
Phone
0141 330 2467
Email
jaclyn.carberry@glasgow.ac.uk
Facility Information:
Facility Name
Glasgow Royal Infirmary
City
Glasgow
State/Province
Strathclyde
ZIP/Postal Code
G4 0SF
Country
United Kingdom
Facility Name
Golden Jubilee National Hospital
City
Glasgow
ZIP/Postal Code
G81 4HX
Country
United Kingdom
Facility Name
NHS Greater Glasgow and Clyde
City
Glasgow
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
To be discussed

Learn more about this trial

EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction

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