The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03190304
• Date of registration: 14/06/2017
• Prospective Registration: Yes
• Primary sponsor: University of Sao Paulo General Hospital
• Public title: The Effect of Neprilysin (LCZ696) on Exercise Tolerance in Patients With Heart Failure NEPRIExTol
• Scientific title: The Effect of NEPRIlysin (LCZ696) on EXercise TOLerance, Muscle Vasodilatation, Muscle Strength and Body Composition in Patients With Heart Failure - NEPRIExTol-HF Trial
• Date of first enrolment: June 14, 2017
• Target sample size: 52
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03190304
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Brazil

Contacts

• Name: Antonio P Barretto, PhD
• Affiliation: Heart Institute (InCor), University of Sao Paulo Medical School

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Symptomatic patients with heart failure (men and women) aged >18 years,

2. Functional class II, III or IV by the New York Heart Association (NYHA)

3. Left ventricular ejection fraction <35%

4. Ischemic and nonischemic etiology

5. Type B natriuretic peptide (BNP) >150 pg/ml (or pro-BNP [N-terminal-proBNP] = 600 pg /
ml) or if the patient was hospitalized for cardiac decompensation within the preceding
12 months, BNP >100 pg/ml (or N-terminal-proBNP = 400 pg / ml)

Exclusion Criteria:

1. History of hypersensitivity or allergy to any of the study drugs, drugs of similar
chemical classes, ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or
neprilysin inhibitors, as well as known or suspected contraindications to the study
drugs.

2. Previous history of intolerance to recommended target doses of ACEIs or ARBs.

3. Known history of angioedema.

4. Requirement for treatment with both ACEIs and ARBs.

5. Current acute decompensated heart failure (exacerbation of chronic heart failure
manifested by signs and symptoms that may require intravenous therapy).

6. Symptomatic hypotension.

7. Estimated glomerular filtration rate (eGFR) <30%.

8. Serum potassium >5.4 mmol/L.

9. Acute coronary syndrome, stroke, transient ischaemic attack, cardiac, carotid, or
other major cardiovascular surgery, percutaneous coronary intervention, or carotid
angioplasty within the 3 months.

10. Coronary or carotid artery disease likely to require surgical or percutaneous
intervention within the 6 months.

11. Implantation of a cardiac resynchronization therapy (CRT) device within 3 months or
intent to implant a CRT.

12. History of heart transplant or on a transplant list or with left ventricular (LV)
assistance device.

13. History of severe pulmonary disease.

14. Diagnosis of peripartum- or chemotherapy-induced cardiomyopathy within the 12 months.

15. Documented untreated ventricular arrhythmia with syncopal episodes within the 3
months.

16. Symptomatic bradycardia or second- or third-degree atrioventricular block without a
pacemaker.

17. Presence of haemodynamically significant mitral and/or aortic valve disease, except
mitral regurgitation secondary to LV dilatation.

18. Presence of other haemodynamically significant obstructive lesions of the LV outflow
tract, including aortic and subaortic stenosis.

19. Any surgical or medical condition which might significantly alter the absorption,
distribution, metabolism, or excretion of study drugs, including, but not limited to,
any of the following: History of active inflammatory bowel disease during the 12
months. Active duodenal or gastric ulcers during the 3 months. Evidence of hepatic
disease as determined by any one of the following: aspartate aminotransferase or
alanine aminotransferase values exceeding 2x upper limit of normal, history of hepatic
encephalopathy, history of oesophageal varices, or history of porto-caval shunt.
Current treatment with cholestyramine or colestipol resins.

20. Presence of any other disease with a life expectancy of <5 years.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Heart Failure

Exercise Tolerance

Vasodilation

Body Composition

Muscle Strength

Intervention(s)

Drug: Neprilysin

Drug: Enalapril

Primary Outcome(s)

Exercise tolerance [Time Frame: 6 months]

Secondary Outcome(s)

Muscle strength [Time Frame: 6 months]

Walking distance [Time Frame: 6 months]

Body composition [Time Frame: 6 months]

Muscle vasodilation [Time Frame: 6 months]

Secondary ID(s)

NEPRIExTol-HF Trial

Source(s) of Monetary Support

Please refer to primary and secondary sponsors