Clinical trial NCT06721442: Effect of Dapagliflozin on Electrocardiographic Parameters in Type 2 Diabetes Patients: DAPA - ECG Study
Official title: Effect of Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, on Ventricular Repolarization Electrocardiographic Parameters in Type 2 Diabetes Patients: DAPA - ECG Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arrhythmias, Cardiac
Diabetes Mellitus
Keywords: Type 2 Diabetes Cardiac Arrhythmias
Dapagliflozin
Ventricular Repolarization
Electrocardiogram
Cardiac Arrhythmias
Lead sponsor: Beneficência Portuguesa de São Paulo
Sponsor class: OTHER
Collaborators: name: Instituto Dante Pazzanese de Cardiologia
First posted: 2024-12-06
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, open-label, controlled trial
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to evaluate whether dapagliflozin can reduce ventricular electrical remodeling, as measured by electrocardiographic parameters, in patients with type 2 diabetes (T2D). The study focuses on understanding how dapagliflozin affects the risk of potentially malignant ventricular arrhythmias and sudden cardiac death in this population.

The main questions it aims to answer are:

* Does dapagliflozin reduce the TpTe interval in patients with T2D?
* Does dapagliflozin impact other electrocardiographic parameters such as QT and QTc intervals, TpTe/QT ratio, and QT dispersion?

Researchers will compare patients treated with dapagliflozin plus optimized medical therapy (OMT) o those receiving OMT without SGLT2 inhibitors to assess whether there is a significant difference in the electrocardiographic parameters and ventricular electrical remodeling.

Participants will:

Be randomized into two groups: one treated with dapagliflozin and the other with optimized medical therapy.

Undergo clinical, electrocardiographic, laboratory, and echocardiographic evaluations at baseline and after three months.

This randomized, prospective, multicenter, open-label study seeks to clarify the cardioprotective mechanisms of dapagliflozin, particularly its impact on ventricular electrical remodeling in patients with type 2 diabetes.

Detailed description: Background: In patients with type 2 diabetes (T2D), hyperglycemia and glycemic variability lead to prolongation and greater heterogeneity of ventricular repolarization, manifested on the electrocardiogram through an increase in QT, QTc, TpeakTend (TpTe) intervals and the TpTe/QT ratio, increasing the risk of potentially malignant arrhythmias. Dapagliflozin has demonstrated efficacy in reducing cardiovascular events in diabetic patients at high cardiovascular risk and in the risk of serious ventricular arrhythmias and sudden cardiac death. However, the exact mechanisms by which dapagliflozin confers this protection have not yet been fully elucidated.

Objective: The main objective of the study was to evaluate the impact of dapagliflozin on the TpTe interval of patients with T2D, and secondarily, it examined its impact on various electrocardiographic parameters such as the QT and QTc intervals, the TpTe/QT ratio, QT dispersion, J-T peak interval, QRS-T angle and heart rate.

Methods: This randomized, prospective, multicenter and open-label study involved 174 patients with T2D, divided into two groups: one treated with dapagliflozin and the other with optimized medical therapy without iSGLT2. Clinical, electrocardiographic, laboratory and echocardiographic evaluations were carried out at the beginning and after three months. The statistical analysis included means, standard deviations, quartiles, and frequencies, with 95% confidence intervals, using Chi-square (or Fisher) and t-Test (or Mann-Whitney) for initial differences, and a linear mixed-effects model to evaluate the results, adopting a significance level of 0.05.

Eligibility criteria: Inclusion Criteria:

* Adult patients (≥18 years old);
* Resting 12-lead electrocardiogram in sinus rhythm;
* Type 2 diabetes;
* Body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, of 45 or less;
* Estimated glomerular filtration rate (eGFR) of at least 30 ml per minute per 1.73 m² of body surface area, according to CKD-EPI criteria;
* Agreed to participate in the study and signed the informed consent form (ICF).

Exclusion Criteria:

* Patients with a QRS interval \> 120 ms;
* Insulin use;
* Atrial fibrillation rhythm;
* Cardiac pacemaker rhythm;
* Planned cardiac surgery or angioplasty within 3 months;
* Glycemic control issues (glucose \> 240 mg/dL) after an overnight fast of 8 hours in both groups;
* Liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 times the upper limit of normal during the baseline phase;
* Medicinal treatment for weight loss within 3 months of the study start;
* Pregnant women, women with delayed menstruation, or those breastfeeding.

Primary outcomes:
measure: Effect of Dapagliflozin on the TpeakTend Interval
timeFrame: 90 days
Secondary outcomes:
measure: Effect of Dapagliflozin on the QT and QTc Interval
timeFrame: 90 days
measure: Effect of Dapagliflozin on the TpTe/QT ratio
timeFrame: 90 days
measure: Effect of Dapagliflozin on the J-Tpeak Interval
timeFrame: 90 days
measure: Effect of Dapagliflozin on the QT interval dispersion (QTd)
timeFrame: 90 days
measure: Effect of Dapagliflozin on The QRS-T angle
timeFrame: 90 days
measure: Effect of Dapagliflozin on the Heart rate
timeFrame: 90 days
Other outcomes:
measure: Glycated hemoglobin (HbA1c)
timeFrame: 90 days
measure: Weight
timeFrame: 90 days
measure: Body Mass Index (BMI)
timeFrame: 90 days
measure: Systolic and Diastolic Blood Pressure
timeFrame: 90 days
measure: Glomerular Filtration Rate
timeFrame: 90 days
measure: Echocardiographic - Left ventricular ejection fraction (LVEF),
timeFrame: 90 days
measure: Echocardiographic - Left ventricular end-diastolic diameter (LVEDD)
timeFrame: 90 days
measure: Echocardiographic - Left ventricular systolic diameter (LVSD)
timeFrame: 90 days
measure: Echocardiographic - Left atrial diameter (LAD)
timeFrame: 90 days
measure: Key Medications in Use
timeFrame: 90 days
measure: Hospitalization Within 90 Days
timeFrame: 90 days
measure: All-Cause Mortality
timeFrame: 90 days
measure: Cause of Death (Cardiovascular or Non-Cardiovascular)
timeFrame: 90 days
Locations:
city: São Paulo
country: Brazil
facility: Hospital Beneficencia Portuguesa de São Paulo
state: SP
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
state: SP
Study officials:
References: