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Diabetes MellitusSGLT2-I AMINCT05261867

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

An observational study of Diabetes Mellitus and Acute Coronary Syndrome, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 7 sites in 3 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Acute Coronary Syndrome
Type of treatment
Pill or oral medicine
How many people
800 participants
Where
7 sitesin 3 countries
Study dates
Jan 2017to Jan 2023
Phase
Observational
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
  • Adult, Older adult

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.

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

7 sites in 3 countries.

Carmine Pizzi, MD contact

carmine.pizzi@unibo.it

Pizzi Carmine, MD contact

carmine.pizzi@unibo.it

7 sites in 3 countries

Italy5 sites, 5 recruiting

  • Policlinico Sant'Orsola

    Bologna

    Carmine Pizzi, carmine.pizzi@unibo.it

    Luca Bergamaschi

    Recruiting

  • Azienda Ospedaliera Sant'Anna e San Sebastiano, Caserta

    Caserta

    Paolo Calabrò, MD

    Felice Gragnano

    Recruiting

  • ASST Grande Ospedale Metropolitano Niguarda, Milano

    Milan

    Jacopo Andrea Oreglia, MD

    Giuseppe Esposito

    Recruiting

  • Università Vanvitelli, Ospedale Cardarelli, Napoli

    Naples

    Raffaele Marfella, MD

    Celestino Sardu

    Recruiting

  • Azienda Ospedaliero-Universitaria Sant'Andrea, Roma

    Roma

    Giuliano Tocci, MD

    Recruiting

Other trials in Italy

Belgium1 site, 1 recruiting

  • Cardiovascular Center Aalst, OLV-Clinic, Aalst, Belgium

    Aalst, 9300

    Emanuele Barbato, MD

    Pasquale Paolisso

    Recruiting

Other trials in Belgium

Bulgaria1 site, 1 recruiting

  • Alexandrovska University Hospital, Sofia, Bulgaria

    Sofia

    Niya Mileva, MD

    Recruiting

Other trials in Bulgaria

About this study

Official title: 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.

Read the 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.

Keywords
SGLT2-I, Acute myocardial infarction, Diabetes Mellitus, Prognosis
Medical subject headings
Diabetes Mellitus, Acute Coronary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT05261867
Study groupRoleWhat they receive
Diabetic patients treated with SGLT2-IDiabetic 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) agentsDiabetic patients treated with other oral anti-diabetic agents alone.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE).

    Composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE).

    Measured: Through study completion, an average of 2 year

Secondary outcomes (11)

  1. Intra-hospital cardiovascular death

    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.

    Measured: Up to 30 days

  2. Intra-hospital atrial and ventricular arrhythmias

    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.

    Measured: Up to 30 days

  3. Reduction of the infarct size

    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).

    Measured: Up to 30 days

  4. Reduction of the inflammatory response.

    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.

    Measured: Up to 30 days

  5. Contrast-induced acute kidney injury

    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.

    Measured: Through study completion, an average of 1 year

  6. Length of hospital stay

    Length of hospitalization (days)

    Measured: Up to 30 days

  7. All-cause mortality

    All-cause mortality included all causes of death for the population during the follow-up.

    Measured: Through study completion, an average of 2 year

  8. Cardiovascular mortality

    Cardiovascular death consisted of deaths that result from an AMI, sudden cardiac death, heart failure, stroke, and other cardiovascular causes.

    Measured: Through study completion, an average of 2 year.

  9. Heart failure hospitalization.

    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.

    Measured: Through study completion, an average of 2 year.

  10. Recurrent AMI

    Recurrent acute myocardial infarction.

    Measured: Through study completion, an average of 2 year

  11. Any coronary revascularization

    Clinically indicated target vessel revascularization for significant renarrowing.

    Measured: Through study completion, an average of 2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2022
  2. Study startJan 2017
  3. Primary completionNov 2021
  4. Study completionJan 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
800 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05261867
Sponsor's protocol ID
SGLT2I001
Acronym
SGLT2-I AMI
Status last verified
Oct 2022
First submitted
10 Feb 2022
Last updated
24 Oct 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e651. doi: 10.1161/CIR.0000000000000617. No abstract available.

    PubMed 30571511

  • Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013 Jan;123(1):92-100. doi: 10.1172/JCI62874. Epub 2013 Jan 2.

    PubMed 23281415

  • Andreadou I, Bell RM, Botker HE, Zuurbier CJ. SGLT2 inhibitors reduce infarct size in reperfused ischemic heart and improve cardiac function during ischemic episodes in preclinical models. Biochim Biophys Acta Mol Basis Dis. 2020 Jul 1;1866(7):165770. doi: 10.1016/j.bbadis.2020.165770. Epub 2020 Mar 17.

    PubMed 32194159

  • Tanajak P, Sa-Nguanmoo P, Sivasinprasasn S, Thummasorn S, Siri-Angkul N, Chattipakorn SC, Chattipakorn N. Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury. J Endocrinol. 2018 Feb;236(2):69-84. doi: 10.1530/JOE-17-0457. Epub 2017 Nov 15.

    PubMed 29142025

  • Lahnwong C, Palee S, Apaijai N, Sriwichaiin S, Kerdphoo S, Jaiwongkam T, Chattipakorn SC, Chattipakorn N. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovasc Diabetol. 2020 Jun 15;19(1):91. doi: 10.1186/s12933-020-01066-9.

    PubMed 32539724

  • Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017 Mar;104:298-310. doi: 10.1016/j.freeradbiomed.2017.01.035. Epub 2017 Jan 26.

    PubMed 28132924

  • Sayour AA, Celeng C, Olah A, Ruppert M, Merkely B, Radovits T. Sodium-glucose cotransporter 2 inhibitors reduce myocardial infarct size in preclinical animal models of myocardial ischaemia-reperfusion injury: a meta-analysis. Diabetologia. 2021 Apr;64(4):737-748. doi: 10.1007/s00125-020-05359-2. Epub 2021 Jan 23.

    PubMed 33483761

  • Paolisso P, Bergamaschi L, Gragnano F, Gallinoro E, Cesaro A, Sardu C, Mileva N, Foa A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Esposito G, Morici N, Andrea OJ, Casella G, Mauro C, Vassilev D, Galie N, Santulli G, Marfella R, Calabro P, Pizzi C, Barbato E. Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry. Pharmacol Res. 2023 Jan;187:106597. doi: 10.1016/j.phrs.2022.106597. Epub 2022 Dec 5.

    PubMed 36470546

  • Cesaro A, Gragnano F, Paolisso P, Bergamaschi L, Gallinoro E, Sardu C, Mileva N, Foa A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Esposito G, Morici N, Oreglia JA, Casella G, Mauro C, Vassilev D, Galie N, Santulli G, Pizzi C, Barbato E, Calabro P, Marfella R. In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study. Front Cardiovasc Med. 2022 Sep 27;9:1012220. doi: 10.3389/fcvm.2022.1012220. eCollection 2022.

    PubMed 36237914

  • Paolisso P, Bergamaschi L, Santulli G, Gallinoro E, Cesaro A, Gragnano F, Sardu C, Mileva N, Foa A, Armillotta M, Sansonetti A, Amicone S, Impellizzeri A, Casella G, Mauro C, Vassilev D, Marfella R, Calabro P, Barbato E, Pizzi C. Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry. Cardiovasc Diabetol. 2022 May 15;21(1):77. doi: 10.1186/s12933-022-01506-8.

    PubMed 35570280

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes Mellitus and Acute Coronary Syndrome, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 7 sites in 3 countries.

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 3 inclusion and 6 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 24 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Italy, Belgium, Bulgaria. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

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?

Contact Carmine Pizzi, MD (carmine.pizzi@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). (time frame: Through study completion, an average of 2 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05261867, which also lists 10 linked publications.

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 24 Oct 2022.

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