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)

Completed · Phase 3 · Has a placebo group

Conditions studied: Heart Failure With Preserved Ejection Fraction (HFpEF)

In brief

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.

Key facts

Study ID

NCT03988634

Run by

Novartis Pharmaceuticals

People needed

467

Starts

2019-06-29

Expected to finish

2022-12-14

Last updated by the study team

2025-03-06

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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:
• 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).
• Has not taken an ACEi for 36 hours prior to randomization

You may not qualify if…

• 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.
• 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.

Where it is running

• Memorial Care Health System Memorialcare Long Beach — Long Beach, California, United States
• University Of Southern California . — Los Angeles, California, United States
• University Of Southern California — Los Angeles, California, United States
• San Diego Cardiac Center — San Diego, California, United States
• Zuckerberg General W84 Research . — San Francisco, California, United States
• Sutter Health Network . — San Pablo, California, United States
• Helping Hands Medical Associates INC — Santa Ana, California, United States
• St Francis Medical Center — Colorado Springs, Colorado, United States
• Colorado Heart and Vascular . — Lakewood, Colorado, United States
• South Denver Cardiology Associates PC — Littleton, Colorado, United States
• Hartford Healthcare Headache Center — West Hartford, Connecticut, United States
• VA Connecticut Healthcare System — West Haven, Connecticut, United States
• Cardiology Physicians PA . — Newark, Delaware, United States
• University of Florida Health . — Gainesville, Florida, United States
• New Generation of Medical Research Avera Health N Central Heart — Hialeah, Florida, United States
• University of Florida Health Science Center — Jacksonville, Florida, United States
• Intercoastal Medical Group — Sarasota, Florida, United States
• Morehouse School Of Medicine — Atlanta, Georgia, United States
• Emory University School of Medicine/Winship Cancer Institute — Atlanta, Georgia, United States
• University Cardiology Associates — Augusta, Georgia, United States
• St Lukes Idaho Cardiology Associates CLCZ696BUS13 — Boise, Idaho, United States
• University of Chicago . — Chicago, Illinois, United States
• Amita Health — Elk Grove Village, Illinois, United States
• Midwest Cardiovascular Institute . — Oakbrook Terrace, Illinois, United States
• University of Calif Irvine Med Cntr — Irvine, California, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.