Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event (HFpEF Decompensation) Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation (PARAGLIDE-HF)
CompletedPhase 3Results postedLast updated 6 March 2025
What this trial tests
Phase 3 trial testing sacubitril/valsartan in Heart Failure With Preserved Ejection Fraction (HFpEF) in 467 participants. Completed in 14 December 2022.
Adults 18 to 99, any sex, with Heart Failure With Preserved Ejection Fraction (HFpEF). 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.
Time-averaged Proportional Change in NT proBNP From Baseline to Weeks 4 and 8Primary· Baseline, Average of Week 4 and Week 8
To demonstrate the effect of sacubitril/valsartan vs. valsartan on time-averaged proportional change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to weeks 4 and 8 in heart failure with preserved ejection fraction (HFpEF) patients with a worsening heart failure event (HFpEF decompensation) who have been stabilized for and initiated at the time of or within 30 days post-decompensation.
Plasma NT-proBNP (pg/mL) values were averaged from Week 4 and Week 8 visits. The change from baseline to average of Week 4 and Week 8 was expressed as the geometric mean of the ratio: Wee
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
0.7200
0.6430 – 0.8062
Valsartan
0.8425
0.7561 – 0.9387
Number of Pairwise Comparisons With Wins or Ties in the Endpoint Adjudication Committee (EAC)-Adjudicated Composite Hierarchical OutcomeSecondary· Up to 84 weeks
This hierarchical composite endpoint consists of 4 ordered components: 1. Time to CV death, 2. Number and times of HF hospitalizations during follow-up, 3. Number and times of urgent HF visits during follow-up, 4. Time averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8. This endpoint was analyzed estimating the unmatched win ratio by comparing every participant in the sacubitril/valsartan arm to every participant in the valsartan arm to determine a winner (unmatched pairing method). For every pair, a patient is labelled a 'winner' (i.e. achieve a better clinical outcome)
Time to CV death wins
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
2170
Valsartan
1536
Time to CV death ties
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
50583
Valsartan
50583
Number and times of HF hospitalizations during follow-up wins
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
6963
Valsartan
6357
Number and times of HF hospitalizations during follow-up ties
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
37263
Valsartan
37263
Number and times of urgent HF visits during follow-up wins
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
930
Valsartan
572
Number and times of urgent HF visits during follow-up ties
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
35761
Valsartan
35761
Time-averaged proportional change in NT-proBNP wins
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
9987
Valsartan
8343
Time-averaged proportional change in NT-proBNP ties
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
17431
Valsartan
17431
EAC Adjudicated Recurrent Composite EventsSecondary· Up to Week 84
This endpoint calculated the cumulative number of the following composite events over time:
* CV death
* recurrent HF hospitalizations
* recurrent urgent HF visits The time to these recurrent events was analyzed using the semi-parametric proportional rates model (abbreviated as LWYY model).
The exposure-adjusted rate per 100 subject years (EAR) was calculated diving the total number of events by 100 subject years (total exposure up to event/censoring).
The role of the Endpoint Adjudication Committee (EAC) was to ensure that all treatment outcomes were judged uniformly, using standard criter
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
63.519
51.330 – 77.732
Valsartan
76.189
63.010 – 91.310
Total Number of Confirmed Incidences of a Composite Endpoint of Worsening Renal FunctionSecondary· Up to Week 84
This endpoint calculated the incidences of a composite endpoint of worsening renal function defined as:
* renal death (from adverse events data)
* reaching end-stage renal disease (ESRD) (Sustained eGFR \<15mL/min/m2, chronic dialysis, or renal transplant)
* ≥ 50% decline in estimated glomerular filtration rate (eGFR) relative to baseline \[using central laboratory measurements (scheduled or unscheduled visits)\]
The Investigator-reported AE and central laboratory data was used to identified event of interest in this secondary endpoint.
Events that occurred in the randomized double-blind tr
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
34
Valsartan
46
Proportional Change in NT-proBNP From Baseline to Week 8Secondary· Baseline and Week 8
This endpoint intended to assess the effect of sacubitril/valsartan vs. valsartan on change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to Week 8.
NT-proBNP is a protein produced in large amounts by the heart when it is not working properly, as in heart failure.
The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
0.6778
0.5882 – 0.7810
Valsartan
0.7275
0.6359 – 0.8323
Proportional Change From Baseline in Hs-Troponin at Weeks 4 and 8Secondary· Baseline, Week 4 and Week 8
This endpoint intended to assess the effect of sacubitril/valsartan vs. valsartan on change from baseline in high sensitivity (hs)-Troponin at Weeks 4 and 8. Analysis was repeated for both the visits, Week 4 and Week 8 separately.
Hs-Troponin-T is a biomarker that is released from the heart under stress or injury conditions.
The change from baseline to Week 4 and Week 8 was expressed as the geometric mean of the ratio: Week 4 or Week 8/Baseline.
Week 4
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
0.8124
0.76 – 0.87
Valsartan
0.9826
0.92 – 1.05
Week 8
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
0.7545
0.70 – 0.81
Valsartan
0.9310
0.87 – 1.00
Dosing Levels and DiscontinuationsSecondary· Randomization, Week 8, Week 24
The dosing level has been summarized by treatment group and in-/out-of-hospital randomization status. The dose levels used were:
Dose Level 1: 40 mg valsartan or 24/26 mg \[50 mg\] LCZ696, BID; Dose Level 2: 80 mg valsartan or 49/51 mg \[100 mg\] LCZ696, BID; Dose Level 3: 160 mg valsartan or 97/103 mg \[200 mg\] LCZ696, BID
Patients counted as "Off Treatment" are those who prematurely permanently discontinued study treatment but continued with visits.
Patients counted as "No Treatment" are those who permanently discontinued with both study treatment and study visits
Incidence of Adverse Events of Special Interest (AESI) During TreatmentSecondary· Up to week 84
This endpoint intended to calculate the incidence of the following adverse events of special interest (AESI) during treatment:
Symptomatic hypotension, Hyperkalemia (potassium \> 5.5 mEq/L), Angioedema and worsening renal function (defined as an increase in serum creatinine of ≥ 0.5 mg/dL and worsening of the eGFR by at least 25%)
Symptomatic hypotension
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
56
Valsartan
36
Hyperkalemia
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
45
Valsartan
43
Angioedema
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
0
Valsartan
1
Worsening renal function
Group
Value
95% CI
Sacubitril/Valsartan (LCZ696)
50
Valsartan
72
Adverse events — posted to ClinicalTrials.gov
Time frame: Adverse events of the double-blind phase were reported from first dose of study treatment until end of study treatment plus 1 month post treatment, up to a maximum duration of 21 months. For those patients enrolled during the original version (00) of the protocol, where the open-label phase existed, adverse events were reported during the 4 week Open-Label period, and 1 month post treatment, for a maximum of 2 months..
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
The effect of sacubitril/valsartan vs. valsartan on changes in NT-proBNP, safety, and tolerability in HFpEF patients with a WHF event (HFpEF decompensation) who had been stabilized and initiated at the time of or within 30 days post-decompensation.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT06149104 — A Safety Study of Sacubitril/Valsartan in Japanese Pediatric Patients With Heart Failure Due to Systemic Left Ventricle
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· completed
NCT05870709 — Real World, Pharmacy-assessed Adherence to New Onset Entresto® (Sacubitril/Valsartan) in Patients With Chronic Heart Fai
· withdrawn
NCT07498335 — Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary
· Phase 3
· not yet recruiting
NCT07489573 — Study of Efficacy and Safety of Secukinumab in Chinese Adult Patients With Moderate to Severe Hidradenitis Suppurativa
· Phase 4
· not yet recruiting
NCT07484269 — PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan
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NCT07416162 — A Study of Iptacopan in Korean Patients With Paroxysmal Nocturnal Hemoglobinuria or C3 Glomerulopathy
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NCT07387926 — Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+
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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 Novartis Pharmaceuticals
Last refreshed: 6 March 2025
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/NCT03988634.