Myocardial InfarctionPhase 3EMPRESS-MINCT05020704
EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction
A Phase 3 study testing Empagliflozin 10 MG in people with Myocardial Infarction, run by NHS Greater Glasgow and Clyde at 3 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- Empagliflozin 10 MG
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 16 Sep 2022to 12 Jun 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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 <45% (changed from ≤40% by an amendment to the trial protocol on 23/Feb/2023) 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)
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Glasgow Royal Infirmary
Glasgow, Strathclyde, G4 0SF
Golden Jubilee National Hospital
Glasgow, G81 4HX
NHS Greater Glasgow and Clyde
Glasgow
About this study
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.
Read the 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.
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. LVESVI has been shown to be a major determinant of survival after myocardial infarction. 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 haemorrhage, 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 investigators 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.
- Conditions
- Myocardial Infarction
- Being tested
- Empagliflozin 10 MG, Placebo
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
SGLT2inhibitor
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| empagliflozin | Experimental | empagliflozin 10mg once daily Receives: Drug: Empagliflozin 10 MG |
| Placebo | Placebo comparator | matched placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular end-systolic volume indexed to body surface area (LVESVI)
Change in left ventricular end-systolic volume measured by cardiac MR measured in ml/m2
Measured: 24 weeks
Secondary outcomes (7)
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
Measured: 24 weeks
Change in left ventricular ejection fraction (LVEF)
Change in left ventricular ejection fraction (LVEF) measured by cardian MR in percentage
Measured: 24 weeks
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
Measured: 24 weeks
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
Measured: 24 weeks
Change in N-terminal pro-B-type natriuretic peptide
Change in N-terminal pro-B-type natriuretic peptide measured in pg/ml
Measured: 24 weeks
Change in high-sensitivity troponin I
Change in high-sensitivity troponin I in ng/ml
Measured: 24 weeks
Change in infarct size
Change in infarct size measured by cardiac MR in cm2
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start16 Sep 2022
- Primary completion12 Jun 2024 (estimated)
- Study completion12 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05020704
- Sponsor's protocol ID
- GN21CA051
- Acronym
- EMPRESS-MI
- Status last verified
- Apr 2024
- First submitted
- 19 Aug 2021
- Last updated
- 2 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: To be discussed
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction
- ClinicalTrials.gov ID
- NCT05020704
- Acronym / sponsor ID
- EMPRESS-MI / GN21CA051
- Conditions
- Myocardial Infarction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow
- Study start
- 16 Sep 2022 (actual)
- Primary completion
- 12 Jun 2024 (estimated)
- Study completion
- 12 Jun 2024 (estimated)
- First posted
- 25 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. LVESVI has been shown to be a major determinant of survival after myocardial infarction. 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 haemorrhage, 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 investigators 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| empagliflozin | Experimental | Drug: Empagliflozin 10 MGempagliflozin 10mg once daily |
| Placebo | Placebo comparator | Drug: Placebomatched placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- • Male or female ≥18 years of age
Key exclusion criteria (19 listed)
- Inability to give informed consent e.g. due to significant cognitive impairment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 10 MGSGLT2inhibitor | Drug | empagliflozin |
| PlaceboMatched placebo | Drug | Placebo |
Primary outcome
Left ventricular end-systolic volume indexed to body surface area (LVESVI)
Time frame: 24 weeks
Change in left ventricular end-systolic volume measured by cardiac MR measured in ml/m2
7 secondary outcomes
Change in left ventricular end-diastolic volume indexed to body surface area (LVEDVI)
Time frame: 24 weeks
Change in left ventricular ejection fraction (LVEF)
Time frame: 24 weeks
Change in left atrial volume indexed to body surface area (LAVI)
Time frame: 24 weeks
Change in left ventricular mass indexed to body surface area (LVMI)
Time frame: 24 weeks
Change in N-terminal pro-B-type natriuretic peptide
Time frame: 24 weeks
Change in high-sensitivity troponin I
Time frame: 24 weeks
Change in infarct size
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Individual participant dataSharing planned: Undecided. To be discussed
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Empagliflozin 10 MG in people with Myocardial Infarction, run by NHS Greater Glasgow and Clyde at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular end-systolic volume indexed to body surface area (LVESVI) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.