A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients

• Status: Completed
• Trial end date: 2019-10-28
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to demonstrate the superiority of LCZ696 over individualized medical therapy for comorbidities in reducing N-terminal pro-brain natriuretic peptide (NT-proBNP) and improving exercise capacity and HF symptoms in patients with heart failure with preserved ejection fraction (HFpEF).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Enalaprilat; LCZ 696; Sacubitril and valsartan sodium hydrate drug combination; Valsartan

Criteria

Inclusion Criteria:

• Left ventricular ejection fraction (LVEF) >40% by echo within 6 months prior to study entry or during the screening epoch

• Symptom(s) of heart failure (HF) requiring treatment with diuretics (including loop, or thiazide diuretics, or mineralocorticoid antagonist [MRAs]) for at least 30 days prior to study entry

• NYHA class II-IV

• Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram.

• NT-proBNP > 220 pg/mL for patients with no atrial fibrillation/atrial flutter (AF) or >600 pg/mL for patients with AF

• KCCQ clinical summary score < 75

• Patients on ACEi or ARB therapy must have a history of HTN

Exclusion Criteria:

• Any prior measurement of LVEF ≤ 40%, under stable conditions

• Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention (PCI) within 3 months or an elective PCI within 30 days prior to study entry

• Any clinical event within the 6 months prior to Visit 1 that could have reduced the LVEF (eg MI, coronary artery bypass graft [CABG]), unless an echo measurement was performed after the event confirming the LVEF to be >40%

• Current (within 30 days from Visit 1) acute decompensated HF requiring therapy.

• Current (within 30 days from Visit 1) use of renin inhibitor(s), dual RAS blockade or LCZ696

• History of hypersensitivity to LCZ696 or its components

• Patients with a known history of angioedema

• Walk distance primarily limited by non-cardiac comorbid conditions at study entry

• Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dL males and < 9.5 g/dL females, or body mass index (BMI) > 40 kg/m^2.

• Systolic blood pressure (SBP) ≥ 180 mmHg at study entry, or SBP >150 mmHg and <180 mmHg at study entry unless the patient is receiving 3 or more antihypertensive drugs, or SBP < 110 mmHg at study entry.

• Patients with HbA1c > 7.5% not treated for diabetes

• Patients with prior major organ transplant or intent to transplant (ie on transplant list)

• eGFR < 30 ml/min/1.73 m^2 as measured by MDRD at screening

• Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at study entry

• History or presence of any other disease with a life expectancy of < 3 years

• Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception

Other protocol-defined inclusion/exclusion criteria may apply.