Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF)
Heart Failure With Preserved Ejection Fraction
About this trial
This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction focused on measuring Heart failure, preserved ejection fraction, diastolic heart failure
Eligibility Criteria
Inclusion Criteria:
- Left ventricular ejection fraction (LVEF) ≥45% by echo during screening epoch or within 6 months prior to study entry.
- Symptom(s) of heart failure (HF) and requiring treatment with diuretic(s) for HF at least 30 days prior to study entry.
- Current symptom(s) of HF (NYHA class II-IV)
- Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram.
- Elevated NT-proBNP
Exclusion Criteria:
- Any prior measurement of LVEF < 40%.
- Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention within 3 months or and elective PCI within 30 days prior to entry.
- Any clinical event within the 6 months prior to entry could have reduced the LVEF (e.g., MI, CABG), unless an echo measurement performed after the event confirms a LVEF ≥45%.
- Current acute decompensated HF requiring therapy.
- Patients who require treatment with 2 or more of the following: an angiotensin converting enzyme inhibitor (ACEI), an angiotensin receptor blocker (ARB) or a renin inhibitor.
- Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dl, or body mass index (BMI) > 40 kg/m2.
- Systolic blood pressure (SBP) ≥ 180 mmHg at entry, or SBP >150 mmHg and <180 mmHg at entry unless the patient is receiving 3 or more antihypertensive drugs, or SBP < 110 mmHg at entry.
Other protocol-defined inclusion/exclusion criteria may apply.
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Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
LCZ696
Valsartan
Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria. Target dose of LCZ696 during the double blind period is 200 mg b.i.d.
Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria. Target dose of Valsartan during the double blind period is 160 mg b.i.d.