LIFE Study_HF

Principal Investigator: Omar Wever-Pinzon
Keywords: Entresto , heart failure Department: Div Of Cardiovascular Medicine
IRB Number: 00094944 Co Investigator: Stavros Drakos
Specialty: Cardiology, Cardiology
Sub Specialties: General Cardiology, Heart Failure
Recruitment Status: Recruiting

Contact Information

Jonathan Gutierrez
Jonathan.Gutierrez@utah.edu
8012133417

Brief Summary

Patients with advanced heart failure with reduced ejection fraction
(HFrEF) have extremely high morbidity and mortality with 1 year
outcomes of death and hospitalization of approximately 50%.1,2 For the
most advanced heart failure patients, the evidence base for medical
treatment is limited with consensus guidelines recommending
consideration for either cardiac transplant or ventricular assist device, or
palliative care. 3
The PARADIGM-HF trial showed that LCZ696, which consists of the
neprilysin inhibitor sacubitril and the ARB valsartan, improved morbidity
and mortality in patients with chronic HFrEF in comparison to enalapril.1
However, limited experience with advanced heart failure patients was
gained from patients enrolled in the trial. Additionally, experience is
needed on the use of, and outcomes with, LCZ696 in patients unable to
tolerate target doses of ACEI/ARB compared to reduced doses of
LCZ696.
 
This study will be a randomized, double-blinded trial of advanced heart
failure subjects with 1:1 randomization to either LCZ696 (sacubitril and
valsartan) or valsartan. Study drug will be administered in a doubledummy
fashion, in which subjects take active (LCZ696 or valsartan) and
placebo. Approximately 400 subjects will be randomized into the study.

Inclusion Criteria

Key inclusion criteria

 

1. Advanced HFrEF defined as including ALL

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

b. 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

c. 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:

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

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

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

d. 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)

e. 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

Exclusion Criteria

 

1. Currently taking Entresto™

 

2. History of hypersensitivity or intolerance to Entresto™, an ACEI or ARB as well as known or suspected contraindications 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 1A or 1B for 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