Phase 4
N=365
EntrestoTM (LCZ696) In Advanced Heart Failure (LIFE Study)
Heart Failure
Bottom Line
View on ClinicalTrials.gov: NCT02816736 ↗Enrolled (actual)
365
Serious AEs
20.9%
Results posted
Dec 2021
Primary outcome: Primary: Change in NT-proBNP — 0.14; 0.19 unitless — p=0.45
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- LCZ696 (Drug); valsartan (Drug); LCZ696 placebo (Drug); valsartan placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Duke University
- Primary completion
- Sep 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in NT-proBNP |
0.14; 0.19 | 0.45 |
| SECONDARY Composite Endpoint of the Effects of LCZ696 (Number of Days) |
108.58; 119.8 | 0.15 |
| SECONDARY Tolerability - Target Dose |
49; 37; 28; 41; 33; 30 | 0.51 |
| SECONDARY Tolerability - Hypotension |
29; 20; 138; 148 | 0.16 |
| SECONDARY Tolerability - Renal Function |
7; 7; 160; 161 | 0.99 |
| SECONDARY Tolerability - Hyperkalemia |
28; 15; 139; 153 | 0.035 sig |
Summary
The primary objective of the study is to determine whether, in patients with symptomatic, advanced heart failure due to left ventricular systolic dysfunction, treatment with LCZ696 for 24 weeks will improve Pro-B-type Natriuretic Peptide (NT-proBNP) levels, which reflect hemodynamic and clinical status, compared to treatment with valsartan.
Eligibility Criteria
Inclusion Criteria
- Advanced HFrEF defined as including ALL
- LVEF≤ 35% documented during the preceding 12 months
- NYHA class IV symptomatology, defined as chronic dyspnea or fatigue at rest or on minimal exertion in the previous 3 months, or patients who require chronic inotropic therapy
- Minimum of 3 months GDMT for HF and/or intolerant to therapy
- Systolic blood pressure ≥ 90 mmHg
- Serum NT-proBNP ≥ 800 pg/mL OR BNP ≥ 250 pg/mL (most recent - less than 3 months old)
- Any one or more of the following objective findings of advanced HF including:
- Current inotropic therapy or use of inotropes in the past 6 months
- ≥ 1 hospitalization for heart failure in the past 6 months (not including the index hospitalization for inpatient participants)
- LVEF ≤ 25% (within the past 12 months)
- Peak VO2 5.5 mmol/L
- Severe liver dysfunction (Childs-Pugh Class C)
- Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
- Planned or recent (≤ 4 weeks) PCI, coronary artery bypass grafting, or biventricular pacing
- Currently hospitalized and listed status 1A, 1B or 1-4 for heart transplant
- Current or scheduled for LVAD implantation within 30 days of study enrollment
- Active infection (current use of oral or IV antimicrobial agents)
- Primary hypertrophic or infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
- Complex congenital heart disease
- Concomitant use of aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min/1.73 m²)
- Known pregnancy or anticipated pregnancy within the next 6 months or breastfeeding mothers
- Enrollment in any other investigational clinical trial within 30 days prior to screening
- Inability to comply with study procedures
Data sourced from ClinicalTrials.gov (NCT02816736). 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.