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.
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
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction (HFpEF)
- 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
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.
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- 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
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
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 group | Role | What they receive |
|---|---|---|
| sacubitril/valsartan (LCZ696) | Experimental | Study 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 |
| valsartan | Active comparator | Study 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.
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)
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
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
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
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
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
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
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.
- First posted17 Jun 2019
- Study start29 Jun 2019
- Primary completion14 Dec 2022
- Study completion14 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Preserved Ejection Fraction (HFpEF)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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 40268180Rambarat 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 40174692Shoji 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 39505123Fudim 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 38802053Morrow 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 38508844Mentz 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