LCZ696 in Advanced LV Hypertrophy and HFpEF

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation61 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Heart Failure Essential Hypertension

Interventions

LCZ 696DRUG

50-100-200 mg tablet

ValsartanDRUG

40-80-160 mg tablet

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi ≥109 g/m² in women and ≥132 g/m² in men); 2. New York Heart Association (NYHA) class II-III heart failure; 3. Left ventricular ejection fraction \> 50%; 4. Increased LV filling pressures assessed at rest or at peak exercise by echocardiography 5. Body mass index (BMI) \> 30 kg/m² 6. Signed and data informed consent Exclusion Criteria: 1. Age ≤ 18 years; 2. Evidence of myocardial ischemia during stress echocardiography; 3. Chronic atrial flutter or atrial fibrillation; 4. Alternative cause of left ventricular hypertrophy and impaired diastolic function (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis and etc.); 5. NYHA classification I or decompensated heart failure at screening; 6. Systolic blood pressure \< 110 mmHg or \> 180 mmHg; 7. Diastolic blood pressure \< 40 mmHg or \> 100 mmHg; 8. Anemia (Hb \< 100 g/l); 9. Significant left sided structural valve disease; 10. Secondary hypertension; 11. Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases; 12. Myocardial infarction or myocardial revascularization within the last 3 months of screening; 13. Stroke or TIA within the last 3 months of screening; 14. Autoimmunic and oncological diseases; 15. Impaired renal function, defined as eGFR \< 30 ml/min/1.73 m²; 16. Impaired liver function; 17. Potassium concentration \>5.2 mmol/L.

Locations (1)

National Medical Research Center for Cardiology

Moscow, Russia

Outcomes

Primary Outcomes

Change in 6-minute walking distance (6MWD)

Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Secondary Outcomes

Change in exercise time during diastolic stress-test (DST)

Difference in exercise time during DST between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Change in left atrial volume index (LAVI)

Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Change in average E/e' ratio

Difference in E/e' ratio assessed by echocardiography both at rest and at peak exercise during diastolic stress test (DST) between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Change estimated pulmonary artery systolic pressure (PASP)

Difference in PASP assessed by echocardiography at peak exercise both at rest and at peak exercise during diastolic stress test (DST) between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Change in left ventricular mass index (LVMI)

Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Change of New York Heart Association (NYHA) functional classification

Difference in NYHA class between 24 weeks after baseline and at baseline

Time frame: 24 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.