Effect of Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, on Ventricular Repolarization Electrocardiographic Parameters in Type 2 Diabetes Patients: DAPA - ECG Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 174
- 试验地点
- 2
- 主要终点
- Effect of Dapagliflozin on the TpeakTend Interval
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
盲法说明
All eligible patients were randomized into two groups using the REDCap software: one group received dapagliflozin combined with optimized medical treatment, while the other group received only the optimized treatment. Each group included 87 patients. To minimize bias in the open-label design, electrocardiograms performed at baseline and at the final visit were evaluated by external independent examiners blinded to group allocation. The Kappa index was used to ensure data consistency and reliability. These measures provided greater rigor and validity to the study results.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Dapafliflozin
A total of 174 individuals were assessed for eligibility, of whom 87 were randomized to receive dapagliflozin in combination with optimized medical treatment for type 2 diabetes.
干预措施: Dapagliflozin (DAPA) (Drug)
结局指标
主要结局
Effect of Dapagliflozin on the TpeakTend Interval
时间窗: 90 days
In the intervention group (dapagliflozin), 12-lead electrocardiograms (ECGs) were performed during designated outpatient visits, with the initial baseline recording conducted at visit 1 (day 0) and the subsequent recording at the final visit, approximately 90 days after the study began. The ECGs were obtained using Micromed electronic equipment, configured with a paper speed of 25 mm/s and an amplitude of 10 mm/mV, ensuring standardized measurements. The ECG intervals were manually measured using Wincardio software (version 11.1.0.0). The primary outcome, the interval between the peak of the T wave and the end of the T wave (TpTe), was assessed to evaluate the effect of dapagliflozin. This assessment compared the two time points (baseline and follow-up), with all ECGs analyzed by an independent external examiner to ensure objectivity and reliability of the study results.
次要结局
- Effect of Dapagliflozin on the QT and QTc Interval(90 days)
- Effect of Dapagliflozin on the TpTe/QT ratio(90 days)
- Effect of Dapagliflozin on the J-Tpeak Interval(90 days)
- Effect of Dapagliflozin on the QT interval dispersion (QTd)(90 days)
- Effect of Dapagliflozin on The QRS-T angle(90 days)
- Effect of Dapagliflozin on the Heart rate(90 days)
研究者
Rodrigo Noronha Campos
Doctor-cardiologist
Beneficência Portuguesa de São Paulo