Multicenter, Randomized, Open-label Trial to Assess the Efficacy of Sacubitril/Valsartan vs. Amlodipine/Losartan on Left Ventricular Remodeling in Patients With Chronic Severe Aortic Regurgitation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up
研究概览
简要总结
The purpose of this study is to assess the efficacy of sacubitril-valsartan compared to the combination of ARB/CCB on left ventricular remodeling in patients with chronic aortic valve regurgitation.
详细描述
After being informed consent about the study and potential risk, all patients giving written informed consent will undergo a 1 month screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in an open-label manner in a 1:1 ratio to sacubitril-valsartan or amlodipine/losartan.
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
- 20 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant over 20 years of age who has not been hospitalized for heart failure
- •Participant with hypertension or systolic blood pressure 125 mmHg or higher
- •Participant with chronic severe aortic regurgitation (VCW >0.6cm)
- •Participant with AV regurgitant volume ≥ 60mL or effective regurgitant orifice area ≥ 0.3 cm2
- •Participant with left ventricular ejection fraction ≥ 55%
排除标准
- •A history of hypersensitivity or allergy to clinical trial drugs or similar compounds or ARB/NEP inhibitors
- •History of angioedema
- •Patients with an ascending aorta dilated by more than 55 mm
- •Patients with aortic valve insufficiency due to hereditary aortic disease (Marfan syndrome, Ehlers-Danlos syndrome)
- •Patients with moderate to severe aortic stenosis
- •Patients with claustrophobia or with metallic implants unsuitable for magnetic resonance imaging
- •History of acute heart failure within 6 weeks and dyspnea of NYHA II or higher
- •Symptomatic hypotension or SBP < 100 mmHg at screening
- •Patients with renal failure (Estimated GFR < 30 mL/min/1.73 m2) or on dialysis
- •Significant increase in blood potassium level (Potassium > 5 mmol/L)
- •Blood AST or ALT value is more than twice the upper limit of normal or symptoms and signs of cirrhosis (history of hepatic coma, history of esophageal varices, history of symptomatic ascites)
- •In case of acute coronary syndrome, stroke, thoracic surgery, and percutaneous coronary angioplasty within 3 months
- •If aortic valve surgery is scheduled within the next 6 months
- •In case of severe mitral valve disease
- •Patients with primary hyperaldosteronism
- •If a woman of childbearing potential has not used double contraception
- •Women who are currently pregnant or lactating
- •When it is judged that there are clinically significant abnormalities in physical examination, diagnostic examination, electrocardiogram, etc. at the time of the screening visit
研究组 & 干预措施
Sacubitril-Valsartan Group
Participant start Sacubitril/Valsartan tablet 50mg twice a day and uptitrate to 100mg twice a day. Participants take the maximum dose considering blood pressure for a total of 48 weeks.
干预措施: Sacubitril-valsartan (Drug)
Amlodipine-Losartan group
Participant start amlodipine/losartan 25/2.5mg once a day and uptitrate to 5/100mg once a day. Participants take the maximum dose considering blood pressure for a total of 48 weeks.
干预措施: Amlodipine-losartan (Drug)
结局指标
主要结局
Change of left ventricular end-diastolic volume index from baseline to 12 months follow-up
时间窗: Baseline and month 12
Change = \[LVEDV on CMR at 12 months\]-\[LVEDV on CMR at baseline\]
次要结局
- Change of EROA of aortic valve regurgitation from baseline to 12 months follow-up.(Baseline and month 12)
- Holodiastolic flow reversal in the proximal abdominal aorta and descending thoracic aorta from baseline to 12 months follow-up(Baseline and month 12)
- Change of LV end-systolic volume from baseline to 12 months follow-up.(Baseline and month 12)
- Aortic valve replacement or repair operation(During 12 months after enrollment)
- Change of regurgitant volume of aortic valve regurgitation from baseline to 12 months follow-up.(Baseline and month 12)
- Change of NT-proBNP level from baseline to 12 months follow-up.(Baseline and month 12)
研究者
Eun Kyoung Kim
Assistant Professor
Samsung Medical Center