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8110 Gatehouse Road, Falls Church, VA 22042

Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF (PARAGLIDE)

General Information

Age Group

Adult

Status

Recruiting

Protocol Number

CLCZ696DUS01

Background Information

The purpose of this study is to assess the effect of in-hospital initiation of sacubitril/valsartan vs. valsartan on time averaged proportional change in NT-proBNP in patients with heart failure with preserved ejection fraction who have been stabilized during hospitalization for acute decompensated heart failure.

Offered At

Inova Mount Vernon Hospital (Enrollment)
2501 Parkers Lane
Alexandria, VA 22306

Inova Cardiology – Mt. Vernon (Follow-up)
8101 Hinson Farm Road, Suite 408
Alexandria, VA 22306

Principal Investigator

Arnold Rosenblatt, MD

Eligibility Information

  1. Patients ≥ 40 years of age, male or female
  2. Currently hospitalized with acute decompensated HFpEF. 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 up to ten days after diagnosis of acute decompensation while still hospitalized as long as they meet the following definition of hemodynamically stable:
    • SBP ≥100 mm Hg 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
  3. HFpEF with most recent LVEF > 40% (within past 3 months). For EF measurements expressed as ranges, the average of the range end point values should be > 40%.
  4. Elevated NT-proBNP or BNP during current hospitalization (patients not in AF: NT-proBNP ≥ 800pg/mL or BNP ≥ 250 pg/mL; patients in AF: NT-proBNP ≥ 1600pg/mL or BNP ≥ 500 pg/mL
  5. Has not taken an ACEi for 36 hours prior to randomization

Ineligibility Information

  1. 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%
  2. Currently taking Entresto™ (sacubitril/valsartan) or any prior use
  3. eGFR < 30ml/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 of randomization
  4. Serum potassium > 5.2 mEq/L at most recent assessment prior to randomization and within 24 hours of 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 of 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. Specifically, patients with the following are excluded:
    • Severe pulmonary disease including chronic obstructive pulmonary disease (COPD) (i.e. requiring home oxygen, chronic nebulizer therapy, chronic oral steroid therapy or
    • Hemoglobin (Hgb) < 10 g/dL males and < 9.5 g/dL females or
    • Body mass index (BMI) > 50 Kg/m2 at randomization
  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 intent to implant LVAD or CRT device within the 12 week duration of the trial
  11. A cardiac or non-cardiac medical condition other than HF with an estimated life expectancy of < 3 months
  12. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy including 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 beats per minute (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 12 week 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. Pregnant or nursing women; women of childbearing potential that are not using a highly effective method of contraception until 1 week following last dose
  20. 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