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)

  • STATUS
    Recruiting
  • End date
    Oct 29, 2022
  • participants needed
    800
  • sponsor
    Novartis Pharmaceuticals
Updated on 12 December 2021

Summary

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.

Details
Condition Heart Failure With Preserved Ejection Fraction (HFpEF)
Treatment Valsartan, sacubitril/valsartan
Clinical Study IdentifierNCT03988634
SponsorNovartis Pharmaceuticals
Last Modified on12 December 2021

Eligibility

Yes No Not Sure

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
No i.v. inotropic drugs for 24 hours prior to randomization
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
if enrolling in out-of-hospital setting then need eligible screening/local
BNP ≥ 150 pg/mL; patients in AF at the time of biomarker assessment: NT-proBNP ≥
pg/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
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
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
Body mass index (BMI) > 50 kg/m2 at randomization
the LVEF (i.e., MI, CABG), unless an echo measurement was performed after the event
Isolated right HF in the absence of left-sided structural heart disease
confirming the LVEF to be >40%
Currently taking Entresto™ (sacubitril/valsartan) or any prior use
Patients with a known history of angioedema due to any etiology
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
Current confirmed COVID19 infection
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 within 30 days prior to
randomization or
Female sterilization (have had surgical bilateral oophorectomy with or without
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 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
Past COVID19 infection with persistent symptom burden suspected due to COVID19
Persistent symptoms may include, but are not limited to, continued cough, breathing
difficulty, muscle/joint aches, and gastrointestinal symptoms from the time of COVID19
infection onward
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 childbearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using basic methods of contraception during dosing
of study treatment. Basic contraception methods include
Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking
investigational drug. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the
study, the vasectomized male partner should be the sole partner for that patient
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault
caps)
Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy
(failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception
or placement of an intrauterine device (IUD) or intrauterine system (IUS)
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