Sacubitril/Valsartan (LCZ696) in Patients With Advanced Hypertensive Left Ventricular Hypertrophy and Heart Failure With Preserved Ejection Fraction: Clinical, Haemodynamic and Neurohumoral Effects (a Phase 2, Randomized, Single-center, Parallel Group Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Change in 6-minute walking distance (6MWD)
研究概览
简要总结
Patients with advanced LVH and HFpEF will be randomly assigned in open-label fashion to receive LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily, and will be treated for 24 weeks.
详细描述
Heart failure with preserved ejection fraction (HFpEF) has a significant morbidity and mortality, and therapies that have proven effective in HF with reduced EF have not been shown to improve long-term prognosis in HFpEF. Inhibition of circulating neprilysin could augment deficient NP-receptor GC signaling and therefore be beneficial in HFpEF, as suggested by the decrease in NP following administration of valsartan/sacubitril in the phase 2 (PARAMOUNT study). Use of valsartan/sacubitril is currently being tested in the multicenter PARAGON-HF trial with HFpEF patients. The investigators suppose the best candidates for LCZ696 therapy will be patients with HFpEF and advanced concentric LV hypertrophy and obesity, i.e. having the lowest BNP bioavailability.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi ≥109 g/m² in women and ≥132 g/m² in men);
- •New York Heart Association (NYHA) class II-III heart failure;
- •Left ventricular ejection fraction > 50%;
- •Increased LV filling pressures assessed at rest or at peak exercise by echocardiography
- •Body mass index (BMI) > 30 kg/m²
- •Signed and data informed consent
排除标准
- •Age ≤ 18 years;
- •Evidence of myocardial ischemia during stress echocardiography;
- •Chronic atrial flutter or atrial fibrillation;
- •Alternative cause of left ventricular hypertrophy and impaired diastolic function (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis and etc.);
- •NYHA classification I or decompensated heart failure at screening;
- •Systolic blood pressure < 110 mmHg or > 180 mmHg;
- •Diastolic blood pressure < 40 mmHg or > 100 mmHg;
- •Anemia (Hb < 100 g/l);
- •Significant left sided structural valve disease;
- •Secondary hypertension;
- •Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;
- •Myocardial infarction or myocardial revascularization within the last 3 months of screening;
- •Stroke or TIA within the last 3 months of screening;
- •Autoimmunic and oncological diseases;
- •Impaired renal function, defined as eGFR < 30 ml/min/1.73 m²;
- •Impaired liver function;
- •Potassium concentration >5.2 mmol/L.
研究组 & 干预措施
LCZ 696
Initial dose - 50 mg twice daily, up-titration to 200 mg twice daily. Patients will also receive standard therapy for heart failure (β-blockers, diuretics, MRAs)
干预措施: LCZ 696 (Drug)
Valsatran
Initial dose - 40 mg twice daily, up-titration to 160 mg twice daily. Patients also will receive standard therapy for heart failure (β-blockers, diuretics, MRAs)
干预措施: Valsartan (Drug)
结局指标
主要结局
Change in 6-minute walking distance (6MWD)
时间窗: 24 weeks
Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline
次要结局
- Change in exercise time during diastolic stress-test (DST)(24 weeks)
- Change estimated pulmonary artery systolic pressure (PASP)(24 weeks)
- Change in left atrial volume index (LAVI)(24 weeks)
- Change in average E/e' ratio(24 weeks)
- Change in left ventricular mass index (LVMI)(24 weeks)
- Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)(24 weeks)
- Change in high-sensitivity C-reactive protein (hsCRP)(24 weeks)
- Change in carboxyterminal propeptide of type I collagen (PICP)(24 weeks)
- Change of New York Heart Association (NYHA) functional classification(24 weeks)
- Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score(24 weeks)
- Change in carboxyterminal telopeptide of type I collagen (CITP)(24 weeks)
- Change in N-Propeptide Of Type III Procollagen (PIIINP)(24 weeks)
- Change in Growth/differentiation factor 15 (GDF-15)(24 weeks)
- Change in sST2(24 weeks)
- Change in Galectin-3(24 weeks)
- Change in monocyte chemoattractant-1 (MCP-1)(24 weeks)
研究者
Anastasiia Filatova, MD, PhD
principal investigator, MD
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation