What is the mechanism of action of this treatment?

Common treatments for heart failure, such as aldosterone blockers and BNP enhancers, work by targeting key hormonal pathways. Aldosterone blockers reduce inflammation and stress on the heart by inhibiting aldosterone, which can cause fluid retention and high blood pressure. BNP enhancers increase brain natriuretic peptide levels, aiding in blood vessel relaxation, reducing fluid buildup, and improving heart function. These treatments are vital for heart failure patients as they help manage symptoms, slow disease progression, and enhance cardiovascular health.

What side effects are associated with this type of intervention?

Common treatments for heart failure, such as aldosterone blockers (spironolactone, eplerenone) and BNP enhancers (sacubitril/valsartan), have several known side effects. Aldosterone blockers can cause hyperkalemia, particularly in older adults, and may have a theoretical risk of breast cancer, though this is not definitively proven. They also have a relatively minor impact on blood glucose levels. BNP enhancers can lead to hypotension, hyperkalemia, and renal impairment. Both types of treatments aim to reduce inflammation and heart stress, thereby improving heart function and slowing the progression of heart failure.

What prior FDA approvals exist?

The FDA has approved several treatments for heart failure that align with the mechanisms of aldosterone blockers and BNP enhancers. Spironolactone and eplerenone are aldosterone antagonists that help reduce inflammation and heart stress by blocking the effects of aldosterone. Sacubitril/valsartan (Entresto) is a combination drug that includes a neprilysin inhibitor (sacubitril) and an angiotensin receptor blocker (valsartan). Sacubitril increases levels of natriuretic peptides, including BNP, which helps improve heart function and reduce the progression of heart failure. These treatments are designed to manage heart failure by targeting hormonal pathways that contribute to cardiac stress and dysfunction.

What other types of research exist?

Promising novel alternatives for heart failure treatment in 2024 include SGLT2 inhibitors (e.g., dapagliflozin), which have shown benefits in reducing heart failure progression and improving cardiovascular outcomes. Additionally, ARNI (angiotensin receptor-neprilysin inhibitors) like sacubitril/valsartan continue to be effective in reducing heart failure-related hospitalizations and mortality. These therapies offer new mechanisms of action that complement traditional treatments by addressing multiple pathways involved in heart failure.

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Angiotensin Receptor-Neprilysin Inhibitor

Sacubitril-Valsartan for Heart Failure in HIV

Phase 2

Recruiting

Research Sponsored by Massachusetts General Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Antiretroviral therapy use for >12 months

Be older than 18 years old

Must not have

Creatinine (Cr)>1.5 mg/dL and estimated GFR<60 mL/min/1.73m2

Known liver disease or ALT>3x upper limit normal

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

Summary

This trial is testing a medication called sacubitril/valsartan in people with HIV who show early signs of heart changes. The medication aims to block a harmful hormone and increase a protective one to prevent heart problems. The study will see if this treatment can improve heart health in these patients.

Who is the study for?

This trial is for people with HIV who've been on antiretroviral therapy for over a year, have controlled viral loads, and show early signs of heart issues but no recent severe cardiac events or uncontrolled diabetes. They shouldn't be pregnant, seeking pregnancy, breastfeeding, or using certain hormones and must not have liver disease or be on medications that affect the same pathways as the study drugs.

What is being tested?

The ENCHANTMENT HIV Study tests if Sacubitril/Valsartan can help prevent heart failure in those with HIV by blocking harmful hormones and improving heart function. Participants will either receive this medication or a placebo without knowing which one they're taking to compare effects fairly.

What are the potential side effects?

Sacubitril/Valsartan may cause low blood pressure, high potassium levels, kidney problems, dizziness upon standing up too fast (orthostatic hypotension), coughing, and swelling around the eyes (angioedema). These side effects are not guaranteed but possible.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been on antiretroviral therapy for more than a year.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My kidney function is reduced with creatinine over 1.5 mg/dL and GFR under 60.

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My liver isn't working well, or my ALT levels are high.

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My diabetes is not under control and I need insulin or my HbA1c is above 7.5%.

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I am currently fighting an infection.

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I have not had a heart attack or stroke in the last 3 months.

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I am taking medication that might not mix well with the study drug.

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I have a history of heart failure or heart valve disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Myocardial Dysfunction

Myocardial Inflammation/Fibrosis

Secondary study objectives

Cardiac Natriuretic Peptides

Markers of Myocardial Inflammation and Fibrosis

Other Indices of Myocardial Dysfunction

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Sacubitril/ValsartanExperimental Treatment1 Intervention

Sacubitril/Valsartan 49-51mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months

Group II: PlaceboPlacebo Group1 Intervention

Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for heart failure, such as aldosterone blockers and BNP enhancers, work by targeting key hormonal pathways. Aldosterone blockers reduce inflammation and stress on the heart by inhibiting aldosterone, which can cause fluid retention and high blood pressure. BNP enhancers increase brain natriuretic peptide levels, aiding in blood vessel relaxation, reducing fluid buildup, and improving heart function. These treatments are vital for heart failure patients as they help manage symptoms, slow disease progression, and enhance cardiovascular health.

Aldosterone as a mediator in cardiovascular injury.