Peri-treatment of SGLT-2 Inhibitor on Myocardial Infarct Size and Remodeling Index in Patients With Acute Myocardial Infarction and High Risk of Heart Failure Undergoing Percutaneous Coronary Intervention

Heart Failure Clinical Trial

— PRESTIGE-AMI  

Official title:

Peri-tREatment of SGLT-2 Inhibitor on Myocardial Infarct Size and Remodeling Index Measured by Cardiac maGnetic rEsonance Imaging in Patients With Acute Myocardial Infarction and High Risk of Heart Failure Undergoing Percutaneous Coronary Intervention

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04899479
• Other study ID #: PRESTIGE-AMI
• Status: Recruiting
• Phase: Phase 4
• Start date: July 5, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2023
• Source: Samsung Medical Center
• Contact: Young Bin Song, MD, PhD
• Phone: 82-2-3410-1246
• Email: youngbin.song[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We aimed to identify whether SGLT-2 inhibitor administration before and after coronary intervention is effective in reducing the size of infarction and myocardial remodeling in patients with acute myocardial infarction (AMI) and high risk of heart failure, and its mechanism. For this reason, we compared cardiac magnetic resonance imaging (CMR) parameters and clinical outcomes between the SGLT-2 inhibitor group and the control group to confirm the efficacy and safety of SGLT-2 inhibitors.

Description:

After the introduction of percutaneous coronary intervention (PCI) as a method to normalize blood flow in the treatment of coronary artery disease, not only the technical aspects of coronary intervention but also the devices and medications have been improved over the past 30 years. However, despite these advances, morbidity, and mortality of AMI are still high. In particular, in patients with ST-segment elevation MI (STEMI), the 1-year mortality rate and hospitalization rate due to heart failure are 10%, and 22%, respectively. Accordingly, various efforts are being made to improve the prognosis of AMI and to reduce the infarct size, which is a major prognostic factor. The most effective method for achieving this goal to early and successful revascularization by PCI. However, restoring blood flow, which is a prerequisite for relieving ischemia, can paradoxically cause damage to the myocardium and death of the myocardium by itself. This phenomenon is called myocardial reperfusion injury. Several pharmacological and mechanical treatments targeting this phenomenon have been studied, and the experimental and small-scale clinical trials have been shown to have the effect of reducing infarct size and relieving myocardium.4 However, to date, large-scale clinical trials have not demonstrated clinical benefits.

SGLT-2 inhibitors are developed to lower blood sugar and treat type 2 diabetes mellitus (DM) by inhibiting Sodium glucose co-transporter-2 in proximal renal tubule, releasing glucose into the urine and preventing reabsorption. However, SGLT-2 inhibitors are known to have an effect on lowering cardiovascular events in addition to lowering blood sugar. In three large-scale, multicenter, randomized trials to evaluate the effects of SGLT-2 in type 2 diabetic patients, the combined outcome consisting of cardiac death or readmission due to heart failure was significantly lowered compared to the placebo group. In particular, DECLARE-TIMI 58 trial confirmed that this effect was consistent regardless of the history of atherosclerotic cardiovascular disease or heart failure.8 In addition, DAPA-CKD trial showed that SGLT-2 inhibitor significantly reduced the composite outcome consisting of cardiovascular death or readmission due to heart failure as well as the kidney-related outcome compared to the placebo group in patients with chronic kidney disease regardless of type 2 DM. Similarly, EMPEROR-Reduced and DAPA-HF trials consistently demonstrated that SGLT-2 inhibitor was associated with significantly lower risk of a composite of cardiovascular death or worsening heart failure in patients with heart failure with reduced ejection fraction. Therefore, the current guideline recommended the use of SGLT-2 inhibitor in patients with heart failure with reduced ejection fraction, with a conjunction of goal-directed medical therapy. Nevertheless, the mechanism that can explain this has been extensively investigated, but it is not clear yet. Several potential hypotheses have been proposed as mechanisms such as increased natriuresis, decreased blood pressure, decreased inflammation, and decreased reactive oxidative stress. In this regard, it is anticipated that the use of SGLT-2 inhibitors will benefit even in patients with AMI and high risk of heart failure in both acute and chronic phases.

Therefore, we aimed to identify whether SGLT-2 inhibitor administration before and after coronary intervention is effective in reducing the size of infarction and myocardial remodeling in patients with AMI and high risk of heart failure, and its mechanism. For this reason, we compared CMR parameters and clinical outcomes between the SGLT-2 inhibitor group and the control group to confirm the efficacy and safety of SGLT-2 inhibitors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1) Subject must be at least 18 years of age 2) Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving SGLT-2 inhibitor and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure 3) Diagnosis of Type 1 myocardial infarction (MI) (ST-segment elevation MI [STEMI] or Non-ST-segment elevation MI [NSTEMI]) i) Detection of a rise and/or fall of cardiac troponin values with at least 1 value above the 99th percentile upper reference limit ii) Symptoms or electrocardiographic changes suggesting myocardial ischemia 4) High risk of heart failure (at least one of the two criteria below are met) i) Left ventricular ejection fraction < 50% ii) Symptoms or signs of pulmonary congestion requiring treatment

Exclusion Criteria:

• 1) Target lesion is not suitable for PCI by operator's decision 2) Patients requiring cardiopulmonary resuscitation due to cardiac arrest before randomization 3) Rescue PCI after thrombolysis or facilitated PCI 4) Previous MI 5) Previous history of heart failure 6) Patients who have been taking SGLT-2 inhibitor 7) Patients with glomerular filtration rate < 30ml/min/1.73m2 or on dialysis 8) Type 1 diabetes mellitus (DM) 9) Known hypersensitivity or contraindications to study medications (SGLT-2 inhibitor) 10) Pregnant or lactating women 11) Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment)

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Heart Failure
• Infarction
• Myocardial Infarction

Intervention

Drug:
• SGLT2 inhibitor
In patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.

Other:
• Control
In patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial infract size (IS)	IS measured using CMR	at 6-month follow-up
Primary	?Left ventricular end-systolic volume	Difference of left ventricular end-systolic volume measured by CMR	Between index hospitalization and 6-month follow-up
Secondary	Acute kidney injury	According to KDIGO guideline	Within 3 days after index PCI
Secondary	Myocardial IS	IS measured using CMR	Within 3 days after index PCI
Secondary	Myocardial salvage index (MSI)	MSI measured using CMR	Within 3 days after index PCI
Secondary	Microvascular obstruction (MVO)	MVO measured using CMR	Within 3 days after index PCI
Secondary	Hemorraghic infarction (HI)	HI measured using CMR	Within 3 days after index PCI
Secondary	IS	measured by peak cardiac enzyme	Within 3 days after index PCI
Secondary	Thrombolysis in myocardial infarction (TIMI) flow grade	TIMI flow grade after successful PCI	Immediate after index PCI
Secondary	ST resolution after PCI	ST segment change after PCI	Immediate after index PCI
Secondary	?left ventricular end-diastolic volume	Difference of left ventricular end-diastolic volume measured using CMR	Between index hospitalization and 6-month follow-up
Secondary	?left ventricular ejection fraction	Difference of left ventricular ejection fraction measured using CMR	Between index hospitalization and 6-month follow-up
Secondary	LV adverse remodeling	measured by CMR	Between index hospitalization and 6-month follow-up
Secondary	LV reverse remodeling	measured by CMR	Between index hospitalization and 6-month follow-up
Secondary	MSI	measured using CMR	at 6-month follow-up
Secondary	MVO	measured using CMR	at 6-month follow-up
Secondary	HI	measured using CMR	at 6-month follow-up
Secondary	Changes of NT-proBNP level	Difference of NT-proBNP	Between index hospitalization and 6-month follow-up
Secondary	Estimated glomerular filtration rate	Kidney function	6 months after index PCI
Secondary	Cardiac death or re-hospitalization due to heart failure	a composite of cardiac death or re-hospitalization due to heart failure	6 months after index PCI
Secondary	All-cause death or re-hospitalization due to heart failure	a composite of all-cause death or re-hospitalization due to heart failure	6 months after index PCI
Secondary	Target lesion failure	a composite of cardiac death, MI, or clinically indicated target-lesion revascularization	6 months after index PCI
Secondary	Target vessel failure	a composite of cardiac death, MI, or clinically indicated target-vessel revascularization	6 months after index PCI
Secondary	All-cause death	All-cause death during follow-up	6 months after index PCI
Secondary	Cardiac death	Cardiac death during follow-up	6 months after index PCI
Secondary	Target vessel MI	Target vessel MI during follow-up	6 months after index PCI
Secondary	Target lesion revascularization	Target lesion revascularization during follow-up	6 months after index PCI
Secondary	Re-hospitalization due to heart failure	Re-hospitalization due to heart failure during follow-up	6 months after index PCI
Secondary	Any re-hospitalization	Any re-hospitalization during follow-up	6 months after index PCI