Pleiotropic Effects of Dapagliflozin in Patients With Acute Coronary Syndromes

ConditionsMyocardial Infarction Acute Coronary Syndrome Diabetes Ventricular Dysfunction

Trial statusRecruiting

Trial phasePhase 2, Phase 3

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity of Sao Paulo

About this trial

Type 2 diabetes mellitus (T2DM) is one of the most important risk factors for atherosclerotic heart disease. Strategies focused solely on glycemic control have failed to demonstrate vascular events reduction in this population. On the other hand, new antidiabetic drugs recently have demonstrated significant decrease of cardiovascular mortality, raising the hypothesis that possible effects beyond glycemia control could explain this benefit. Aim: This study is intended to evaluate possible pleiothropic effects of dapaglifozin, a SGLT-2 (sodium glucose cotransporter 2) inhibitor, in individuals admitted with a diagnosis of Acute Myocardial Infarction (AMI). Methods: This is a prospective, randomized, double-blind, placebo controlled trial. Individuals presenting with AMI whithin the first seven days of evolution will be randomized to dapaglifozin or placebo. The investigators's goal is to analyze platelet aggregability 48 hours after randomization (primary endpoint), as well as glycemic control, cardiac biomarkers, corrected QT interval electrocardiographic analysis, autonomic modulation through spectral analysis of the RR interval and inflammatory biomarkers at inclusion and 30 days after starting study drug (secondary endpoints). Sample size calculation resulted in 80 individuals (40 per group). Expected results: This study will seek to aggregate new insights to the current knowledge about this new antidiabetic drug class. Previous randomized clinical trials have demonstrated that SGLT-2 inhibitors significantly reduced the composite endpoint of cardiovascular death, AMI or stroke, as well as Heart Failure (HF) hospitalization. Therefore, this study is supposed to clarify possible mechanisms that could explain these results aforementioned.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Men and women aged ≥ 18 years (women of childbearing age must have a negative pregnancy test);

In routine use of dual antiplatelet therapy with ASA plus an ADP receptor antagonist, according to institutional routines;

Acute myocardial infarction, with or without ST-segment elevation (STEMI/NSTEMI) defined according to the 4th Universal Definition of Acute Myocardial Infarction, with up to 7 days of evolution from the onset of symptoms;

Signature of the Free and Informed Consent Term.

Disqualifiers

Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for a total of 2 years or more during a lifetime at any time;

Current or recent (within 12 months) treatment with rosiglitazone;

Chronic use (>15 consecutive days) of any SGLT2 inhibitor at the time of hospitalization;

Chronic use (>30 consecutive days) with an oral steroid at a dose equivalent to prednisolone ≥10 mg (eg, betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg) per day;

Trial design

Design model

Parallel

Treatments tested in this trial

Placebo
Drug
Patients will be randomized to use dapagliflozin or placebo in a double-blind way
Dapagliflozin
Drug
Patients will be randomized to use dapagliflozin or placebo in a double-blind way

Treatment groups

80 Participants

are divided into 2 treatment groups

Group A: DapagliflozinExperimental treatment 1 intervention

Group B: Placebo groupPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

Platelet aggregation using ADP

To compare platelet aggregation in the dapagliflozin and placebo groups by the Multiplate Analyzer® test (using ADP as an agonist) in hospitalized patients with a diagnosis of AMI within seven days of evolution, using dual antiplatelet therapy with acetylsalicylic acid (ASA) and an anti-platelet ADP, 48 ± 12 hours after starting dapagliflozin/placebo treatment.

Time frame

4 Years

Secondary outcomes

Platelet aggregation using ADP at 30 (± 5) days after study therapy

Compare between the dapagliflozin and placebo groups: platelet aggregability at 30 (± 5) days after study therapy by the Multiplate Analyzer®️ test with ADP , at the same intervals of the analyzes that will be performed with the ADP.

Time frame

4 Years

Platelet aggregation using ASPI at 30 (± 5) days after study therapy

Compare between the dapagliflozin and placebo groups: platelet aggregability at 30 (± 5) days after study therapy by the Multiplate Analyzer®️ test with ASPI, at the same intervals of the analyzes that will be performed with the ADP.

Time frame

4 Years

Other outcomes

Analyze the primary objective of the study in the following pre-specified subgroups:

1. obese (BMI ≥ 30 Kg/m2) and non-obese; 2. male and female sex; 3. elderly (≥ 65 years) and non-elderly; 4. smokers and non-smokers; 5. time since diagnosis of diabetes (≥ or \< 10 years); 6. basal blood glucose ≥ 125 mg/dL and \< 125 mg/dL; 7. glycated hemoglobin (HbA1c) ≤ 9.0% and \> 9.0%; 8. use of clopidogrel or ticagrelor; 9. treatment performed for the acute coronary event: percutaneous coronary intervention or clinical treatment; 10. ejection fraction ≤ 40% and \> 40%. 11. Diabetics and non-diabetics 12. Onset of symptoms ≤ 72 hours and \> 72 hours

Time frame

4 Years

Sponsors and contacts

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University of Sao Paulo

Lead sponsor

Source ClinicalTrials.gov

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