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NCT01920711: PARAGON-HF

Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction

Completed Phase 3 Results posted Last updated 29 September 2020
What this trial tests

Phase 3 trial testing LCZ696 in Heart Failure With Preserved Ejection Fraction in 4,822 participants. Completed in 7 June 2019.

Timeline
18 July 2014
Primary endpoint
7 June 2019
7 June 2019

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment4,822
Start date18 July 2014
Primary completion7 June 2019
Estimated completion7 June 2019
Sites715 locations across Italy, Colombia, Finland, Japan, Taiwan, Poland, South Korea, Philippines

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

50 and older, any sex, with Heart Failure With Preserved Ejection Fraction. 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.

Cumulative Number of Primary Composite Events of Cardiovascular (CV) Death and Total (First and Recurrent) HF Hospitalizations. Primary · Total follow up time (up to 57 months)

The primary objective of this study is to compare LCZ696 to valsartan in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF hospitalizations, in HF patients (New York Heart Association \[NYHA\] Class II-IV) with preserved ejection fraction (left ventricular ejection fraction \[LVEF\] ≥45%). The treatment arm with the lower rate of events will be deemed as having a successful response.

Primary Composite Events
GroupValue95% CI
LCZ696894
Valsartan1009
Total Hospitalizations for heart failure
GroupValue95% CI
LCZ696690
Valsartan797
Cardiovascular death
GroupValue95% CI
LCZ696204
Valsartan212
Change in the Clinical Summary Score From Baseline to Month 8 by Kansas City Cardiomyopathy Questionnaire (KCCQ) Secondary · Baseline, 8 months

The KCCQ is a validated instrument for self-assessment of quality of life and health status in heart failure (HF) patients. The clinical summary score, which is derived from the physical limitations and heart failure (HF) symptoms domains of the KCCQ is a valid measure for assessing the patient's health aspects that may be influenced by CV medications. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. Evaluation of change from baseline to month 8 in KCCQ a most sensitive, specific, and responsive health-related quality of life measure for heart fa

GroupValue95% CI
LCZ696-1.5073± 0.3709
Valsartan-2.5338± 0.3729
Change From Baseline to Month 8 in New York Heart Association (NYHA) Functional Class Secondary · Baseline, 8 months

Evaluation of change from baseline to Month 8 in NYHA functional class, a well established grading scale used to classify a heart failure's (HF) patients' level of functionality based on the signs and symptoms of HF exhibited by the patient.

Improved (n=2316, 2302)
GroupValue95% CI
LCZ696347
Valsartan289
Unchanged (n=2316, 2302)
GroupValue95% CI
LCZ6961767
Valsartan1792
Worsened (n=2316, 2302)
GroupValue95% CI
LCZ696202
Valsartan221
Participants With First Occurrence of a Composite Renal Endpoint Secondary · Randomization to total follow-up time (up to 57 months)

Analyis of composite renal endpoint defined as renal death, or reaching ESRD, or ≥50% decline in eGFR relative to baseline, using Cox's proportional hazards model.

Composite renal endpoint
GroupValue95% CI
LCZ69633
Valsartan64
Renal Death
GroupValue95% CI
LCZ6961
Valsartan1
Reaching ESRD
GroupValue95% CI
LCZ6967
Valsartan12
>=50% decline in eGFR from baseline
GroupValue95% CI
LCZ69627
Valsartan60
All-cause Mortality Secondary · Randomization to total follow up time (up to 57 months)

Analysis for all-cause mortality using Cox's proportional hazards model.

GroupValue95% CI
LCZ696342
Valsartan349

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approx. 5 years.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LCZ696
Serious: 1424/2419 (59%)
Deaths: 347/2419
Valsartan
Serious: 1416/2402 (59%)
Deaths: 357/2402
All Patients
Serious: 2840/4821 (59%)
Deaths: 704/4821

Serious adverse events (1274 terms)

ReactionSystemLCZ696ValsartanAll Patients
Cardiac failureCardiac disorders
PneumoniaInfections and infestations
Atrial fibrillationCardiac disorders
Acute kidney injuryRenal and urinary disorders
Cardiac failure congestiveCardiac disorders
Cardiac failure acuteCardiac disorders
AnaemiaBlood and lymphatic system disorders
Urinary tract infectionInfections and infestations
Acute myocardial infarctionCardiac disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
SyncopeNervous system disorders
Angina unstableCardiac disorders
Angina pectorisCardiac disorders
Cerebrovascular accidentNervous system disorders
Non-cardiac chest painGeneral disorders
BronchitisInfections and infestations
Renal impairmentRenal and urinary disorders
SepsisInfections and infestations
Myocardial infarctionCardiac disorders
Gastrointestinal haemorrhageGastrointestinal disorders
HyperkalaemiaMetabolism and nutrition disorders
Ischaemic strokeNervous system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (59 terms — click to expand)

ReactionSystemLCZ696ValsartanAll Patients
HypotensionVascular disorders
Renal impairmentRenal and urinary disorders
HypertensionVascular disorders
HyperkalaemiaMetabolism and nutrition disorders
Urinary tract infectionInfections and infestations
Cardiac failureCardiac disorders
Atrial fibrillationCardiac disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
NasopharyngitisInfections and infestations
AnaemiaBlood and lymphatic system disorders
BronchitisInfections and infestations
DiarrhoeaGastrointestinal disorders
Oedema peripheralGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
InfluenzaInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
FatigueGeneral disorders
PneumoniaInfections and infestations
FallInjury, poisoning and procedural complications
Renal failureRenal and urinary disorders
Non-cardiac chest painGeneral disorders
ConstipationGastrointestinal disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Glomerular filtration rate decreasedInvestigations
Angina pectorisCardiac disorders
GoutMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
CataractEye disorders
Weight decreasedInvestigations
HaematuriaRenal and urinary disorders
BradycardiaCardiac disorders
DepressionPsychiatric disorders
VertigoEar and labyrinth disorders
HyperuricaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Cardiac failure, Pneumonia, Atrial fibrillation, Acute kidney injury, Cardiac failure congestive, Cardiac failure acute, Anaemia, Urinary tract infection.

Data from ClinicalTrials.gov NCT01920711 adverse events section.

Sponsor's own description

The purpose of this study was to evaluate the effect of LCZ696 compared to valsartan in the reduction of cardiovascular death and heart failure(HF) hospitalizations in patients with HF with preserved ejection fraction.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.
    Solomon SD, McMurray JJV, Anand IS, Ge J, et al · · 2019 · cited 1743× · PMID 31475794 · DOI 10.1056/nejmoa1908655
  2. Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure.
    Solomon SD, Vaduganathan M, L Claggett B, Packer M, et al · · 2020 · cited 382× · PMID 31736342 · DOI 10.1161/circulationaha.119.044586
  3. Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.
    McMurray JJV, Jackson AM, Lam CSP, Redfield MM, et al · · 2020 · cited 292× · PMID 31736337 · DOI 10.1161/circulationaha.119.044491
  4. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease.
    Lee DI, Zhu G, Sasaki T, Cho GS, et al · · 2015 · cited 281× · PMID 25799991 · DOI 10.1038/nature14332
  5. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes.
    Senni M, Paulus WJ, Gavazzi A, Fraser AG, et al · · 2014 · cited 262× · PMID 25104786 · DOI 10.1093/eurheartj/ehu204
  6. Arterial Stiffening With Exercise in Patients With Heart Failure and Preserved Ejection Fraction.
    Reddy YNV, Andersen MJ, Obokata M, Koepp KE, et al · · 2017 · cited 214× · PMID 28683960 · DOI 10.1016/j.jacc.2017.05.029
  7. Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction: Rationale and Design of the PARAGON-HF Trial.
    Solomon SD, Rizkala AR, Gong J, Wang W, et al · · 2017 · cited 208× · PMID 28662936 · DOI 10.1016/j.jchf.2017.04.013
  8. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment.
    Volpe M, Carnovali M, Mastromarino V. · · 2016 · cited 180× · PMID 26637405 · DOI 10.1042/cs20150469

Verify or expand the search:

Other trials of LCZ696

Trials testing the same drug.

Other recruiting trials for Heart Failure With Preserved Ejection Fraction

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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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/NCT01920711.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing