Pleiotropic Effects of Dapagliflozin in Patients With Acute Coronary Syndromes

NCT06286878 | Recruiting Phase 2

• 1 other identifier: SDC 4620/17/120
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myocardial Infarction; Acute Coronary Syndrome; Diabetes; Ventricular Dysfunction

Outcome Measures

Primary Outcomes (1)

• 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.

  4 Years

Secondary Outcomes (2)

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

  4 Years

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

  4 Years

Other Outcomes (1)

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

  4 Years

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10 mg tablets given once daily, per oral use

Drug: Dapagliflozin

Placebo group

PLACEBO COMPARATOR

Placebo tablets given once daily, per oral use

Drug: Placebo

Interventions

Placebo DRUG

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

Placebo group

Dapagliflozin DRUG

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

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Systolic BP \> 180 or diastolic BP \> 100 mmHg at randomization;
• Diagnosis of Type 1 diabetes mellitus, MODY (maturity onset diabetes of the Young) or diabetes mellitus secondary to diverse endocrinopathy, pancreatic resection, medication, pancreas neoplasia or chronic pancreatitis;
• History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time;
• History of any other malignancy within 5 years (with the exception of skin cancers successfully treated non-melanoma);
• Chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year);
• Any condition that, in the opinion of the Investigator, may render the research participant unfit to complete the study, including, but not limited to, cardiovascular disease (KILLIP \> 2, modified Forester \> IIa,35 recurrent ventricular arrhythmias) or non cardiovascular (eg, active malignancy other than basal cell carcinoma, cirrhosis, chronic lung disease, severe autoimmune disease);
• Pregnancy or lactation;
• Active participation in another clinical trial
• Patients with septic shock or severe glycemic decompensation requiring the use of IV insulin at the time of randomization;
• TGP/ALT(Alanine Amino Transferase) \>3x the upper limit of normality (ULN) or total bilirubin \>2.5 x ULN;
• Estimated glomerular filtration rate (GFR) \< 45 ml/min/1.73m² , calculated by MDRD, or kidney transplant;

Sponsors & Collaborators

• University of Sao Paulo: lead

Study Sites (1)

Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo

São Paulo, São Paulo, 05403-900, Brazil

RECRUITING

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• Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

  PMID: 8598068 BACKGROUND

MeSH Terms

Conditions

Myocardial Infarction; Acute Coronary Syndrome; Diabetes Mellitus; Ventricular Dysfunction

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Jose JN Nicolu

  University of Sao Paulo

  STUDY DIRECTOR

Central Study Contacts

Jose JN Nicolau

CONTACT

+55 (11) 2661-5058; jose.nicolau@incor.usp.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single-center, prospective, randomized, double-blind, placebo-controlled clinical study.

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: February 29, 2024
• Study Start: December 8, 2021
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: April 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)