NATriuretic Response to Expansion and dIUretics in huMans With Heart Failure

• Status: Not yet recruiting
• Trial end date: 2021-07-31
• Target enrollment: 0
• Participant gender: All

Summary

NATRIUM-HF is a multicenter, non-randomized, pre-post intervention study designed to assess renal response to intravascular fluid expansion and diuretics after sacubitril/valsartan (Entresto®) in euvolemic heart failure patients with reduced ejection fraction. Approximately 230 eligible patients will attend one visit prior to and visits 2 and 3 months after starting Entresto®. At each visit, the patient's responses to extravascular fluid expansion with Ringer's solution and to a loop diuretic bolus will be measured. Biomarkers measured in blood and urine samples will include natriuretic peptides (NP) B-type NP (BNP) and N-terminal proBNP (NT-proBNP), NP fragments, neprilysin activity and concentration, and other biomarkers related to heart failure.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Momentum Research, Inc.
• Collaborators: Abbott; Saint-Louis-Lariboisière University Hospitals
• Treatments: Calcium; Calcium, Dietary; Diuretics; Furosemide; Sodium Potassium Chloride Symporter Inhibitors

Criteria

Inclusion criteria:

1. Male or female patients ≥ 18 and < 80 years of age.

2. Ambulatory patients with a diagnosis of stable NYHA class II heart failure with left ventricular ejection fraction <40 %, for whom sacubitril/valsartan (Entresto®) is indicated as recommended by ESC guidelines and are about to be switched to Entresto® therapy.

3. Stable oral doses of ACEi or ARB, beta-blocker, mineralocorticoid antagonist (MRA), and loop diuretic (up to 120 mg daily furosemide or equivalent*) for > 3 months prior to Screening, except where intolerance or contraindication documented.

4. Stable HF without any recent exacerbation of symptoms and/or signs of HF, admission for HF, unplanned clinic visit or emergency service visit for HF or need for significant up titration or new administration of oral or IV diuretics, renin-angiotensin system (RAAS) blockers (including ACEi, ARB, and/or MRA) and/or beta blockers for > 3 months.

5. Euvolemia as defined by no signs of congestion (pulmonary rales or >1+ peripheral edema) by physical examination.

6. Written informed consent to participate in the study.

7. Ability to comply with all study requirements, without major morbidities compromising the patient's ability to participate and understand the study for 90 days.

Exclusion criteria:

1. Significant pulmonary disease contributing substantially to the patients' dyspnea such as FEV1< 1 liter or need for chronic steroid therapy.

2. Myocardial infarction, unstable angina, ICD or CRT implantation, or cardiac surgery, including percutaneous transluminal coronary intervention, within past 3 months.

3. History of heart transplant or on a transplant list, or using or planned to be implanted with a ventricular assist device.

4. Sustained ventricular arrhythmia with syncopal episodes within past 3 months that is untreated.

5. Presence of any hemodynamically significant valvular stenosis or regurgitation, except mitral or tricuspid regurgitation secondary to left ventricular dilatation. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract.

6. Stroke or TIA within the past 3 months

7. Primary liver disease considered to be life threatening.

8. Any episode of symptomatic hypotension within 3 months prior to screening.

9. Known history of angioedema with ACEi or ARB use, or history of hereditary or idiopathic angioedema.

10. Coagulation or bleeding disorder.

11. Systolic blood pressure < 100 mmHg.

12. Serum sodium > 146 mEq/L (146 mmol/L).

13. Serum potassium > 5.2 mEq/L (5.2 mmol/L) or < 3.5 mEq/L (3.5 mmol/L).

14. Renal disease or eGFR < 30 ml/min/1.73m2 (as measured by the simplified MDRD formula).

15. Ultrafiltration or dialysis within 3 months prior to Screening.

16. Hypersensitivity to sacubitril, valsartan, or any of the excipients in Entresto®; or hypersensitivity to furosemide.

17. History or presence of any other diseases (i.e. including malignancies) with a life expectancy of < 3 months.

18. Participation in any CHF trial or any investigational drug or device study within the 30 days prior to Screening.

19. History of noncompliance to medical regimens and patients who are considered potentially unreliable.

20. Pregnant or nursing (lactating) women.

21. Active infection based on abnormal temperature and elevated WBC count.

22. Receipt of blood transfusion within 3 months prior to Screening.

23. Current use of any drug containing a direct renin inhibitor (aliskiren) or neprilysin inhibitor (sacubitril).

• Equivalent oral loop diuretic doses will be considered as 1 mg bumetanide=20 mg torsemide=80 mg furosemide