Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pre, Post-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 (PRESTIGE-AMI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04899479
Recruitment Status : Not yet recruiting
First Posted : May 24, 2021
Last Update Posted : May 28, 2021
Sponsor:
Information provided by (Responsible Party):
Young Bin Song, Samsung Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Heart Failure Drug: SGLT2 inhibitor Other: Control Phase 4

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomization will be performed 1:1 between SGLT-2 inhibitor and control. Stratification will be done by DM and clinical presentation (STEMI vs. NSTEMI).
Masking: None (Open Label)
Masking Description: This is an open-label study, therefore, no masking will be performed.
Primary Purpose: Treatment
Official Title: PRE, Post-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
Estimated Study Start Date : June 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SGLT-2 inhibitor
The SGLT-2 inhibitor group will receive SGLT-2 inhibitor once daily until the end of the study period.
Drug: SGLT2 inhibitor
After successful PCI in patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.

Placebo Comparator: Control
The control group will not receive any additional drugs.
Other: Control
After successful PCI in patients with AMI and high risk of heart failure, 1:1 randomization will be performed to either SGLT2 inhibitor or control group.




Primary Outcome Measures :
  1. Myocardial infract size (IS) [ Time Frame: at 6-month follow-up ]
    IS measured using CMR

  2. ∆Left ventricular end-systolic volume [ Time Frame: Between index hospitalization and 6-month follow-up ]
    Difference of left ventricular end-systolic volume measured by CMR


Secondary Outcome Measures :
  1. Acute kidney injury [ Time Frame: Within 3 days after index PCI ]
    According to KDIGO guideline

  2. Myocardial IS [ Time Frame: Within 3 days after index PCI ]
    IS measured using CMR

  3. Myocardial salvage index (MSI) [ Time Frame: Within 3 days after index PCI ]
    MSI measured using CMR

  4. Microvascular obstruction (MVO) [ Time Frame: Within 3 days after index PCI ]
    MVO measured using CMR

  5. Hemorraghic infarction (HI) [ Time Frame: Within 3 days after index PCI ]
    HI measured using CMR

  6. IS [ Time Frame: Within 3 days after index PCI ]
    measured by peak cardiac enzyme

  7. Thrombolysis in myocardial infarction (TIMI) flow grade [ Time Frame: Immediate after index PCI ]
    TIMI flow grade after successful PCI

  8. ST resolution after PCI [ Time Frame: Immediate after index PCI ]
    ST segment change after PCI

  9. ∆left ventricular end-diastolic volume [ Time Frame: Between index hospitalization and 6-month follow-up ]
    Difference of left ventricular end-diastolic volume measured using CMR

  10. ∆left ventricular ejection fraction [ Time Frame: Between index hospitalization and 6-month follow-up ]
    Difference of left ventricular ejection fraction measured using CMR

  11. LV adverse remodeling [ Time Frame: Between index hospitalization and 6-month follow-up ]
    measured by CMR

  12. LV reverse remodeling [ Time Frame: Between index hospitalization and 6-month follow-up ]
    measured by CMR

  13. MSI [ Time Frame: at 6-month follow-up ]
    measured using CMR

  14. MVO [ Time Frame: at 6-month follow-up ]
    measured using CMR

  15. HI [ Time Frame: at 6-month follow-up ]
    measured using CMR

  16. Changes of NT-proBNP level [ Time Frame: Between index hospitalization and 6-month follow-up ]
    Difference of NT-proBNP

  17. Estimated glomerular filtration rate [ Time Frame: 6 months after index PCI ]
    Kidney function

  18. Cardiac death or re-hospitalization due to heart failure [ Time Frame: 6 months after index PCI ]
    a composite of cardiac death or re-hospitalization due to heart failure

  19. All-cause death or re-hospitalization due to heart failure [ Time Frame: 6 months after index PCI ]
    a composite of all-cause death or re-hospitalization due to heart failure

  20. Target lesion failure [ Time Frame: 6 months after index PCI ]
    a composite of cardiac death, MI, or clinically indicated target-lesion revascularization

  21. Target vessel failure [ Time Frame: 6 months after index PCI ]
    a composite of cardiac death, MI, or clinically indicated target-vessel revascularization

  22. All-cause death [ Time Frame: 6 months after index PCI ]
    All-cause death during follow-up

  23. Cardiac death [ Time Frame: 6 months after index PCI ]
    Cardiac death during follow-up

  24. Target vessel MI [ Time Frame: 6 months after index PCI ]
    Target vessel MI during follow-up

  25. Target lesion revascularization [ Time Frame: 6 months after index PCI ]
    Target lesion revascularization during follow-up

  26. Re-hospitalization due to heart failure [ Time Frame: 6 months after index PCI ]
    Re-hospitalization due to heart failure during follow-up

  27. Any re-hospitalization [ Time Frame: 6 months after index PCI ]
    Any re-hospitalization during follow-up



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04899479


Contacts
Layout table for location contacts
Contact: Young Bin Song, MD, PhD 82-2-3410-1246 youngbin.song@gmail.com
Contact: Ki Hong Choi, MD 82-2-3410-6653 cardiokh@gmail.com

Sponsors and Collaborators
Samsung Medical Center
Layout table for additonal information
Responsible Party: Young Bin Song, Professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT04899479    
Other Study ID Numbers: PRESTIGE-AMI
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: May 28, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The data, analytic methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Young Bin Song, Samsung Medical Center:
Percutaneous Coronary Intervention
Infarct size
Cardiac Magnetic Resonance Imaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Molecular Mechanisms of Pharmacological Action
Heart Failure
Myocardial Infarction
Infarction
Heart Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Vascular Diseases
Sodium-Glucose Transporter 2 Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs