AzTrials
AzTrials

Heart Failure With Preserved Ejection Fraction (HFpEF)Phase 3PARAGLIDE-HFNCT03988634

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)

A Phase 3 study testing sacubitril/valsartan and valsartan in people with Heart Failure With Preserved Ejection Fraction (HFpEF), run by Novartis Pharmaceuticals at 97 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
sacubitril/valsartan and valsartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
467 participants
Where
97 sitesin 2 countries
Study dates
29 Jun 2019to 14 Dec 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent must be obtained prior to participation in the study
  • Patients >=18 years of age, male or female
  • Current hospitalization for Worsening Heart Failure (WHF) (HFpEF decompensation), or within 30 days of discharge following a WHF event (defined as hospitalization, emergency department (ED) visit or out-of-hospital urgent HF visit, all requiring IV diuretics). Patients with a diagnosis of acute heart failure had to have symptoms and signs of fluid overload (i.e. jugular venous distention, edema or rales on auscultation or pulmonary congestion on chest x-ray). Eligible patients were randomized after IV diuresis for HFpEF is given (and no earlier than 36 hours from their last ACEi dose if applicable) and within 30 days post-decompensation after presentation with acute HFpEF decompensation and meeting the following definitions of hemodynamic stability:
  • Randomized patients were hemodynamically stable defined in this study as:
  • SBP >=100mmHg for the preceding 6 hours prior to randomization; no symptomatic hypotension
  • No increase (intensification) in IV diuretic dose within last 6 hours prior to randomization
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  • No IV inotropic drugs for 24 hours prior to randomization
  • No IV vasodilators including nitrates within last 6 hours prior to randomization
  • HFpEF with most recent LVEF > 40% (within past 3 months)
  • Elevated NT-proBNP or BNP at the time of acute HFpEF decompensation or post-decompensation screening (and within 72 hours for out-of-hospital randomization, if applicable):
  • Patients not in Atrial Fibrillation(AF) at the time of biomarker assessment: NT-proBNP >= 500pg/mL or BNP >= 150 pg/mL; patients in AF at the time of biomarker assessment: NT-proBNP >= 1000pg/mL or BNP >= 300 pg/mL
  • Patients recruited in-hospital were randomized based on the qualifying local lab value in-hospital NT-proBNP or BNP value.
  • Patients enrolled post-decompensation can be randomized based on their NT-proBNP or BNP value in the following way:
  • if enrolling in post-decompensation setting then need eligible screening/local NTproBNP/BNP within 72 hours of randomization. The test value could be from recent hospitalization if within 72 hours or ii. would require (re)drawing NT-proBNP or BNP labs in post-decompensation setting if the lab value is not already available within the last 72 hours).
  • 6) Has not taken an ACEi for 36 hours prior to randomization

Who cannot join

  • Any clinical event within the 90 days prior to randomization that could have reduced the LVEF (i.e., myocardial infarction (MI), coronary artery bypass graft (CABG), unless an echo measurement was performed after the event confirming the LVEF to be > 40%
  • Entresto™ (sacubitril/valsartan) usage within the past 60 days
  • eGFR < 20ml/min/1.73 m2 as measured by the simplified Modification of Diet in Renal Disease (MDRD) formula at most recent assessment prior to randomization and within 24 hours prior to inpatient randomization or 72 hours prior to outpatient randomization
  • Serum potassium > 5.2 mEq/L at most recent assessment prior to randomization and within 24 hours prior to inpatient randomization or 72 hours prior to outpatient randomization
  • Acute coronary syndrome, stroke, transient ischemic attack; cardiac, carotid or other major CV surgery; percutaneous coronary intervention (PCI) or carotid angioplasty, within 30 days prior to randomization
  • Probable alternative diagnoses that in the opinion of the investigator could account for the patient's HF symptoms (i.e. dyspnea, fatigue) such as significant pulmonary disease (including primary pulmonary HTN), anemia or obesity.
Show all 22Show fewer
  • Isolated right HF in the absence of left-sided structural heart disease
  • History of hypersensitivity (i.e. including angioedema), known or suspected contraindications, or intolerance to any of the study drugs including ARNIs (i.e. sacubitril/valsartan), and/or ARBs
  • Patients with a known history of angioedema due to any etiology
  • Patients with a history of heart transplant or LVAD, currently on the transplant list, or with planned intent to implant LVAD or CRT device within the initial three months of enrollment during the trial
  • A cardiac or non-cardiac medical condition other than HF with an estimated life expectancy of < 6 months
  • Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy including suspected or confirmed amyloid heart disease (amyloidosis)
  • Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate > 110 bpm
  • Clinically significant congenital heart disease felt to be the cause of the patient's symptoms and signs of HF
  • Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the duration of the trial
  • Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
  • Known hepatic impairment (as evidenced by total bilirubin > 3 mg/dL, or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as varices
  • Participation in any other clinical trial involving investigational agents or devices within the past 30 days
  • Current confirmed COVID19 infection
  • Past COVID19 infection with persistent symptom burden suspected due to COVID19 (further defined in Section 5.2).
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug and for 7 days off of study drug. Highly effective contraception methods are defined in protocol.

Trial locations and contacts

97 sites in 2 countries.

97 sites in 2 countries

United States87 sites

  • Jefferson Abington .

    Abington, Pennsylvania, 19001

  • Albany Associates In Cardiology

    Albany, New York, 12205

  • Cedar Multi-Specialty Clinic

    Albuquerque, New Mexico, 87106

  • Alexandria Cardiology Clinic

    Alexandria, Louisiana, 71301

  • Pharma Tex Research .

    Amarillo, Texas, 79106

  • University of Michigan Hs

    Ann Arbor, Michigan, 48109

  • Morehouse School Of Medicine

    Atlanta, Georgia, 30310

  • Emory University School of Medicine/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University Cardiology Associates

    Augusta, Georgia, 30901

  • Johns Hopkins Univ School of Med

    Baltimore, Maryland, 21287

  • Northern Light Easter Maine Medical Center .

    Bangor, Maine, 04401

  • St John Health System

    Bartlesville, Oklahoma, 74006

  • The Franciscan Missionaries

    Baton Rouge, Louisiana, 70808

  • St Lukes Idaho Cardiology Associates CLCZ696BUS13

    Boise, Idaho, 83702

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston Univeristy Medical Center .

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med Ctr CLCZ696D2301

    Boston, Massachusetts, 02215

  • The University of Vermont Medical Center CRLX030A2301

    Burlington, Vermont, 05401

  • University Of North Carolina At Chapel Hill CRLX030A2209

    Chapel Hill, North Carolina, 27599-7075

  • University of Chicago .

    Chicago, Illinois, 60637

  • Cleveland Clinic Foundation .

    Cleveland, Ohio, 44195

  • St Francis Medical Center

    Colorado Springs, Colorado, 80923

  • Baylor University Medical Center .

    Dallas, Texas, 75246

  • Detroit Medical Center Cardiovascular Clinical Trial .

    Detroit, Michigan, 48201

  • Henry Ford Hospital Cardiovascular Medicine

    Detroit, Michigan, 48202

  • Duke Health

    Durham, North Carolina, 27710

  • Amita Health

    Elk Grove Village, Illinois, 60007

  • Midwest Cardiovascular Research and Education Foundation .

    Elkhart, Indiana, 46514

  • Inspira Health Network

    Elmer, New Jersey, 08318

  • New York Presbyterian Queens .

    Flushing, New York, 11355

  • University of Florida Health .

    Gainesville, Florida, 32610

  • The University of Texas Medical Branch

    Galveston, Texas, 77555-1062

  • Cooper University Health Care

    Haddon Heights, New Jersey, 08035

  • New Generation of Medical Research Avera Health N Central Heart

    Hialeah, Florida, 33016

  • Indiana University Health

    Indianapolis, Indiana, 46202

  • Franciscan Health Services Research Center .

    Indianapolis, Indiana, 46237

  • University of Calif Irvine Med Cntr

    Irvine, California, 92660

  • Jackson Heart Clinic

    Jackson, Mississippi, 39216

  • University of Florida Health Science Center

    Jacksonville, Florida, 32209

  • United Health Services Office Of Clinical Trails CLCZ696BUS01

    Johnson, New York, 13790

  • The Uni of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Colorado Heart and Vascular .

    Lakewood, Colorado, 80228

  • Univ Medical Center Las Vegas

    Las Vegas, Nevada, 89201

  • Nebraska Heart Institute CHI Health Nebraska

    Lincoln, Nebraska, 68510

  • South Denver Cardiology Associates PC

    Littleton, Colorado, 80120

  • Memorial Care Health System Memorialcare Long Beach

    Long Beach, California, 90806

  • University Of Southern California .

    Los Angeles, California, 90033-4605

  • University Of Southern California

    Los Angeles, California, 90033-4605

  • Centra Health

    Lynchburg, Virginia, 24501

  • University of Wisconsin School of Medicine and Public Health CLCZ696BUS01

    Madison, Wisconsin, 53792-1615

  • Northwell Health .

    Manhasset, New York, 11030

  • Indiana University Health

    Muncie, Indiana, 47303

  • VA Tennessee Valley Healthcare System

    Nashville, Tennessee, 37212

  • Allegheny Valley Hospital .

    Natrona Heights, Pennsylvania, 15065

  • Mount Sinai Hospital .

    New York, New York, 10029

  • Cardiology Physicians PA .

    Newark, Delaware, 19713

  • Saint Michael Medical Center

    Newark, New Jersey, 07102

  • Capital Area Research LLC CACZ885M2301

    Newport, Pennsylvania, 17074

  • Midwest Cardiovascular Institute .

    Oakbrook Terrace, Illinois, 60181

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Advocate Medical Group .

    Park Ridge, Illinois, 60068

  • Unity Point Health Methodist

    Peoria, Illinois, 61606

  • OSF HealthCare

    Peoria, Illinois, 61614

  • Thomas Jefferson Univ Hospital .

    Philadelphia, Pennsylvania, 19107

  • HealthQuest

    Poughkeepsie, New York, 12601

  • Regional Health Clinic Research .

    Rapid City, South Dakota, 57701

  • R Ins For Heart And Vascular Health

    Reno, Nevada, 89502

  • Reid Hosp And Hlth Care Services

    Richmond, Indiana, 47374

  • Catholic Hlth Svcs of Long Island

    Roslyn, New York, 11576

  • Novartis Investigative Site

    Saint Paul, Minnesota, 55101

  • Tidal Health Peninsula Regional Inc .

    Salisbury, Maryland, 21804

  • San Diego Cardiac Center

    San Diego, California, 92123

  • Zuckerberg General W84 Research .

    San Francisco, California, 94110

  • Sutter Health Network .

    San Pablo, California, 94806

  • Helping Hands Medical Associates INC

    Santa Ana, California, 92704

  • Intercoastal Medical Group

    Sarasota, Florida, 34239

  • Swedish Medical Ctr Cardiovascular Re

    Seattle, Washington, 98122

  • North Central Heart .

    Sioux Falls, South Dakota, 57105

  • Mount Sinai Health System

    Staten Island, New York, 10310

  • Stony Brook University Medical Center CLCZ696G2301

    Stony Brook, New York, 11794

  • Montefiore Medical Center .

    The Bronx, New York, 10461

  • St. Vincent Mercy Medical Center

    Toledo, Ohio, 43608

  • Regional Medical Labaratory

    Tulsa, Oklahoma, 74104

  • Hartford Healthcare Headache Center

    West Hartford, Connecticut, 06109

  • VA Connecticut Healthcare System

    West Haven, Connecticut, 06516

  • Northwestern Medicine Northwestern University

    Winfield, Illinois, 60190

  • Trinity Health Michigan Heart .

    Ypsilanti, Michigan, 48197

Other trials in United States

Canada10 sites

  • Novartis Investigative Site

    Hamilton, Ontario, L8L 2X2

  • Novartis Investigative Site

    Montreal, Quebec, H1T 1C8

  • Novartis Investigative Site

    Montreal, Quebec, H2X 0A9

  • Novartis Investigative Site

    Montreal, Quebec, H3G 1A4

  • Novartis Investigative Site

    Québec, Quebec, G1R 2J6

  • Novartis Investigative Site

    Saguenay, Quebec, G7H 5H6

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    Terrebonne, Quebec, J6V 2H2

  • Novartis Investigative Site

    Victoria, British Columbia, V8R4R2

  • Novartis Investigative Site

    Winnipeg, Manitoba, R2H 2A6

Other trials in Canada

About this study

Official title: A Multicenter, Randomized, Double-blind, Double Dummy, Parallel Group, Active-controlled Study to Evaluate the Effect of Sacubitril/Valsartan (LCZ696) Versus Valsartan on 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)

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.

Read the detailed description

This study used a randomized, double-blind, double-dummy, active-controlled, parallel group design conducted across 100 centers in the US and Canada. The study duration was a maximum of 20 months (minimum follow up was 8 weeks).

Randomized patients were deemed hemodynamically stabilized and needed to meet all inclusion and none of the exclusion criteria. Patients were randomized 1:1 to LCZ696 or valsartan. Initial dose at randomization was determined based on the patient's previous dose of or lack of ACEi/angiotensin receptor blocker (ARB) immediately prior to current worsening heart failure (WHF) event (heart failure with preserved ejection fraction [HFpEF]) decompensation, or at the time of post-decompensation randomization.

LCZ696 dose or valsartan dose levels may have been increased to the targeted desired dose of 97/103 mg [200 mg] BID or valsartan 160 mg BID on an every 2-week basis or earlier based on clinical need and investigator judgment. Every effort was made to titrate to and maintain patients on the target dose level, as tolerated by the patient.

To maintain the blinding, patients were required to take their assigned active treatment tablet along with placebo matching the opposite treatment BID.

The protocol had 4 amendments. Protocol Version 00 (Original Protocol) included a double-blind phase through Week 8 followed by an open-label phase during Weeks 8 to 12. Protocol Amendment 01 omitted the open-label phase and followed patients for a maximum of 20 months in a double-blinded treatment phase. Throughout all protocol versions, the primary endpoint remained the time-averaged proportional change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from Baseline to Weeks 4 and 8. The most recent protocol amendment (Amendment 04) reduced the sample size to approximately 450 patients (from 800) with 85% power for the primary endpoint, deemphasizing the statistical power for key secondary clinical endpoints; however, clinical events were still assessed as secondary endpoints.

No efficacy analyses include "OPEN LABEL' data. After Protocol Amendment 01, the open-label option was removed from the study, only the 233 patients randomized in the Double-blind Phase Sacubitril+ Valsartan (LCZ696) and the 233 patients randomized in the Double-blind Phase Valsartan arms were included in the efficacy analysis.

Being tested
sacubitril/valsartan, valsartan, sacubitril/valsartan matching placebo, valsartan matching placebo
Keywords
Heart failure with preserved ejection fraction (HFpEF), Heart failure hospitalization, NYHA, NT-proBNP, Acute decompensated heart failure, Sacubitril/valsartan, Global evaluation of treatment effectiveness (GETE), Worsening Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sacubitril/valsartanDrug

    Also called LCZ696

    Sacubitril/valsartan (LCZ696) was available as 24/26 mg, 49/51 mg, and 97/103 mg in tablet form to be taken orally, twice daily

  • valsartanDrug

    Valsartan was available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily

  • sacubitril/valsartan matching placeboDrug

    Sacubitril/valsartan (LCZ696) matching placebo was available as tablet form to be taken orally, twice daily

  • valsartan matching placeboDrug

    Valsartan matching placebo was available as tablet form to be taken orally, twice daily

Study groups in NCT03988634
Study groupRoleWhat they receive
sacubitril/valsartan (LCZ696)ExperimentalStudy treatment was titrated to the target dose of sacubitril/valsartan (LCZ696) 97/103 mg twice daily (Dose Level 3). Patients were required to take a total of two tablets twice daily (one tablet of active sacubitril and valsartan , and one tablet of valsartan matching placebo)
Receives: Drug: sacubitril/valsartan; Drug: valsartan matching placebo
valsartanActive comparatorStudy treatment was titrated to the target dose of valsartan 160 mg twice daily (Dose Level 3). Patients were required to take a total of two tablets twice daily (one tablet of active valsartan, and one tablet of sacubitril and valsartan matching placebo)
Receives: Drug: valsartan; Drug: sacubitril/valsartan matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time-averaged Proportional Change in NT proBNP From Baseline to Weeks 4 and 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: Week - 8/Baseline.

    NT-proBNP is a protein produced in large amounts by the heart when it is not working properly, as in heart failure.

    Baseline value was the last non-missing assessment of plasma NT-proBNP before the first administration of study drug.

    Measured: Baseline, Average of Week 4 and Week 8

Secondary outcomes (7)

  1. Number of Pairwise Comparisons With Wins or Ties in the Endpoint Adjudication Committee (EAC)-Adjudicated Composite Hierarchical Outcome

    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) or a 'loser'. Otherwise they are considered tied. The reported unit is the total "wins" or "ties" for each treatment group from performing such a hierarchical comparison.

    Measured: Up to 84 weeks

  2. EAC Adjudicated Recurrent Composite Events

    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 criteria and processes.

    Events that occurred in the double-blind treatment phase are included in the analysis.

    Measured: Up to Week 84

  3. Total Number of Confirmed Incidences of a Composite Endpoint of Worsening Renal Function

    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 treatment phase were included in the analysis.

    Measured: Up to Week 84

  4. Proportional Change in NT-proBNP From Baseline to 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.

    Measured: Baseline and Week 8

  5. Proportional Change From Baseline in Hs-Troponin at Weeks 4 and 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.

    Measured: Baseline, Week 4 and Week 8

  6. Dosing Levels and Discontinuations

    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

    Measured: Randomization, Week 8, Week 24

  7. Incidence of Adverse Events of Special Interest (AESI) During Treatment

    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%)

    Measured: Up to week 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2019
  2. Study start29 Jun 2019
  3. Primary completion14 Dec 2022
  4. Study completion14 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
467 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03988634
Sponsor's protocol ID
CLCZ696DUS01
Acronym
PARAGLIDE-HF
Status last verified
Mar 2025
First submitted
13 Jun 2019
Last updated
6 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of the patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Peters AE, Li S, Cyr D, Williamson KM, Zieroth S, Fudim M, Ward JH, Mentz RJ. Influence of ejection fraction on outcomes with sacubitril/valsartan in patients with worsening heart failure with EF>40%: The PARAGLIDE-HF Trial. Am Heart J. 2025 Nov;289:158-167. doi: 10.1016/j.ahj.2025.04.023. Epub 2025 Apr 21.

    PubMed 40268180

  • Rambarat P, Erickson T, Cyr D, Ward J, Hernandez A, Morrow D, Starling R, Velazquez E, Zieroth S, Williamson K, Solomon S, Mentz R. Effects of angiotensin-neprilysin inhibition in women vs men: Insights from PARAGLIDE-HF. Am Heart J. 2025 Oct;288:41-51. doi: 10.1016/j.ahj.2025.03.017. Epub 2025 Mar 31.

    PubMed 40174692

  • Shoji S, Cyr DD, Hernandez AF, Velazquez EJ, Ward JH, Williamson KM, Sarwat S, Starling RC, Desai AS, Zieroth S, Solomon SD, Mentz RJ. Win Ratio Analyses Using a Modified Hierarchical Composite Outcome: Insights From PARAGLIDE-HF. Am Heart J. 2025 Feb;280:70-78. doi: 10.1016/j.ahj.2024.10.020. Epub 2024 Nov 4.

    PubMed 39505123

  • Fudim M, Cyr DD, Ward JH, Hernandez AF, Lepage S, Morrow DA, Sharma K, Claggett BL, Starling RC, Velazquez EJ, Williamson KM, Desai AS, Zieroth S, Solomon SD, Braunwald E, Mentz RJ; PARAGLIDE-HF investigators. Association of Sacubitril/Valsartan vs Valsartan With Blood Pressure Changes and Symptomatic Hypotension: the PARAGLIDE-HF Trial. J Card Fail. 2024 Dec;30(12):1568-1577. doi: 10.1016/j.cardfail.2024.04.030. Epub 2024 May 26.

    PubMed 38802053

  • Morrow DA, Velazquez EJ, Desai AS, DeVore AD, Lepage S, Park JG, Sharma K, Solomon SD, Starling RC, Ward JH, Williamson KM, Zieroth S, Hernandez AF, Mentz RJ, Braunwald E. Sacubitril/Valsartan in Patients Hospitalized With Decompensated Heart Failure. J Am Coll Cardiol. 2024 Mar 26;83(12):1123-1132. doi: 10.1016/j.jacc.2024.01.027.

    PubMed 38508844

  • Mentz RJ, Ward JH, Hernandez AF, Lepage S, Morrow DA, Sarwat S, Sharma K, Starling RC, Velazquez EJ, Williamson KM, Desai AS, Zieroth S, Solomon SD, Braunwald E; PARAGLIDE-HF Investigators. Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure. J Am Coll Cardiol. 2023 Jul 4;82(1):1-12. doi: 10.1016/j.jacc.2023.04.019. Epub 2023 May 21.

    PubMed 37212758

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing sacubitril/valsartan and valsartan in people with Heart Failure With Preserved Ejection Fraction (HFpEF), run by Novartis Pharmaceuticals at 97 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 97 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time-averaged Proportional Change in NT proBNP From Baseline to Weeks 4 and 8 (time frame: Baseline, Average of Week 4 and Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03988634, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.

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