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) (PARAGLIDE-HF)

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
• Intervention / Treatment: Drug: sacubitril/valsartan; Drug: valsartan matching placebo; Drug: valsartan; Drug: sacubitril/valsartan matching placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 467
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • Novartis Investigative Site
  • British Columbia
    • Victoria, British Columbia, Canada, V8R4R2
      • Novartis Investigative Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Novartis Investigative Site
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3G 1A4
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2X 0A9
      • Novartis Investigative Site
    • Saguenay, Quebec, Canada, G7H 5H6
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Novartis Investigative Site
    • Terrebonne, Quebec, Canada, J6V 2H2
      • Novartis Investigative Site
• United States
  • California
    • Irvine, California, United States, 92660
      • University of Calif Irvine Med Cntr
    • Long Beach, California, United States, 90806
      • Memorial Care Health System Memorialcare Long Beach
    • Los Angeles, California, United States, 90033-4605
      • University Of Southern California .
    • Los Angeles, California, United States, 90033-4605
      • University of Southern California
    • San Diego, California, United States, 92123
      • San Diego Cardiac Center
    • San Francisco, California, United States, 94110
      • Zuckerberg General W84 Research .
    • San Pablo, California, United States, 94806
      • Sutter Health Network .
    • Santa Ana, California, United States, 92704
      • Helping Hands Medical Associates INC
  • Colorado
    • Colorado Springs, Colorado, United States, 80923
      • St Francis Medical Center
    • Lakewood, Colorado, United States, 80228
      • Colorado Heart and Vascular .
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates PC
  • Connecticut
    • West Hartford, Connecticut, United States, 06109
      • Hartford Healthcare Headache Center
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System
  • Delaware
    • Newark, Delaware, United States, 19713
      • Cardiology Physicians PA .
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health .
    • Hialeah, Florida, United States, 33016
      • New Generation of Medical Research Avera Health N Central Heart
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center
    • Sarasota, Florida, United States, 34239
      • Intercoastal Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30310
      • Morehouse School of Medicine
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine/Winship Cancer Institute
    • Augusta, Georgia, United States, 30901
      • University Cardiology Associates
  • Idaho
    • Boise, Idaho, United States, 83702
      • St Lukes Idaho Cardiology Associates CLCZ696BUS13
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago .
    • Elk Grove Village, Illinois, United States, 60007
      • AMITA Health
    • Oakbrook Terrace, Illinois, United States, 60181
      • Midwest Cardiovascular Institute .
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group .
    • Peoria, Illinois, United States, 61614
      • OSF Healthcare
    • Peoria, Illinois, United States, 61606
      • Unity Point Health Methodist
    • Winfield, Illinois, United States, 60190
      • Northwestern Medicine Northwestern University
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Midwest Cardiovascular Research and Education Foundation .
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Services Research Center .
    • Muncie, Indiana, United States, 47303
      • Indiana University Health
    • Richmond, Indiana, United States, 47374
      • Reid Hosp And Hlth Care Services
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The Uni of Kansas Medical Center
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Alexandria Cardiology Clinic
    • Baton Rouge, Louisiana, United States, 70808
      • The Franciscan Missionaries
  • Maine
    • Bangor, Maine, United States, 04401
      • Northern Light Easter Maine Medical Center .
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Univ School of Med
    • Salisbury, Maryland, United States, 21804
      • Tidal Health Peninsula Regional Inc .
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Univeristy Medical Center .
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr CLCZ696D2301
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hs
    • Detroit, Michigan, United States, 48201
      • Detroit Medical Center Cardiovascular Clinical Trial .
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital Cardiovascular Medicine
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health Michigan Heart .
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Novartis Investigative Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Jackson Heart Clinic
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Heart Institute CHI Health Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89201
      • Univ Medical Center Las Vegas
    • Reno, Nevada, United States, 89502
      • R Ins For Heart And Vascular Health
  • New Jersey
    • Elmer, New Jersey, United States, 08318
      • Inspira Health Network
    • Haddon Heights, New Jersey, United States, 08035
      • Cooper University Health Care
    • Newark, New Jersey, United States, 07102
      • Saint Michael Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Cedar Multi-Specialty Clinic
  • New York
    • Albany, New York, United States, 12205
      • Albany Associates In Cardiology
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center .
    • Flushing, New York, United States, 11355
      • New York Presbyterian Queens .
    • Johnson, New York, United States, 13790
      • United Health Services Office Of Clinical Trails CLCZ696BUS01
    • Manhasset, New York, United States, 11030
      • Northwell Health .
    • New York, New York, United States, 10029
      • Mount Sinai Hospital .
    • Poughkeepsie, New York, United States, 12601
      • HealthQuest
    • Roslyn, New York, United States, 11576
      • Catholic Hlth Svcs of Long Island
    • Staten Island, New York, United States, 10310
      • Mount Sinai Health System
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center CLCZ696G2301
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7075
      • University Of North Carolina At Chapel Hill CRLX030A2209
    • Durham, North Carolina, United States, 27710
      • Duke Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation .
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
  • Oklahoma
    • Bartlesville, Oklahoma, United States, 74006
      • St John Health System
    • Tulsa, Oklahoma, United States, 74104
      • Regional Medical Labaratory
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington .
    • Natrona Heights, Pennsylvania, United States, 15065
      • Allegheny Valley Hospital .
    • Newport, Pennsylvania, United States, 17074
      • Capital Area Research LLC CACZ885M2301
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Univ Hospital .
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Regional Health Clinic Research .
    • Sioux Falls, South Dakota, United States, 57105
      • North Central Heart .
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • VA Tennessee Valley Healthcare System
  • Texas
    • Amarillo, Texas, United States, 79106
      • Pharma Tex Research .
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center .
    • Galveston, Texas, United States, 77555-1062
      • The University of Texas Medical Branch
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center CRLX030A2301
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Centra Health
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Ctr Cardiovascular Re
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-1615
      • University of Wisconsin School of Medicine and Public Health CLCZ696BUS01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

1. Signed informed consent must be obtained prior to participation in the study
2. Patients >=18 years of age, male or female

3. 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:

   1. SBP >=100mmHg for the preceding 6 hours prior to randomization; no symptomatic hypotension
   2. No increase (intensification) in IV diuretic dose within last 6 hours prior to randomization
   3. No IV inotropic drugs for 24 hours prior to randomization
   4. No IV vasodilators including nitrates within last 6 hours prior to randomization
4. HFpEF with most recent LVEF > 40% (within past 3 months)

5. 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):

   1. 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
   2. Patients recruited in-hospital were randomized based on the qualifying local lab value in-hospital NT-proBNP or BNP value.
   3. Patients enrolled post-decompensation can be randomized based on their NT-proBNP or BNP value in the following way:

   i. 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

EXCLUSION CRITERIA:

1. 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%
2. Entresto™ (sacubitril/valsartan) usage within the past 60 days
3. 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
4. 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
5. 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
6. 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.
7. Isolated right HF in the absence of left-sided structural heart disease
8. 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
9. Patients with a known history of angioedema due to any etiology
10. 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
11. A cardiac or non-cardiac medical condition other than HF with an estimated life expectancy of < 6 months
12. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy including suspected or confirmed amyloid heart disease (amyloidosis)
13. Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate > 110 bpm
14. Clinically significant congenital heart disease felt to be the cause of the patient's symptoms and signs of HF
15. Coronary or carotid artery disease or valvular heart disease likely to require surgical or percutaneous intervention within the duration of the trial
16. 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
17. 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
18. Participation in any other clinical trial involving investigational agents or devices within the past 30 days
19. Current confirmed COVID19 infection
20. Past COVID19 infection with persistent symptom burden suspected due to COVID19 (further defined in Section 5.2).
21. 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.
22. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sacubitril/valsartan (LCZ696); 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)	Drug: sacubitril/valsartan; 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; Other Names: LCZ696; Drug: valsartan matching placebo; Valsartan matching placebo was available as tablet form to be taken orally, twice daily
Active Comparator: valsartan; 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)	Drug: valsartan; Valsartan was available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily; Drug: sacubitril/valsartan matching placebo; Sacubitril/valsartan (LCZ696) matching placebo was available as tablet form to be taken orally, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Average of Week 4 and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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	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%)	Up to week 84

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available at www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2019
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 14, 2022

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Acute decompensated heart failure; Heart failure with preserved ejection fraction (HFpEF); NT-proBNP; NYHA; Worsening Heart Failure; Sacubitril/valsartan; Heart failure hospitalization; Global evaluation of treatment effectiveness (GETE)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696DUS01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No