50 Participants Needed

Sacubitril-Valsartan for Heart Failure in HIV

SS
Overseen BySuman Srinivasa, MD, MS
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially those that affect the RAAS pathway (like ACE inhibitors, ARBs, or MR blockers), potassium supplements, or diuretics, as they are not allowed in this trial.

What data supports the effectiveness of the drug Sacubitril-Valsartan for heart failure in HIV patients?

Research shows that Sacubitril-Valsartan significantly improves heart health and quality of life in patients with heart failure and reduced ejection fraction, which means the heart pumps less blood with each beat. This suggests it could be beneficial for heart failure in HIV patients as well.12345

Is Sacubitril-Valsartan generally safe for humans?

Sacubitril-Valsartan has been studied for heart failure and is generally considered safe, but some patients may stop using it due to side effects, and a small percentage may experience serious outcomes.46789

How is the drug Sacubitril-Valsartan unique for treating heart failure in HIV patients?

Sacubitril-Valsartan is unique because it combines two actions: it blocks a hormone that narrows blood vessels and inhibits an enzyme that breaks down beneficial proteins, which helps improve heart function. This dual action is different from many other heart failure treatments that typically focus on just one mechanism.1451011

Eligibility Criteria

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.

Inclusion Criteria

Your heart's ability to squeeze and relax is less than 18%.
Your heart is too big for your body size.
Your left atrium is too big for this study.
See 4 more

Exclusion Criteria

My kidney function is reduced with creatinine over 1.5 mg/dL and GFR under 60.
Your blood pressure is less than 100 mmHg.
Your blood potassium level is higher than 5.5 milliequivalents per liter.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Baseline Assessment

Baseline cardiac imaging and blood tests to assess heart structure and function

1 week
1 visit (in-person)

Treatment

Participants receive sacubitril/valsartan or placebo for 6 months with lifestyle modification counseling

6 months
Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
1 visit (in-person)

Treatment Details

Interventions

  • Placebo oral tablet
  • Sacubitril-Valsartan 49-51Mg Oral Tablet
Trial OverviewThe 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.
Participant Groups
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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials
3,066
Recruited
13,430,000+

Findings from Research

In a study involving 84 healthy male subjects, both therapeutic (400 mg) and supratherapeutic (1200 mg) doses of sacubitril/valsartan (LCZ696) did not significantly affect cardiac repolarization, as indicated by QTcF intervals remaining within safe limits.
The study confirmed the safety of LCZ696, with no significant changes in ECG parameters or increased adverse events compared to placebo, supporting its use in patients with chronic heart failure.
Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.Langenickel, TH., Jordaan, P., Petruck, J., et al.[2021]
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.
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]
In a retrospective study of 132 heart failure patients with reduced ejection fraction, those treated with sacubitril/valsartan showed significant improvements in both left ventricular ejection fraction (LVEF) and global left ventricular longitudinal strain (GLS) over an average of 14 months, indicating enhanced heart function.
Unlike the control group receiving conventional therapy, which only improved LVEF, the sacubitril/valsartan group demonstrated a notable increase in GLS, suggesting that this medication may offer additional benefits in heart remodeling beyond just improving ejection fraction.
Sacubitril/valsartan improves left ventricular longitudinal deformation in heart failure patients with reduced ejection fraction.De Vecchis, R., Paccone, A., Di Maio, M.[2023]

References

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization. [2021]
2.Czech Republicpubmed.ncbi.nlm.nih.gov
Monitoring the dynamics of clinical and laboratory markers of chronic heart failure during 12 months of sacubitril/valsartan treatment. [2021]
Sacubitril/valsartan improves left ventricular longitudinal deformation in heart failure patients with reduced ejection fraction. [2023]
Sacubitril/Valsartan Averts Adverse Post-Infarction Ventricular Remodeling and Preserves Systolic Function in Rabbits. [2021]
Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. [2022]
Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials. [2022]
Sacubitril/Valsartan in Daily Clinical Practice: Data From a Prospective Registry. [2021]
Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management. [2023]
Real-World Safety of Sacubitril/Valsartan in Women and Men With Heart Failure and Reduced Ejection Fraction: A Meta-analysis. [2022]
Erratum to: Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor. [2019]
Effect of food on the oral bioavailability of the angiotensin receptor - neprilysin inhibitor sacubitril/valsartan (LCZ696) in healthy subjects . [2022]