A Randomized Controlled Trial of SGLT2 Inhibitors to Improve Left Atrial Function in Patients With Paroxysmal Atrial Fibrillation and Comorbid Hypertension and Abnormal Glucose Metabolism
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- LA strain （LASI）
研究概览
简要总结
Heart failure is the most important clinical endpoint event in atrial fibrillation (AF). Patients with AF complicated by heart failure have a significantly higher risk of all-cause mortality and cardiovascular mortality compared to those without heart failure. Abnormal left atrial function is an important mechanism leading to the occurrence of AF-related heart failure. Therefore, it is essential to find drugs that can improve left atrial function to prevent heart failure in patients with AF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important drugs for regulating metabolic abnormalities. Studies have found that these drugs also reduce the risk of new-onset AF in patients with heart failure. Thus, the investigators hypothesize that SGLT2i may be able to regulate left atrial function.
This study is a multicenter randomized controlled trial using three-dimensional speckle tracking echocardiography to investigate whether SGLT2i can improve left atrial function and prevent heart failure in patients with paroxysmal AF who have hypertension and metabolic disorders, compared to placebo. The investigators also observed the effects of SGLT2i on cardiovascular and metabolic risk factors. The investigator team has a solid foundation in the field of cardiovascular metabolism, having completed the evaluation of left atrial function in paroxysmal AF using three-dimensional speckle tracking technology over the past three years. This study is the first to propose that SGLT2i can improve left atrial function in paroxysmal AF patients with metabolic abnormalities, which is of great significance for preventing heart failure in this type of AF.
详细描述
- Research Methods: This study adopts a multicenter, randomized, placebo-controlled approach, utilizing three-dimensional speckle tracking technology to evaluate the left atrial function of enrolled subjects.
- Research Objectives: Compared with placebo, to observe whether empagliflozin (10mg qd) can improve the left atrial function of patients with paroxysmal atrial fibrillation (AF) who have hypertension and metabolic disorders.
- Research Endpoints:
- Primary Endpoint: Using three-dimensional speckle tracking technology to evaluate the changes in left atrial function of subjects in the empagliflozin group and the placebo group at enrollment and after 12 months of follow-up.
- Evaluation Methods for Primary Endpoint: The left atrial function evaluation of all subjects from all centers will be completed in the echocardiography room of Huashan Hospital. This examination will be conducted in a blinded manner by two experienced echocardiography physicians to assess the left atrial function of the patients, and another two echocardiography physicians will analyze the parameters in a blinded manner.
- Parameters of Left Atrial Function Changes: Left atrial ejection fraction, left atrial ejection volume, left atrial maximum volume, left atrial minimum volume, left atrial pre-systolic volume, left atrial maximum volume index, peak left atrial longitudinal strain, early diastolic left atrial longitudinal strain, late diastolic left atrial longitudinal strain, peak left atrial circumferential strain, early diastolic left atrial circumferential strain, and late diastolic left atrial circumferential strain.
- Secondary Endpoint 1: Record events of subjects visiting or being hospitalized due to heart failure during the follow-up period. This endpoint includes patients who present with symptoms such as dyspnea, fatigue, and orthopnea during the follow-up period, and have an NT-proBNP level greater than 300pg/ml detected in the emergency department, outpatient clinic, or inpatient department, with a documented diagnosis.
- Secondary Endpoint 2: Record the changes in cardiovascular and metabolic risk factors of patients at enrollment and after 12 months of follow-up: blood pressure, blood glucose, uric acid, body weight, and blood lipids. Ensure that the medication use of the enrolled subjects remains unchanged during the follow-up period.
- Randomization and Blinding Arrangements: Use random numbers to randomize the enrolled patients into groups; blind two echocardiography physicians who assess the left atrial function of the subjects and two echocardiography physicians who analyze the left atrial function parameters; blind the subjects; and blind the researchers.
- Follow-up Medication Use:
- Experimental Drug: Dapagliflozin 10mg qd, to be used continuously for 12 months.
- Placebo Drug: A placebo with the same specifications, odor, and color as dapagliflozin, to be used continuously for 12 months.
- Follow-up Duration: 12 months. At enrollment and at the 12th month of follow-up, use three-dimensional speckle tracking technology to complete the left atrial function (evaluated in sinus rhythm) examination of the subjects, and complete the biochemical examinations of blood pressure, blood glucose, blood lipids, body weight, uric acid, etc. Record events of subjects visiting or being hospitalized due to heart failure during the follow-up period.
- Inclusion Criteria:
- Patients aged 18-80 years, treated in the outpatient or inpatient departments of each research center and included in the AF database.
- Patients with paroxysmal AF confirmed by 12-lead electrocardiogram, 24-hour Holter monitoring, or handheld electrocardiogram devices.
- Patients with hypertension who have already started antihypertensive treatment.
- Patients with diabetes who have already started antidiabetic treatment, or patients with prediabetes who have not received antidiabetic treatment but have an HbA1c level within the range of 6.1-6.4% in the past three months.
- Exclusion Criteria:
- Atrial fibrillation caused by severe mitral stenosis.
- Atrial fibrillation with severe mitral regurgitation and severe tricuspid regurgitation.
- Patients who have been clinically diagnosed with heart failure (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction).
- Special types of cardiomyopathy: amyloid cardiomyopathy, Fabry disease, muscular dystrophy, hypertrophic obstructive cardiomyopathy, etc.
- Patients with a history of myocardial infarction within the past three months.
- Pregnant women.
- Withdrawal Criteria:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Patients aged 18-80 years, treated in the outpatient or inpatient departments of each research center and included in the AF database.
- •Patients with paroxysmal AF confirmed by 12-lead electrocardiogram, 24-hour Holter monitoring, or handheld electrocardiogram devices.
- •Patients with hypertension who have already started antihypertensive treatment.
- •Patients with diabetes who have already started antidiabetic treatment, or patients with prediabetes who have not received antidiabetic treatment but have an HbA1c level within the range of 6.1-6.4% in the past three months.
排除标准
- •• Atrial fibrillation caused by severe mitral stenosis.
- •Atrial fibrillation with severe mitral regurgitation and severe tricuspid regurgitation.
- •Patients who have been clinically diagnosed with heart failure (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction).
- •Special types of cardiomyopathy: amyloid cardiomyopathy, Fabry disease, muscular dystrophy, hypertrophic obstructive cardiomyopathy, etc.
- •Patients with a history of myocardial infarction within the past three months.
- •Pregnant women.
研究组 & 干预措施
SGLT2 i TREATMENT
干预措施: SGLT-2 inhibitors (Drug)
PLACEBO
干预措施: Placebo (Drug)
结局指标
主要结局
LA strain （LASI）
时间窗: from enrollment to the end of treatment at 12 months
Using three-dimensional speckle tracking technology to measure longitudinal strain during the reservoir phase (LASr).Using TDI to measure E/e'. The LASI is calculated by these two parameter and can indicate left atrial strain.
次要结局
- circumferential strain (LASr-c)(From enrollment to the end of treatment at 12 months)
- conduit phase (LAScd)(From enrollment to the end of treatment at 12 months)
- hospitalization due to heart failure(From enrollment to the end of treatment at 12 months)
- changes in blood pressure(From enrollment to the end of treatment at 12 months)
- change in blood glucose(From enrollment to the end of treatment at 12 months)
- Change in lipid metabolism(from enrollment to the end of treatment at 12 months)
研究者
Yong Li
Clinical Professor
Huashan Hospital