EntrestoTM (LCZ696) In Advanced Heart Failure (LIFE Study)

• Status: Completed
• Trial end date: 2020-09-29
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study is to determine whether, in patients with symptomatic, advanced heart failure due to left ventricular systolic dysfunction, treatment with LCZ696 for 24 weeks will improve Pro-B-type Natriuretic Peptide (NT-proBNP) levels, which reflect hemodynamic and clinical status, compared to treatment with valsartan.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: LCZ 696; Sacubitril and valsartan sodium hydrate drug combination; Valsartan

Criteria

Inclusion Criteria:

1. Advanced HFrEF defined as including ALL

1. LVEF≤ 35% documented during the preceding 12 months

2. NYHA class IV symptomatology, defined as chronic dyspnea or fatigue at rest or on minimal exertion in the previous 3 months, or patients who require chronic inotropic therapy

3. Minimum of 3 months GDMT for HF and/or intolerant to therapy

2. Systolic blood pressure ≥ 90 mmHg

3. Serum NT-proBNP ≥ 800 pg/mL OR BNP ≥ 250 pg/mL (most recent - less than 3 months old)

4. Any one or more of the following objective findings of advanced HF including:

1. Current inotropic therapy or use of inotropes in the past 6 months

2. ≥ 1 hospitalization for heart failure in the past 6 months (not including the index hospitalization for inpatient participants)

3. LVEF ≤ 25% (within the past 12 months)

4. Peak VO2 < 55% predicted or peak VO2 ≤ 16 for men or ≤ 14 for women (Respiratory Exchange Ratio (RER) ≥ 1.05) (within the past 12 months)

5. 6 min walk test distance < 300 m (within the past 3 months)

5. Age ≥18 years and ≤ 85 years

6. Signed Informed Consent form

Exclusion Criteria:

1. Currently taking Entresto™

2. History of hypersensitivity or intolerance (unmodifiable) to Entresto™, an ACEI or ARB as well as known or suspected contraindications (including hereditary angioedema) to the study drugs.

3. Estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 at baseline

4. Co-morbid conditions that may interfere with completing the study protocol (e.g. recent history of drug or alcohol abuse) or cause death within 1 year

5. Symptomatic hypotension at randomization or systolic blood pressure < 90 mmHg

6. Serum potassium > 5.5 mmol/L

7. Severe liver dysfunction (Childs-Pugh Class C)

8. Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)

9. Planned or recent (≤ 4 weeks) PCI, coronary artery bypass grafting, or biventricular pacing

10. Currently hospitalized and listed status 1A, 1B or 1-4 for heart transplant

11. Current or scheduled for LVAD implantation within 30 days of study enrollment

12. Active infection (current use of oral or IV antimicrobial agents)

13. Primary hypertrophic or infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade

14. Complex congenital heart disease

15. Concomitant use of aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min/1.73 m²)

16. Known pregnancy or anticipated pregnancy within the next 6 months or breastfeeding mothers

17. Enrollment in any other investigational clinical trial within 30 days prior to screening

18. Inability to comply with study procedures