Changes in NT-proBNP and Outcomes, Safety, and Tolerability in HFpEF Patients With Acute Decompensated Heart Failure (ADHF) Who Have Been Stabilized During Hospitalization and Initiated In-hospital or Within 30 Days Post-discharge (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 and Outcomes, Safety, and Tolerability in HFpEF Patients With Acute Decompensated Heart Failure (ADHF) Who Have Been Stabilized During Hospitalization and Initiated In-hospital or Within 30 Days Post-discharg

ClinicalTrials.gov Identifier: NCT03988634

Novartis Reference Number: CLCZ696DUS01

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to assess the effect of sacubitril/valsartan (LCZ696) vs. valsartan on changes in NT-proBNP and outcomes, safety and tolerability in patients with HFpEF (left ventricular ejection fraction (LVEF) > 40%) who have been stabilized during hospitalization for acute decompensated heart failure and initiated in-hospital or within 30 days post discharge.

Condition 
Heart Failure With Preserved Ejection Fraction (HFpEF)
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
800 participants
Start date 
Jun 27, 2019
Completion date 
Mar 21, 2022
Gender 
All
Age(s)
40 Years and older (Adult, Older Adult)

Interventions

Drug
sacubitril/valsartan
Sacubitril/valsartan (LCZ696) is available as 24/26 mg, 49/51 mg, and 97/103 mg in tablet form to be taken orally, twice daily, for the double-blind period. Valsartan matching placebo is available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily, for the double-blind period.
Drug
valsartan
Valsartan is available as 40 mg, 80 mg, and 160 mg in tablet form to be taken orally, twice daily, for the double-blind period. Sacubitril/valsartan (LCZ696) matching placebo is available as 24/26 mg, 49/51 mg, and 97/103 mg in tablet form to be taken orally, twice daily, for the double-blind period.

Eligibility Criteria

Inclusion Criteria

Signed informed consent must be obtained prior to participation in the study
Patients ≥40 years of age, male or female

Currently hospitalized for or within 30 days following discharge of an acute decompensated HFpEF admission. 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 will be randomized no earlier than 36 hours and within 30 days post-discharge after presentation with acute HFpEF decompensation and meeting the following definitions of hemodynamic stability:

In-hospital randomized patients will have been hemodynamically stable defined in this study as:

SBP≥100mmHg for the preceding 6 hours prior to randomization; no symptomatic hypotension
No increase (intensification) in i.v. diuretic dose within last 6 hours prior to randomization
No i.v. inotropic drugs for 24 hours prior to randomization
No i.v. vasodilators including nitrates within last 6 hours prior to randomization

Out-of-hospital randomization patients will have been hemodynamically stabilized defined in this study as:

SBP ≥100mmHg; no symptomatic hypotension
No increase (intensification and/or change to IV) in diuretic dose within last 24 hours prior to randomization
No i.v. inotropic drugs for 24 hours prior to randomization
HFpEF with most recent LVEF >40% (within past 3 months)

Elevated NT-proBNP or BNP at the time of screening (and within 72 hours from inhospital screening to out-of-hospital randomization, if applicable)

Patients not in 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 will be randomized based on the qualifying local lab value in-hospital NT-proBNP or BNP value. In-hospital is the preferred method of enrollment.
Patients enrolled out-of-hospital can be randomized based on their NT-proBNP or BNP value in the following way:

if enrolling in out-of-hospital 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 would require (re)drawing NT-proBNP or BNP labs in out-of-hospital setting if the lab value is not already available within the last 72 hours

Has not taken an ACEi for 36 hours prior to randomization

Exclusion Criteria

Any clinical event within the 90 days prior to randomization that could have reduced the LVEF (i.e., MI, CABG), unless an echo measurement was performed after the event confirming the LVEF to be >40%
Currently taking Entresto™ (sacubitril/valsartan) or any prior use
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 randomization
Serum potassium > 5.2 mEq/L at most recent assessment prior to randomization and within 24 hours prior to 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. Specifically, patients with the following are excluded:

Severe pulmonary disease including chronic obstructive pulmonary disease (COPD) (i.e. requiring home oxygen, oral steroid therapy) or
Hemoglobin (Hgb) < 9.5 g/dL males and < 9 g/dL females or
Body mass index (BMI) > 50 kg/m2 at randomization
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 < 12 months
Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy including 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
Pregnant or nursing women; women of childbearing potential that are not using a highly effective method of contraception until 1 week following last dose
Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment

Study Locations

United States
Novartis Investigative Site
Recruiting
Fresno, 93701
California
United States
Novartis Investigative Site
Recruiting
Long Beach, 90806
California
United States
Novartis Investigative Site
Recruiting
Los Angeles, 90033-4605
California
United States
Novartis Investigative Site
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Orange, 92868
California
United States
Novartis Investigative Site
Recruiting
San Diego, 92123
California
United States
Novartis Investigative Site
Recruiting
Littleton, 80120
Colorado
United States
Novartis Investigative Site
Recruiting
West Hartford, 06109
Connecticut
United States
Novartis Investigative Site
Recruiting
West Haven, 06516
Connecticut
United States
Novartis Investigative Site
Recruiting
Newark, 19713
Delaware
United States
Novartis Investigative Site
Recruiting
Washington, 20010-2975
District of Columbia
United States
Novartis Investigative Site
Recruiting
Fort Lauderdale, 33308
Florida
United States
Novartis Investigative Site
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Gainesville, 32610
Florida
United States
Novartis Investigative Site
Recruiting
Jacksonville, 32209
Florida
United States
Novartis Investigative Site
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Sarasota, 34239
Florida
United States
Novartis Investigative Site
Recruiting
Atlanta, 30322
Georgia
United States
Novartis Investigative Site
Recruiting
Augusta, 30901
Georgia
United States
Novartis Investigative Site
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Macon, 31201
Georgia
United States
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Boise, 83702
Idaho
United States
Novartis Investigative Site
Recruiting
Aurora, 60504
Illinois
United States
Novartis Investigative Site
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Oakbrook Terrace, 60181
Illinois
United States
Novartis Investigative Site
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Park Ridge, 60068
Illinois
United States
Novartis Investigative Site
Recruiting
Peoria, 61606
Illinois
United States
Novartis Investigative Site
Recruiting
Peoria, 61614
Illinois
United States
Novartis Investigative Site
Recruiting
Winfield, 60190
Illinois
United States
Novartis Investigative Site
Recruiting
Elkhart, 46514
Indiana
United States
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Indianapolis, 46202
Indiana
United States
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Muncie, 47303
Indiana
United States
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Richmond, 47374
Indiana
United States
Novartis Investigative Site
Recruiting
Des Moines, 50314
Iowa
United States
Novartis Investigative Site
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Kansas City, 66160
Kansas
United States
Novartis Investigative Site
Recruiting
Lexington, 40504
Kentucky
United States
Novartis Investigative Site
Recruiting
Louisville, 40205
Kentucky
United States
Novartis Investigative Site
Recruiting
Alexandria, 71301
Louisiana
United States
Novartis Investigative Site
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Baton Rouge, 70808
Louisiana
United States
Novartis Investigative Site
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Slidell, 70458
Louisiana
United States
Novartis Investigative Site
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Bangor, 04401
Maine
United States
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Annapolis, 21401
Maryland
United States
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Baltimore, 21287
Maryland
United States
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Boston, 02114
Massachusetts
United States
Novartis Investigative Site
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Boston, 02215
Massachusetts
United States
Novartis Investigative Site
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Ann Arbor, 48109
Michigan
United States
Novartis Investigative Site
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Detroit, 48201
Michigan
United States
Novartis Investigative Site
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Detroit, 48202
Michigan
United States
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Petoskey, 49770
Michigan
United States
Novartis Investigative Site
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Ypsilanti, 48197
Michigan
United States
Novartis Investigative Site
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Saint Paul, 55101
Minnesota
United States
Novartis Investigative Site
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Saint Paul, 55103
Minnesota
United States
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Jackson, 39216
Mississippi
United States
Novartis Investigative Site
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Saint Louis, 63104
Missouri
United States
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Omaha, 68198
Nebraska
United States
Novartis Investigative Site
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Reno, 89502
Nevada
United States
Novartis Investigative Site
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Camden, 08103-3117
New Jersey
United States
Novartis Investigative Site
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Elmer, 08318
New Jersey
United States
Novartis Investigative Site
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Haddon Heights, 08035
New Jersey
United States
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Newark, 07102
New Jersey
United States
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Bronx, 10461
New York
United States
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Johnson City, 13790
New York
United States
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Poughkeepsie, 12601
New York
United States
Novartis Investigative Site
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Staten Island, 10310
New York
United States
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Recruiting
Stony Brook, 11794
New York
United States
Novartis Investigative Site
Recruiting
Chapel Hill, 27599-7075
North Carolina
United States
Novartis Investigative Site
Recruiting
Greenville, 27835
North Carolina
United States
Novartis Investigative Site
Recruiting
Grand Forks, 58201
North Dakota
United States
Novartis Investigative Site
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Cincinnati, 45220
Ohio
United States
Novartis Investigative Site
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Cleveland, 44195
Ohio
United States
Novartis Investigative Site
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Toledo, 43608
Ohio
United States
Novartis Investigative Site
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Oklahoma City, 73112
Oklahoma
United States
Novartis Investigative Site
Recruiting
Tulsa, 74104
Oklahoma
United States
Novartis Investigative Site
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Abington, 19001
Pennsylvania
United States
Novartis Investigative Site
Recruiting
Camp Hill, 17011
Pennsylvania
United States
Novartis Investigative Site
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Philadelphia, 19107
Pennsylvania
United States
Novartis Investigative Site
Recruiting
Rapid City, 57701
South Dakota
United States
Novartis Investigative Site
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Nashville, 37212
Tennessee
United States
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Dallas, 75246
Texas
United States
Novartis Investigative Site
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San Antonio, 78229
Texas
United States
Novartis Investigative Site
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Burlington, 05401
Vermont
United States
Novartis Investigative Site
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White River Junction, 05009
Vermont
United States
Novartis Investigative Site
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Fairfax, 22046
Virginia
United States
Novartis Investigative Site
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Lynchburg, 24501
Virginia
United States
Novartis Investigative Site
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Richmond, 23226
Virginia
United States
Novartis Investigative Site
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Richmond, 23298
Virginia
United States
Novartis Investigative Site
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Seattle, 98122
Washington
United States
Novartis Investigative Site
Recruiting
Seattle, 98195
Washington
United States
Novartis Investigative Site
Recruiting
Tacoma, 98405
Washington
United States
Novartis Investigative Site
Recruiting
Madison, 53792-1615
Wisconsin
United States

Contacts

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Phone: 
1-888-669-6682
Name: 
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Phone: 
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Email: 

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