HIV/AIDSPhase 2NCT04153136
The ENCHANTMENT HIV Study
A Phase 2 study testing Sacubitril-Valsartan 49-51Mg Oral Tablet in people with HIV/AIDS and Heart Failure With Preserved Ejection Fraction, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- HIV/AIDS, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Sacubitril-Valsartan 49-51Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2020to 9 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Antiretroviral therapy use for >12 months
- HIV Viral Load <200 copies/mL
- Left Ventricular Ejection Fraction>50%
- 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)
Who cannot join
- Known history of congestive heart failure or valvular disease
- Recent cardiac event or stroke within 3 months
- Current medication use acting along the renin-angiotensin-aldosterone-system (RAAS) pathway [angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), mineralocorticoid receptor blockade, direct renin inhibitor), potassium (K) supplementation or diuretic
- Angioedema to ACEi or ARB
- Systolic blood pressure<100 mmHg
- Medication suspected to have contraindication with active study drug
Show all 17Show fewer
- Steroid use within last 3 months
- Uncontrolled diabetes requiring insulin and/or hemoglobin A1c (HbA1c) > 7.5%
- Creatinine (Cr)>1.5 mg/dL and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2
- K>5.5 mEq/L
- Hemoglobin <10.0 g/dL
- Known liver disease or alanine transaminase (ALT)>3x upper limit normal
- Pregnant, actively seeking pregnancy or breastfeeding
- Estrogen, progestin derivative, or other sex steroid use within 3 months. Stable physiologic testosterone replacement (> 3 months) is acceptable
- Current bacterial or other infection
- Active substance abuse
- Known reaction to gadolinium
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: 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.
Read the 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 Food and Drug Administration (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.
- Being tested
- Sacubitril-Valsartan 49-51Mg Oral Tablet, Placebo oral tablet
- Keywords
- HIV, Sacubitril/valsartan, Heart Failure with Preserved Ejection Fraction, Aldosterone, Natriuretic Peptides, Myocardial Dysfunction, Cardiovascular Disease
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-Valsartan 49-51Mg Oral TabletDrug
Also called Entresto
By mouth twice daily
Placebo oral tabletDrug
Placebo oral tablet By mouth twice daily
| Study group | Role | What they receive |
|---|---|---|
| Sacubitril/Valsartan | Experimental | Sacubitril/Valsartan 49-51mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months Receives: Drug: Sacubitril-Valsartan 49-51Mg Oral Tablet |
| Placebo | Placebo comparator | Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial Inflammation/Fibrosis
Change in myocardial inflammation/fibrosis measured by extracellular volume fraction via cardiac magnetic resonance imaging. Extracellular volume fraction is presented as a ratio of the volume of the extracellular compartment to the volume of the total myocardial tissue volume. A higher value indicates more inflammation/fibrosis.
Measured: Baseline and 6 months
Myocardial Dysfunction
Change in myocardial dysfunction as measured by Left Atrial Volume Index measured by cardiac transthoracic echocardiography. Left Atrial Volume Index is presented as the left atrial volume divided by body surface area. A higher value indicates more myocardial dysfunction.
Measured: Baseline and 6 Months
Secondary outcomes (3)
Other Indices of Myocardial Dysfunction
Change in myocardial fibrosis measured by T1 via cardiac magnetic resonance imaging. T1 refers to the longitudinal relaxation time. A higher T1 value indicates increased myocardial fibrosis.
Measured: Baseline and 6 Months
Markers of Myocardial Inflammation and Fibrosis
Change in serum high-sensitivity cardiac troponin (hs-cTnT)
Measured: Baseline and 6 Months
Cardiac Natriuretic Peptides
Change in serum N-terminal pro b-type natriuretic peptide (NT-proBNP)
Measured: Baseline and 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2019
- Study start11 Sep 2020
- Primary completion9 Jul 2025
- Study completion9 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Suman Srinivasa, M.D., Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04153136
- Sponsor's protocol ID
- MGH2019P002355
- Status last verified
- Sep 2026
- First submitted
- 30 Oct 2019
- Last updated
- 9 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 26086328Murphy 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.
PubMed 29408981Srinivasa 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.
PubMed 29659888
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ending Subclinical Heart Failure Using an Aldosterone and Natriuretic Peptide Targeted Treatment in HIV--The ENCHANTMENT HIV Study
- ClinicalTrials.gov ID
- NCT04153136
- Acronym / sponsor ID
- MGH2019P002355
- Keywords
- HIV, Sacubitril/valsartan, Heart Failure with Preserved Ejection Fraction, Aldosterone, Natriuretic Peptides, Myocardial Dysfunction, Cardiovascular Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 11 Sep 2020 (actual)
- Primary completion
- 9 Jul 2025 (actual)
- Study completion
- 9 Jul 2025 (actual)
- First posted
- 6 Nov 2019 (actual)
- Results
- Posted 9 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 Food and Drug Administration (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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril/Valsartan | Experimental | Drug: Sacubitril-Valsartan 49-51Mg Oral TabletSacubitril/Valsartan 49-51mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months |
| Placebo | Placebo comparator | Drug: Placebo oral tabletPlacebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Antiretroviral therapy use for >12 months
- HIV Viral Load <200 copies/mL
- Left Ventricular Ejection Fraction>50%
- Demonstration of one or more criteria for myocardial dysfunction on cardiac transthoracic echocardiogram, relevant to the progression of heart failure with preserved ejection fraction:
Key exclusion criteria (17 listed)
- Known history of congestive heart failure or valvular disease
- Recent cardiac event or stroke within 3 months
- Current medication use acting along the renin-angiotensin-aldosterone-system (RAAS) pathway [angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), mineralocorticoid receptor blockade, direct renin inhibitor), potassium (K) supplementation or diuretic
- Angioedema to ACEi or ARB
- Systolic blood pressure<100 mmHg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril-Valsartan 49-51Mg Oral TabletAlso: EntrestoBy mouth twice daily | Drug | Sacubitril/Valsartan |
| Placebo oral tabletPlacebo oral tablet By mouth twice daily | Drug | Placebo |
Primary outcome
Myocardial Inflammation/Fibrosis
Time frame: Baseline and 6 months
Change in myocardial inflammation/fibrosis measured by extracellular volume fraction via cardiac magnetic resonance imaging. Extracellular volume fraction is presented as a ratio of the volume of the extracellular compartment to the volume of the total myocardial tissue volume. A higher value indicates more inflammation/fibrosis.
Myocardial Dysfunction
Time frame: Baseline and 6 Months
Change in myocardial dysfunction as measured by Left Atrial Volume Index measured by cardiac transthoracic echocardiography. Left Atrial Volume Index is presented as the left atrial volume divided by body surface area. A higher value indicates more myocardial dysfunction.
3 secondary outcomes
Other Indices of Myocardial Dysfunction
Time frame: Baseline and 6 Months
Markers of Myocardial Inflammation and Fibrosis
Time frame: Baseline and 6 Months
Cardiac Natriuretic Peptides
Time frame: Baseline and 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26086328Srinivasa 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.
- Background: PubMed 29408981Murphy 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.
- Background: PubMed 29659888Srinivasa 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sacubitril-Valsartan 49-51Mg Oral Tablet in people with HIV/AIDS and Heart Failure With Preserved Ejection Fraction, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial Inflammation/Fibrosis (time frame: Baseline and 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04153136, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.