Phase 3
N=2,572
A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients
Heart Failure With Preserved Ejection Fraction
Bottom Line
View on ClinicalTrials.gov: NCT03066804 ↗Enrolled (actual)
2,572
Serious AEs
14.7%
Results posted
Feb 2021
Primary outcome: Primary: Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Week 12 — 0.8218; 0.9828 Ratio — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- sacubitril/valsartan (Drug); Enalapril (Drug); Valsartan (Drug); Placebo to match sacubitril/valsartan (Drug); Placebo to match enalapril (Drug); Placebo to match valsartan (Drug)
- Age
- Adult, Older Adult · 45+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Week 12 |
0.8218; 0.9828 | <0.0001 sig |
| PRIMARY Change From Baseline in 6 Minute Walk Distance (6MWD) at Week 24 |
9.6935; 12.1920 | 0.4164 |
| SECONDARY Mean Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at Week 24 |
12.3399; 11.8168 | 0.4791 |
| SECONDARY Percentage of Patients With ≥ 5-points Deterioration in KCCQ Clinical Symptom Score(CSS) at Week 24 |
15.49; 16.69 | 0.5294 |
| SECONDARY Percentage of Patients With ≥ 5-points Improvement in KCCQ Clinical Symptom Score(CSS) at Week 24 |
67.94; 65.70 | 0.4938 |
| SECONDARY Change From Baseline in NYHA Functional Class at Week 24 |
23.62; 24.00; 72.23; 71.68; 4.15; 4.31 | 0.8314 |
| SECONDARY Change From Baseline in The Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24 |
2.5405; 2.6975 | 0.6370 |
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).
Eligibility 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 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) 40 kg/m^2.
- Systolic blood pressure (SBP) ≥ 180 mmHg at study entry, or SBP >150 mmHg and 7.5% not treated for diabetes
- Patients with prior major organ transplant or intent to transplant (ie on transplant list)
- eGFR 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.
Data sourced from ClinicalTrials.gov (NCT03066804). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.