A 24-week, randomized, double-blind, multi-center, parallel group, active controlled study to evaluate the effect of LCZ696 on NT-proBNP, exercise capacity, symptoms and safety compared to individualized medical management of comorbidities in patients with heart failure and preserved ejection fractio
- Conditions
- heartfailure10019280
- Registration Number
- NL-OMON46419
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 60
- 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 hypertension;Other protocol-defined inclusion criteria may apply.
- 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 (e.g. 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 visit 1
- 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/m2.
- 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
- eGFR<15 ml/min/1.73 m2 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 childbearing potential unless they are using highly effective methods of contraception.
Other protocol-defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- NT-proBNP at Week 12<br /><br>- Exercise capacity by the six-minute walk test (6MWT) at Week 24</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Mean change from baseline in Kansas City Cardiomyophathy Questionnaire (KCCQ)<br /><br>clinical summary score (CSS) at week 24<br /><br>- Proportion of patients with equal or larger than 5 points change in KCCQ CSS<br /><br>at week 24<br /><br>- Improvement in NYHA functional class at week 24<br /><br>- Improvement in symptoms as assessed by the SF-36 physical component summary<br /><br>(PCS) score at week 24.</p><br>