Cardioprotective Effect of SGLT2-I in Diabetic Patients With AMI (SGLT2-I AMI PROTECT Study) (SGLT2-I AMI)

October 20, 2022 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Cardioprotective Effect of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-I) in Diabetic Patients With Acute Myocardial Infarction

Despite their potential benefits on the heart with pleiotropic mechanisms, the cardioprotective effects of new glucose-lowering SGLT-2 inhibitors in patients with myocardial infarction - both in the acute and chronic phase - have never been explored.

The key point of the project will be the evaluation of the cardioprotective effect and the potential prognostic benefit of SGLT-2 inhibitors in patients with diabetes and acute myocardial infarction.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Classically, the physiopathology of myocardial infarction is linked to the presence of coronary atherosclerosis. According to the European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines of the fourth Universal definition, type 1 myocardial infarction (MI), the most frequent cause was atherothrombotic plaque (the mechanism of plaque erosion, rupture, fissuring with an athero-thrombotic)(1) In acute myocardial infarction, early restoration of epicardial and myocardial blood flow is of paramount importance to limit infarction size and create optimum conditions for favorable long-term outcome. Currently, restoration of epicardial blood flow is preferably and effectively obtained by primary percutaneous coronary intervention (PPCI). After opening the occluded artery, however, the reperfusion process itself causes damage to the myocardium, the so called "reperfusion injury". The phenomenon of reperfusion injury is incompletely understood and currently there is no established therapy for preventing it. Contributory factors are intramyocardial edema with compression of the microvasculature, oxidative stress, calcium overload, mitochondrial transition pore opening, micro embolization, neutrophil plugging and hyper contracture. This results in myocardial stunning, reperfusion arrhythmias and ongoing myocardial necrosis (2,3). There is general agreement that a large part of the cell death caused by myocardial reperfusion injury occurs during the first few minutes of reperfusion, and that early treatment is required to prevent it.

According to current guidelines, drug therapy administrated for acute myocardial infarction includes antiplatelets (against atherosclerotic plaque and stent thrombosis), renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers and lipid-lowering therapy (primarily with statins).

Due to their high efficacy, excellent tolerability, and their ability to reduce major adverse cardiovascular events in large clinical trials, SGLT2 inhibitors have been tested in a variety of preclinical studies and it was demonstrated to reduce acute myocardial ischemia-reperfusion (I/R) injury (4).

Four-week pre-treatment with dapagliflozin could decrease infarct size in rats with obese insulin resistance which underwent cardiac ischemic-reperfusion injury (5) and a recent experimental study demonstrated that acute dapagliflozin administration during cardiac I/R injury exerted cardioprotective effects by attenuating cardiac infarct size, increasing left ventricular function and reducing arrhythmias (6). Moreover, in rats with previous myocardial infarct, dapagliflozin treatment beginning one day after left anterior descending coronary artery ligation could decrease myofibroblast infiltration and myocardial fibrosis (7).

Finally, a preregistered meta-analysis (PROSPERO), that included placebo-controlled, interventional studies of small and large animal models of myocardial ischaemia-reperfusion injury, testing the effect of SGLT2 inhibitor treatment on myocardial infarct size concluded that the glucose-lowering SGLT2 inhibitors reduce myocardial infarct size in animal models independent of diabetes status (8).

Despite its potential benefits on the heart with pleiotropic mechanisms, the cardioprotective effects of new glucose-lowering SGLT-2 inhibitors in patients with myocardial infarction - both in the acute and chronic phase- have never been explored.

The key point of the project will be the evaluation of the cardioprotective effect and the potential prognostic benefit of SGLT-2 inhibitors in patients with diabetes and acute myocardial infarction.

The investigators' findings could provide significant insights for future clinical trials on SGLT-2 inhibitors treatments in patients with ischemic heart disease.

Study Type

Observational

Enrollment (Anticipated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Aalst, Belgium, 9300
        • Recruiting
        • Cardiovascular Center Aalst, OLV-Clinic, Aalst, Belgium
        • Contact:
          • EMANUELE BARBATO, MD
        • Sub-Investigator:
          • Pasquale Paolisso
        • Sub-Investigator:
          • Emanuele Gallinoro
  • Bulgaria
      • Sofia, Bulgaria
        • Recruiting
        • Alexandrovska University Hospital, Sofia, Bulgaria
        • Contact:
          • Niya Mileva, MD
  • Italy
      • Bologna, Italy
        • Recruiting
        • Policlinico Sant'Orsola
        • Contact:
        • Sub-Investigator:
          • Luca Bergamaschi
        • Sub-Investigator:
          • Alberto Foà
      • Caserta, Italy
        • Recruiting
        • Azienda Ospedaliera Sant'Anna e San Sebastiano, Caserta
        • Contact:
          • Paolo Calabrò, MD
        • Sub-Investigator:
          • Felice Gragnano
        • Sub-Investigator:
          • Arturo Cesaro
      • Milan, Italy
        • Recruiting
        • ASST Grande Ospedale Metropolitano Niguarda, Milano
        • Contact:
          • Jacopo Andrea Oreglia, MD
        • Sub-Investigator:
          • Giuseppe Esposito
      • Napoli, Italy
        • Recruiting
        • Università Vanvitelli, Ospedale Cardarelli, Napoli
        • Contact:
          • Raffaele Marfella, MD
        • Sub-Investigator:
          • Celestino Sardu
      • Roma, Italy
        • Recruiting
        • Azienda Ospedaliero-Universitaria Sant'Andrea, Roma
        • Contact:
          • Giuliano Tocci, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Consecutive patients with STEMI/NSTEMI diagnosed according to ESC guidelines undergoing reperfusion treatment with percutaneous transluminal coronary angioplasty (PTCA) with known type II diabetes mellitus treated with oral antidiabetic drugs.

Description

Inclusion Criteria:

  • Age ≥18 y old
  • STEMI/NSTEMI diagnosed according to ESC guidelines undergoing reperfusion treatment with percutaneous transluminal coronary angioplasty (PTCA).
  • Known type II diabetes mellitus treated with oral antidiabetic drugs

Exclusion Criteria:

  • Type I diabetes mellitus or type II diabetes mellitus treated only with insulin therapy alone or in combination with other anti-diabetic drugs.
  • Patients treated with Coronary artery bypass grafting (CABG) after the coronary angiography (CAG) (NSTEMI)
  • Previous CABG
  • Severe valvular heart disease.
  • Contraindications for secondary medical prevention therapy approved for myocardial infarctions, like beta-blockers, angiotensin-converting enzyme inhibitor(ACEI )/angiotensin receptor blocker (ARBs), antiplatelets, statins. All patients will be treated with optimal secondary prevention therapy suggested by the current ESC guidelines.
  • Patients who start SGLT2 therapy after the acute index event.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Diabetic patients treated with SGLT2-I
Diabetic patients treated with SGLT2-I alone or in combination with other oral anti-diabetic (OAD) agents. Patients were considered in the SGLT2-I group if it was started at least 1 month prior to index hospitalization.
Diabetic patients treated with other oral anti-diabetic (OAD) agents
Diabetic patients treated with other oral anti-diabetic agents alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE).
Time Frame: Through study completion, an average of 2 year
Composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE).
Through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intra-hospital cardiovascular death
Time Frame: Up to 30 days
Intra-hospital cardiovascular death mortality included deaths that result from an AMI, sudden cardiac death, heart failure, stroke, and other cardiovascular causes during the hospitalization.
Up to 30 days
Intra-hospital atrial and ventricular arrhythmias
Time Frame: Up to 30 days
Ventricular arrhythmias were defined as a cardiac arrhythmia of three or more consecutive complexes originating from the ventricles at a rate of greater than 100 beats per minute. We included both sustained (lasting 30 sec or more) and non-sustained (lasting less than 30 sec) ventricular arrhythmias due to similar risk of adverse cardiovascular outcomes associated with both these types.
Up to 30 days
Reduction of the infarct size
Time Frame: Up to 30 days
Myocardial infarct size was estimated using high-sensitivity troponin (at the moment of hospital admission and every 3-6 hours thereafter for the following 24 hours) and the left ventricular end-diastolic volume (LVEDV) and the biplane left ventricular ejection fraction (LVEF).
Up to 30 days
Reduction of the inflammatory response.
Time Frame: Up to 30 days
The inflammatory response was evaluated using the following parameters: C reactive protein (CRP), white blood cells - leukocytes and neutrophils count, neutrophil to lymphocyte ratio (NLR), neutrophil to platelet ratio (NPR), platelet to lymphocytes ratio (PLR), C-Reactive Protein. In particular, NLR is the ratio of neutrophil and lymphocyte counts, NPR is the ratio of neutrophil and platelet counts, and PLR is obtained by dividing the platelet count by the lymphocytes. Patients with concomitant basal values of CRP and NLR above the median were considered to have an inflammatory response.
Up to 30 days
Contrast-induced acute kidney injury
Time Frame: Through study completion, an average of 1 year
Contrast-induced acute kidney injury is defined as an increase in sCr by 0.3 mg/dL or an increase in creatinine to ⩾1.5 times baseline within 3 to 5 days following contrast exposure.
Through study completion, an average of 1 year
Length of hospital stay
Time Frame: Up to 30 days
Length of hospitalization (days)
Up to 30 days
All-cause mortality
Time Frame: Through study completion, an average of 2 year
All-cause mortality included all causes of death for the population during the follow-up.
Through study completion, an average of 2 year
Cardiovascular mortality
Time Frame: Through study completion, an average of 2 year.
Cardiovascular death consisted of deaths that result from an AMI, sudden cardiac death, heart failure, stroke, and other cardiovascular causes.
Through study completion, an average of 2 year.
Heart failure hospitalization.
Time Frame: Through study completion, an average of 2 year.
Heart failure re-hospitalization was evaluated according to the ESC Guidelines and consisted of unscheduled hospital admission for a primary diagnosis of HF in which the patient presented typical signs, symptoms, and diagnostic testing consistent with the diagnosis of HF and consequently received HF-directed therapy.
Through study completion, an average of 2 year.
Recurrent AMI
Time Frame: Through study completion, an average of 2 year
Recurrent acute myocardial infarction.
Through study completion, an average of 2 year
Any coronary revascularization
Time Frame: Through study completion, an average of 2 year
Clinically indicated target vessel revascularization for significant renarrowing.
Through study completion, an average of 2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Collaborators

University of Campania "Luigi Vanvitelli"
Niguarda Hospital
VZW Cardiovascular Research Center Aalst
Azienda Ospedaliera "Sant'Andrea"
Alexandrovska University Hospital
Cardarelli Hospital
ASST Grande Ospedale Metropolitano Niguarda
Maggiore Hospital Carlo Alberto Pizzardi
Azienda Ospedaliera Sant'Anna e San Sebastiano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Actual)

November 1, 2021

Study Completion (Anticipated)

January 1, 2023

Study Registration Dates

First Submitted

February 10, 2022

First Submitted That Met QC Criteria

February 28, 2022

First Posted (Actual)

March 2, 2022

Study Record Updates

Last Update Posted (Actual)

October 24, 2022

Last Update Submitted That Met QC Criteria

October 20, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGLT2I001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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