"An Open-label Clinical Trial to Evaluate the Safety and Efficacy of Empagliflozin and Sacubitril/Valsartan in Adult Patients With Chronic Heart Failure With Reduced Ejection Fraction Associated With Congenital Heart Disease"
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- 3D echocardiographic systemic ventricular end-systolic volume index
研究概览
简要总结
The treatment of adult patients with congenital heart disease (ACHD) and heart failure (HF) represents a great challenge since, to date, there is no standardized guideline for this specific population. Although new treatments for HF have been proposed, such as Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors and neprilisin and angiotensin receptor inhibitors, the benefit of these drugs in patients with HF associated with congenital heart disease in adults has not yet been demonstrated. For this reason, this study pretends to evaluate the efficacy of empagliflozin and sacubitril/valsartan in this population.
详细描述
A 12-week randomized, open label, active-controlled trial to explore the effects of once-daily empagliflozin 10 mg and/or sacutril/valsartan 49 mg/51 mg in the reduction of systemic ventricular volumes (end-diastolic and end-systolic) in adult patients with HF associated with congenital heart disease.
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
- None
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
- •NYHA functional class II-IV
- •Diagnosis of CHD: repaired, palliated or without previous treatment
- •Systemic ventricular ejection fraction <40%
- •Without unplanned hospital admissions within 3 months prior to randomization
- •The participant is willing and able to give informed consent for participation in the study
排除标准
- •Pregnant and postpartum women
- •Breastfeeding women during the study
- •History of drug allergy to any SGLT-2 inhibitor and/or sacubitril/valsartan
- •Previous administration of a drug regimen including an SGLT-2 inhibitor and/or sacubitril/valsartan
- •Intellectual or physical disability that impedes the subject to perform the 6 minute walk-test
- •Patients with any contraindication to SGLT-2 inhibitor and/or sacubitril/valsartan
- •Medical history of myocardial infarction, cardiac surgery or fulminant myocarditis within the last three months
- •Medical history of type 1 diabetes mellitus
- •Medical history of hypertensive crisis in the previous 6-months
- •Medical history of cardiogenic shock or heart failure decompensation in the previous 6-months
- •Medical history of heart transplantation
研究组 & 干预措施
Conventional treatment of Heart failure and Sacubitril/Valsartan
Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours.
Additionally, patients will receive Sacubitril/Valsartan, with the intention to titrate up to 49 mg/51 mg orally every 12 hours.
干预措施: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID (Drug)
Conventional treatment plus Empagliflozin and Sacubitril/valsartan
Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours.
Additionally, patients will use Sacubitril/Valsartan, with the intention to titrate up to 49 mg/51 mg orally every 12 hours and Empagliflozin 10 mg orally every 24 hours.
干预措施: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID (Drug)
Conventional treatment plus Empagliflozin and Sacubitril/valsartan
Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours.
Additionally, patients will use Sacubitril/Valsartan, with the intention to titrate up to 49 mg/51 mg orally every 12 hours and Empagliflozin 10 mg orally every 24 hours.
干预措施: Empagliflozin 10 MG OD (Drug)
Conventional treatment plus Empagliflozin
Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours.
Additionally, patients will use Empagliflozin 10 mg orally every 24 hours.
干预措施: Empagliflozin 10 MG OD (Drug)
结局指标
主要结局
3D echocardiographic systemic ventricular end-systolic volume index
时间窗: Twelve weeks
Change of 6.0 ml or greater in end-systolic volume index measured by 3D echocardiogram.
3D echocardiographic systemic ventricular end-diastolic volume index
时间窗: Twelve weeks
Change of 8.2 ml or greater in systemic ventricular end-diastolic volume index measured by 3D echocardiogram.
次要结局
- Functional class(Twelve weeks)
- Pulmonary congestion(Twelve weeks)
- 6-minute walking test(Twelve weeks)
- Echocardiographic ejection fraction from the systemic ventricle(Twelve weeks)
- NT-proBNP(Twelve weeks)
- Systemic venous congestion(Twelve weeks)
- Echocardiographic longitudinal overall strain(Twelve weeks)