Ignite Creation Date:
2025-12-24 @ 9:19 PM
Ignite Modification Date:
2025-12-25 @ 7:06 PM
Study NCT ID:
NCT05020704
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-04-02
First Post:
2021-08-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction
Sponsor:
NHS Greater Glasgow and Clyde
Organization:
Study Overview
Official Title:
EMpagliflozin to PREvent worSening of Left Ventricular Volumes and Systolic Function After Myocardial Infarction
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EMPRESS-MI
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.
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: