LCZ696 in Advanced LV Hypertrophy and HFpEF

NCT ID: NCT03928158

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2023-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Heart Failure; Essential Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

LCZ 696

Intervention Type: DRUG

50-100-200 mg tablet

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)

Group Type: ACTIVE_COMPARATOR

Valsartan

Intervention Type: DRUG

40-80-160 mg tablet

Interventions

LCZ 696

50-100-200 mg tablet

Intervention Type: DRUG

Valsartan

40-80-160 mg tablet

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

OTHER_GOV

Sponsor Role: lead

Responsible Party

Anastasiia Filatova, MD, PhD

principal investigator, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

National Medical Research Center for Cardiology

Moscow, , Russia

Countries

Russia

Other Identifiers

AAAA-A18-118022290061-2

Identifier Type: -

Identifier Source: org_study_id