Adults 18 to 85, any sex, with Heart Failure. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Change in NT-proBNPPrimary· Baseline, 2, 4, 8, 12, and 24 weeks
The proportional change from baseline in the AUC for NT-proBNP levels measured at 2, 4, 8, 12, and 24 weeks. AUC was normalized for time and divided by the baseline value of NTproBNP so it has no unitshas no units. With the log-scale, the value of 0 indicates, on average, no change in NTproBNP from baseline. A value \> 0 indicates an increase in log NT Pro BNP relative to baseline and a value \< 0 indicates a decrease in log NT Pro BNP relative to baseline.
Group
Value
95% CI
LCZ696 (Entresto) + Placebo
0.14
± 0.65
Valsartan + Placebo
0.19
± 0.50
Composite Endpoint of the Effects of LCZ696 (Number of Days)Secondary· Randomization through 24 weeks
Composite endpoint of effects of LCZ696 compared to valsartan over 24 weeks will be compared based upon the number of days subjects are
* alive and out of hospital
* not listed for transplant (Status 1A, 1B or 1-4), or undergoing transplant
* not implanted with an LVAD
* not maintained or started on continuous inotropic therapy for ≥ 7 days
* not hospitalized twice for HF (following the index admission) The days alive and out of hospital will end on the day of the second HF readmission, if applicable.
Group
Value
95% CI
LCZ696 (Entresto) + Placebo
108.58
95.22 – 121.95
Valsartan + Placebo
119.8
107.64 – 131.96
Tolerability - Target DoseSecondary· Randomization through 24 weeks
Tolerability as measured by number of subjects achieving a target dose of 0% (stopped study drug early or was never started on study drug), 25%, 50% or 100% of valsartan or LCZ696 (based on last dose of study drug taken prior to end of study)
Group
Value
95% CI
LCZ696 (Entresto) + Placebo
49
Valsartan + Placebo
37
LCZ696 (Entresto) + Placebo
28
Valsartan + Placebo
41
LCZ696 (Entresto) + Placebo
33
Valsartan + Placebo
30
LCZ696 (Entresto) + Placebo
57
Valsartan + Placebo
60
Tolerability - HypotensionSecondary· Randomization through 24 weeks
Tolerability as measured by number of subjects developing hypotension (SBP ≤ 85 mmHg) with symptoms
Group
Value
95% CI
LCZ696 (Entresto) + Placebo
29
Valsartan + Placebo
20
LCZ696 (Entresto) + Placebo
138
Valsartan + Placebo
148
Tolerability - Renal FunctionSecondary· Randomization through 24 weeks
Tolerability as measured by number of subjects developing worsening renal function (eGFR \< 20 ml/min/1.73 m²)
Group
Value
95% CI
LCZ696 (Entresto) + Placebo
7
Valsartan + Placebo
7
LCZ696 (Entresto) + Placebo
160
Valsartan + Placebo
161
Tolerability - HyperkalemiaSecondary· Randomization through 24 weeks
Tolerability as measured by number of subjects developing moderate (\>/= 5.5 mmol/L-5.9 mmol/L) or severe (\>/= 6 mmol/L) hyperkalemia
Group
Value
95% CI
LCZ696 (Entresto) + Placebo
28
Valsartan + Placebo
15
LCZ696 (Entresto) + Placebo
139
Valsartan + Placebo
153
Adverse events — posted to ClinicalTrials.gov
Time frame: Randomization to week 24.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
LCZ696 (Entresto) + Placebo
Serious: 43/167 (26%)
Deaths: 13/167
Valsartan + Placebo
Serious: 27/168 (16%)
Deaths: 8/168
Serious adverse events (89 terms)
Reaction
System
LCZ696 (Entresto) + Placebo
Valsartan + Placebo
Multiple Organ Dysfunction Syndrome
General disorders
—
—
Pneumonia
Infections and infestations
—
—
Urinary Tract Obstruction
Renal and urinary disorders
—
—
Respiratory Failure
Respiratory, thoracic and mediastinal disorders
—
—
Coagulopathy
Blood and lymphatic system disorders
—
—
Gastrointestinal Haemorrhage
Gastrointestinal disorders
—
—
Pyrexia
General disorders
—
—
Sepsis
Infections and infestations
—
—
Septic Shock
Infections and infestations
—
—
Dehydration
Metabolism and nutrition disorders
—
—
Hyperglycaemia
Metabolism and nutrition disorders
—
—
Hypokalaemia
Metabolism and nutrition disorders
—
—
Adenocarcinoma of Colon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT04164732 — Study of Efficacy of Oral Sacubitril/Valsartan in Adult Patients With Non-obstructive Hypertrophic Cardiomyopathy
· Phase 2
· completed
NCT03872778 — [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-neoB Lesion Uptake
· Phase 1, PHASE2
· completed
NCT03909295 — An Open-label Extension Study Evaluating Safety and Tolerability of LCZ696 in Subjects Who Completed PARAGON-HF in Japan
· Phase 3
· terminated
NCT03917459 — COmparing arNi and Ace For Improving Erectile Dysfunction in mEN With reduCed Ejection Fraction Heart Failure
· Phase 3
· completed
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Duke University
Last refreshed: 3 December 2021
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02816736.