Enhancing the Natriuretic Peptide System in HFpEF

• Status: Not yet recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to look at the differences in how individuals with heart failure with preserved ejection fraction in the presence of chronic kidney disease (HFpEF-CKD) and exercise induced dyspnea without objective findings of fluid retention (HFpEF-EI) bodies function using drugs Sacubatril/Valsartan (Entresto) and MANP.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Horng Chen
• Treatments: Valsartan

Criteria

Inclusion Criteria:

Group 1: HFpEF-CKD-will consist of 30 subjects with:

• Ejection fraction of greater than 55%; and

• Evidence of increased LV filling pressures, including at least 2 of the following:

average septal-lateral E/e' ratio > 15; tricuspid regurgitation (TR) peak velocity > 2:8 m/s;

• Left atrial volume index >34mL/m^2 assessed by echocardiography; and

• Previous diagnosis of HF with New York Heart Association (NYHA) functional class II-III symptoms on chronic loop diuretic therapy; and

• CKD defined as glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease equation. Subject needs to be on stable dose of chronic loop diuretic for at least 4 weeks prior to study and maintained on the same dose for the duration of the study. In addition to the exclusion criteria listed below, to ensure a more homogenous group of subjects, we will exclude subjects with Diabetes or BMI > 35 (because endogenous natriuretic peptide levels are low in obese subjects).

Group 2: HFpEF-EI-will consist of 30 subjects with:

• Ejection fraction of greater than 55%; and

• Previous invasive determination of normal pulmonary capillary wedge pressure (< 15 mmHg) at rest and ≥ 25 mmHg during exercise12; and

• New York Heart Association (NYHA) functional class II-III symptoms but not on chronic loop diuretic therapy; and

• Glomerular filtration rate (eGFR) of > 60 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease equation. In addition to the exclusion criteria listed below, to ensure a more homogenous group of subjects, we will exclude subjects with Diabetes or BMI>35 (because endogenous natriuretic peptide levels are low in obese subjects).

Exclusion Criteria:

• Body mass index > 35.

• Blood pressure < 100/60 or > 180/100 mmHg.

• Diabetes.

• Myocardial infarction within 6 months of screening.

• Unstable angina within 6 months of screening, or any evidence of myocardial ischemia.

• Significant valvular heart diseases.

• Hypertrophic, restrictive or obstructive cardiomyopathy.

• Constrictive pericarditis.

• Primary pulmonary hypertension.

• Biopsy proven active myocarditis.

• Severe congenital heart diseases.

• Cardiac amyloidosis.

• Fabry disease.

• Sarcoidosis.

• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening.

• Second or third degree heart block without a permanent cardiac pacemaker.

• Stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion.

• ALT > 2 times the upper limit of normal; serum sodium of < 135 mEq/dL or > 150 mEq/dL.

• Serum potassium of < 3.5 mEq/dL or > 5.7 mEq/dL.

• Bother acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data.

• Received an investigational drug within 1 month prior to dosing.

• Patients with an allergy to iodine; female subject who is pregnant or breastfeeding.

• In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons.