The ENCHANTMENT HIV Study

Ending Subclinical Heart Failure Using an Aldosterone and Natriuretic Peptide Targeted Treatment in HIV--The ENCHANTMENT HIV Study

Persons with HIV, even those well-treated, are at increased risk for heart disease when compared to the general population. Two hormones called aldosterone and brain natriuretic peptide (BNP), which have been shown to be abnormal in HIV, may be associated with inflammation as well as early changes in structure and function of the heart. This study is being conducted to evaluate whether therapies to block aldosterone and increase BNP levels may reduce the burden and progression of heart failure to improve cardiovascular health.

Study Overview

• Status: Completed
• Conditions: HIV/AIDS; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Sacubitril-Valsartan 49-51Mg Oral Tablet; Drug: Placebo oral tablet

Detailed Description

This is a 6-month study enrolling persons with HIV with no known history of heart disease. Participants will be screened for early signs of heart failure using cardiac ultrasound (cardiac transthoracic echocardiography or cardiac TTE). Those participants who have early changes in the structure and function of the heart and may be at future risk for heart failure will be enrolled into the study. Additional imaging of the heart will occur using cardiac magnetic resonance imaging (cardiac MRI). Following baseline studies, participants will either receive a medication called sacubitril/valsartan or placebo for 6 months. Sacubitril/valsartan in an FDA approved medication currently being used for heart failure with reduced ejection fraction in the general population, and we are evaluating whether this medication could be useful to reduce HIV-related heart failure with preserved ejection fraction. Sacubitril/valsartan is an oral medication taken twice daily that may block aldosterone hormone and increase natriuretic peptide hormone. Overall, this study aims to investigate the effect of sacubitril/valsartan on measures of heart disease related to inflammation, structure and function of the heart muscle in HIV using cardiac TTE and cardiac MRI imaging as well as blood markers of heart failure and inflammation.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Antiretroviral therapy use for >12 months
2. HIV Viral Load <200 copies/mL
3. Left Ventricular Ejection Fraction>50%

4. Demonstration of one or more criteria for myocardial dysfunction on cardiac transthoracic echocardiogram, relevant to the progression of heart failure with preserved ejection fraction:

   • Left Atrial Volume Index > 28 mL/m2
   • Global Longitudinal Strain <18%
   • Left Ventricular Mass Index > 95g/m2 (female), 115 g/m2 (male)

Exclusion Criteria:

1. Known history of congestive heart failure or valvular disease
2. Recent cardiac event or stroke within 3 months
3. Current medication use acting along the RAAS pathway (ACEi, ARB, MR blockade, direct renin inhibitor), potassium (K) supplementation or diuretic
4. Angioedema to ACEi or ARB
5. SBP<100 mmHg
6. Medication suspected to have contraindication with active study drug
7. Steroid use within last 3 months
8. Uncontrolled diabetes requiring insulin and/or HbA1c > 7.5%
9. Creatinine (Cr)>1.5 mg/dL and estimated GFR<60 mL/min/1.73m2
10. K>5.5 mEq/L
11. Hemoglobin <10.0 g/dL
12. Known liver disease or ALT>3x upper limit normal
13. Pregnant, actively seeking pregnancy or breastfeeding
14. Estrogen, progestin derivative, or other sex steroid use within 3 months. Stable physiologic testosterone replacement (> 3 months) is acceptable
15. Current bacterial or other infection
16. Active substance abuse
17. Known reaction to gadolinium

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacubitril/Valsartan; Sacubitril/Valsartan 49-51mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months	Drug: Sacubitril-Valsartan 49-51Mg Oral Tablet; By mouth twice daily; Other Names: Entresto
Placebo Comparator: Placebo; Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months	Drug: Placebo oral tablet; Placebo oral tablet By mouth twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Inflammation/Fibrosis	Myocardial Inflammation/Fibrosis measured by extracellular volume fraction via cardiac magnetic resonance imaging	6 months
Myocardial Dysfunction	Left Atrial Volume Index or Global Longitudinal Strain measured by cardiac transthoracic echocardiography	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other Indices of Myocardial Dysfunction	Alterations in other cardiac structure and function as measured by cardiac magnetic resonance imaging or cardiac transthoracic echocardiogram	6 months
Markers of Myocardial Inflammation and Fibrosis	Circulating biomarkers of myocardial inflammation and fibrosis	6 months
Cardiac Natriuretic Peptides	Circulating cardiac natriuretic peptides	6 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, Lo J, Adler GK, Grinspoon SK. RAAS Activation Is Associated With Visceral Adiposity and Insulin Resistance Among HIV-infected Patients. J Clin Endocrinol Metab. 2015 Aug;100(8):2873-82. doi: 10.1210/jc.2015-1461. Epub 2015 Jun 18.
• Murphy CA, Fitch KV, Feldpausch M, Maehler P, Wong K, Torriani M, Adler GK, Grinspoon SK, Srinivasa S. Excessive Adiposity and Metabolic Dysfunction Relate to Reduced Natriuretic Peptide During RAAS Activation in HIV. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1558-1565. doi: 10.1210/jc.2017-02198.
• Srinivasa S, Fitch KV, Wong K, O'Malley TK, Maehler P, Branch KL, Looby SE, Burdo TH, Martinez-Salazar EL, Torriani M, Lyons SH, Weiss J, Feldpausch M, Stanley TL, Adler GK, Grinspoon SK. Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2376-2384. doi: 10.1210/jc.2018-00330.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): July 9, 2025
• Study Completion (Actual): July 9, 2025

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 3, 2019
• First Posted (Actual): November 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HIV; Cardiovascular Disease; Heart Failure with Preserved Ejection Fraction; Aldosterone; Myocardial Dysfunction; Natriuretic Peptides; Sacubitril/valsartan
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Cardiovascular Diseases; Acquired Immunodeficiency Syndrome; Pharmaceutical Preparations; Dosage Forms; Tablets; sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: MGH2019P002355

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No