MANP + Sacubitril/Valsartan for Heart Failure

Overseen By Sherry Benike, RN, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Horng Chen

Must be taking: Chronic diuretics

Disqualifiers: Diabetes, BMI > 35, others

Compensation: Varies

Number of Visits: 5

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests two drugs, Sacubatril/Valsartan and MANP, in people with a challenging type of heart failure and kidney disease. Sacubatril/Valsartan helps relax blood vessels, while MANP may help the heart and kidneys by removing extra salt and water. The goal is to see if these treatments can improve symptoms and heart function.

Will I have to stop taking my current medications?

The trial requires participants to stay on a stable dose of their current diuretic medication for at least 4 weeks before the study and throughout its duration. The protocol does not specify other medication changes, so it's best to discuss your specific medications with the study team.

Is the combination of MANP and Sacubitril/Valsartan safe for heart failure treatment?

Sacubitril/Valsartan is generally considered safe for treating heart failure, with side effects similar to other heart failure medications. However, there is a potential risk of angioedema (swelling under the skin) and possible cognitive effects, which need further study, especially in certain populations. ^{1 2 3 4 5}

What makes the drug MANP + Sacubitril/Valsartan unique for treating heart failure?

The drug MANP + Sacubitril/Valsartan is unique because it combines the effects of sacubitril/valsartan, which enhances natriuretic peptides (hormones that help regulate blood pressure and fluid balance), with MANP, potentially offering a novel approach to managing heart failure by targeting multiple pathways involved in heart function. ^{6 7 8 9 10}

Research Team

Paul M McKie

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with heart failure that still have a normal amount of blood pumped from the heart (HFpEF) and also have chronic kidney disease, but not diabetes or severe obesity. They must be on stable diuretic medication and have certain levels of kidney function and symptoms according to NYHA class.

Inclusion Criteria

I do not have diabetes and my BMI is 35 or less.

I have heart failure with moderate symptoms and am on long-term water pills.

I have been on a stable dose of a diuretic for at least 4 weeks.

Exclusion Criteria

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

Received an investigational drug within 1 month prior to dosing

I have been diagnosed with constrictive pericarditis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Diet Compliance and Medication Adjustment

Participants receive diet instructions and medication adjustments prior to the active study phase

1 week

1 visit (in-person)

Crossover Treatment

Participants undergo three crossover treatment visits with different drug/placebo combinations, each followed by a washout period

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MANP
• Sacubitril/Valsartan

Trial Overview The study tests two drugs: Sacubitril/Valsartan (Entresto) and MANP, against placebos to see how they affect people with HFpEF-CKD who get short of breath during exercise without signs of fluid retention. Participants will receive either one drug or placebo through oral or injection routes.

Participant Groups

Group I: HFpEF-EI with Sacbitril/Valsartan with an injected placebo Experimental Treatment 2 Interventions

Subjects with with HFpEF with exercise induced dyspnea (difficult or labored breathing) without clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug Sacbitril/Valsartan and an injected placebo followed by a 1 week washout period.

Group II: HFpEF-EI with MANP and oral placebo Experimental Treatment 2 Interventions

Subjects with with HFpEF with exercise induced dyspnea (difficult or labored breathing) without clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug MANP and an oral placebo followed by a 1 week washout period.

Group III: HFpEF-CKD with Sacbitril/Valsartan with an injected placebo Experimental Treatment 2 Interventions

Subjects with with HFpEF volume overload in the presence of chronic kidney diseases and clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug Sacbitril/Valsartan and an injected placebo followed by a 1 week washout period.

Group IV: HFpEF-CKD with MANP and oral placebo Experimental Treatment 2 Interventions

Subjects with with HFpEF volume overload in the presence of chronic kidney diseases and clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive study drug MANP and an oral placebo followed by a 1 week washout period.

Group V: HFpEF-EI with an oral and injected placebo Placebo Group 2 Interventions

Subjects with with HFpEF with exercise induced dyspnea (difficult or labored breathing) without clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive an oral and injected placebo followed by a 1 week washout period.

Group VI: HFpEF-CKD with an oral and injected placebo Placebo Group 2 Interventions

Subjects with with HFpEF volume overload in the presence of chronic kidney diseases and clinical symptoms at rest (e.g. peripheral edema, weight gain, and abdominal distention) will receive an oral and injected placebo followed by a 1 week washout period.

Who Is Running the Clinical Trial?

Horng Chen

Lead Sponsor

Trials

4

Recruited

170+

Findings from Research

In a study of 30 patients with chronic heart failure, treatment with sacubitril/valsartan for 12 months led to a significant improvement in left ventricular ejection fraction, increasing from a median of 26.3% to 36.3%.

The study also monitored NT-proBNP levels and glomerular filtration rates, indicating that sacubitril/valsartan not only improves heart function but may also positively impact other cardiovascular health markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the dynamics of clinical and laboratory markers of chronic heart failure during 12 months of sacubitril/valsartan treatment. Čepelová, J., Malý, M., Daněk, J., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Will sacubitril-valsartan diminish the clinical utility of B-type natriuretic peptide testing in acute cardiac care? [2021]

2. England pubmed.ncbi.nlm.nih.gov

The safety of sacubitril-valsartan for the treatment of chronic heart failure. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Sacubitril/valsartan and loop diuretic requirement in heart failure with preserved ejection fraction in the PARAGON-HF trial. [2023]

4. Japan pubmed.ncbi.nlm.nih.gov

Long-Term Treatment With Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction - Open-Label Extension of the PARALLEL-HF Study. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Cognitive performance of patients with chronic heart failure on sacubitril/valsartan : A retrospective cohort study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

proANP Metabolism Provides New Insights Into Sacubitril/Valsartan Mode of Action. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Acute pulmonary pressure change after transition to sacubitril/valsartan in patients with heart failure reduced ejection fraction. [2021]

9. Czech Republic pubmed.ncbi.nlm.nih.gov

Monitoring the dynamics of clinical and laboratory markers of chronic heart failure during 12 months of sacubitril/valsartan treatment. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Association of Change in N-Terminal Pro-B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction. [2022]