LCZ696 in Advanced LV Hypertrophy and HFpEF

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

Status and phase: Completed; Phase 2

Conditions: Essential Hypertension; Heart Failure

Treatments: Drug: LCZ 696; Drug: Valsartan

Study type: Interventional

Funder types: Other

Identifiers

NCT03928158

AAAA-A18-118022290061-2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 61 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

61 participants in 2 patient groups

LCZ 696

Experimental group

Description:

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)

Treatment:

Drug: LCZ 696

Valsatran

Active Comparator group

Description:

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)

Treatment:

Drug: Valsartan