The Use of Empagliflozin in Patients With Hypertrophic Cardiomyopathy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 250
- 试验地点
- 2
- 主要终点
- Primary Outcome: Change in peak VO2 measured in the cardiopulmonary exercise testing AND Change in 23-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) range from 0 to 100, with higher scores indicating better health status.
研究概览
简要总结
The proposed intervention will be administration of empagliflozin at a standard dose of 10 mg daily for a period of 12 months. Patients with diagnosed diabetes will be excluded from the study. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group. The primary endpoint of the study will be the change in peak oxygen uptake (VO2 max) measured in a cardiopulmonary exercise test. VO2max is an objective indicator of physical performance and will be evaluated before and after empagliflozin or placebo treatment.
详细描述
Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium. Conventionally, the incidence of this disease was estimated at 1: 500 people, but it is probably higher and amounts to about 1: 200 cases. In Poland, this gives 76,000 to 190,000 people. HCM is asymptomatic in some people. In others, it is associated with progressive left ventricular diastolic dysfunction due to myocardial hypertrophy and fibrosis, eventually leading to systolic dysfunction and progressive heart failure. Both heart failure with preserved left ventricular ejection fraction (LVEF) and reduced LVEF are inevitably associated with impaired physical function, often affecting young, professionally and socially active individuals. An additional significant problem in patients with HCM is arrhythmias leading to an increased risk of sudden death.
At present, for patients with HCM, there is no treatment available, which could inhibit the progression of the disease. The methods of treatment proposed so far, affecting the various pathogenic mechanisms of hypertrophic cardiomyopathy, have proved to be ineffective.
The aim of the project is therefore to seek a therapeutic solution for a disease for which standard medicine does not yet offer satisfactory solutions.
Empagliflozin is a reversible, potent and selective competitive inhibitor of sodium-glucose co-transporter-2 (SGLT2). It is the main transporter responsible for the reabsorption of glucose from the glomerular filtrate into the bloodstream. Its inhibition in people with type 2 diabetes leads to an increase in urinary glucose excretion and a decrease in its concentration in the blood. In the study in patients with type 2 diabetes and high cardiovascular risk, the use of empagliflozin was associated with a significant decrease in mortality and the number of hospitalizations due to heart failure. The mechanisms responsible for beneficial effects of empagliflozin are not fully understood. It is underlined that effects leading to a reduction of oxidative stress, improvement of diastolic function, inhibition of myocardial fibrosis and, what is important, improvement of myocardial energy status and reduction of cardiomyocyte calcium overload, increase of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity, which are important pathophysiological mechanisms of HCM, leading to progressive myocardial hypertrophy and the development of heart failure.
The proposed intervention will be administration of empagliflozin at a standard dose of 10 mg daily for a period of 12 months. Patients with diagnosed diabetes will be excluded from the study. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group. The primary endpoints of the study will be:
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •written, voluntary informed consent to participate in the study
- •diagnosis of hypertrophic cardiomyopathy
- •age ≥ 18 years
排除标准
- •refusal to consent to participate in the study
- •diagnosis of diabetes
- •patients with hypertrophic obstructive cardiomyopathy requiring interventional treatment (maximal LVOT gradient ≥ 50 mmHg), and who are in III-IV NYHA functional class, despite of the treatment with maximal tolerated doses
- •refusal to consent to participate in the study
- •diagnosis of diabetes
- •patients with hypertrophic obstructive cardiomyopathy requiring interventional treatment (maximal LVOT gradient ≥ 50 mmHg), and who are in III-IV NYHA functional class, despite of the treatment with maximal tolerated doses
- •ICD or cardiac pacemaker (for a group of patients in whom cardiac magnetic resonance study will be performed; n=100)
- •planned implantation of cardiac resynchronization therapy (CRT of CRT-D) in the following 12 months
- •life expectancy below 12 months
- •pregnancy (currently or planned in the following 12 months)
- •breast feeding
- •age below 18 years
- •recurrent genito-urinary tract infections in the past or currently
- •urosepsis in the history
- •Impaired renal function, defined as eGFR < 30 mL/min/1.73 m2 (CKD-EPI)cr or requiring dialysis,
- •other contraindications to the use of empagliflozin
- •musculo-skeletal or neurologic diseases that make it unable to perform cardiopulmonary exercise testing
- •heart transplant recipient or listed for heart transplant
- •implanted left ventricular assist device
- •Any severe (obstructive or regurgitant) valvular heart disease expected to lead to surgery during the trial in the Investigator's opinion
- •Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 1 week from discharge to screening, and during screening period until randomization
- •Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm documented by ECG at screeining
- •Systolic blood pressure (SBP) ≥ 180 mmHg at randomization
- •Symptomatic hypotension and/or a SBP < 100 mmHg at screeining or randomization
- •Chronic pulmonary disease requiring home oxygen, oral steroid therapy or hospitalisation for exacerbation within 12 months, or significant chronic pulmonary disease in the Investigator's opinion, or primary pulmonary arterial hypertension
- •Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) at screening
- •Haemoglobin < 9 g/dl at screening
- •Major surgery (major according to the investigator's assessment) performed within 90 days prior to screening, or scheduled major elective surgery (e.g. hip replacement ) within 90 days after screening
- •Gastrointestinal (GI) surgery or GI disorder that could interfere with absorption of trial medication in the investigator's opinion
- •Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer
- •History of ketoacidosis
- •Patients who must or wish to continue the intake of any drug considered likely to interfere with the safe conduct of the trial
- •Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s)
- •Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial subject or unlikely to complete the trial
- •Any other clinical condition that would jeopardise patients safety while participating in this trial, or may prevent the subject from adhering to the trial protocol
研究组 & 干预措施
Empagliflozin group
Patients in the empagliflozin group will receive 10 mg of empagliflozin once daily for 12 months
干预措施: Empagliflozin 10 MG (Drug)
Control group
Patients in the control group will receive placebo once daily for 12 months
干预措施: Placebo (Drug)
结局指标
主要结局
Primary Outcome: Change in peak VO2 measured in the cardiopulmonary exercise testing AND Change in 23-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) range from 0 to 100, with higher scores indicating better health status.
时间窗: 12 months
Change in peak VO2 measured in the cardiopulmonary exercise testing and Change in 23-item KCCQ-OSS.
次要结局
- Secondary outcome: Change in peak VO2 measured in the cardiopulmonary exercise testing in patients with reduced left ventricular ejection fraction (EF <50%)(12 months)