NCT04153136

Brief 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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
39

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Sep 2020

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 30, 2019

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 6, 2019

Completed
10 months until next milestone

Study Start

First participant enrolled

September 11, 2020

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 9, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 9, 2025

Completed
Last Updated

March 11, 2026

Status Verified

March 1, 2026

Enrollment Period

4.8 years

First QC Date

October 30, 2019

Last Update Submit

March 9, 2026

Conditions

Keywords

HIVSacubitril/valsartanHeart Failure with Preserved Ejection FractionAldosteroneNatriuretic PeptidesMyocardial DysfunctionCardiovascular Disease

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (3)

  • Other Indices of Myocardial Dysfunction

    6 months

  • Markers of Myocardial Inflammation and Fibrosis

    6 months

  • Cardiac Natriuretic Peptides

    6 months

Study Arms (2)

Sacubitril/Valsartan

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo oral tablet

Interventions

By mouth twice daily

Also known as: Entresto
Sacubitril/Valsartan

Placebo oral tablet By mouth twice daily

Placebo

Eligibility Criteria

Age40 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • Known history of congestive heart failure or valvular disease
  • Recent cardiac event or stroke within 3 months
  • Current medication use acting along the RAAS pathway (ACEi, ARB, MR blockade, direct renin inhibitor), potassium (K) supplementation or diuretic
  • Angioedema to ACEi or ARB
  • SBP\<100 mmHg
  • Medication suspected to have contraindication with active study drug
  • Steroid use within last 3 months
  • Uncontrolled diabetes requiring insulin and/or HbA1c \> 7.5%
  • Creatinine (Cr)\>1.5 mg/dL and estimated GFR\<60 mL/min/1.73m2
  • K\>5.5 mEq/L
  • Hemoglobin \<10.0 g/dL
  • Known liver disease or 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

  • 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.

    PMID: 26086328BACKGROUND
  • 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.

    PMID: 29408981BACKGROUND
  • 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.

    PMID: 29659888BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency SyndromeCardiovascular Diseases

Interventions

sacubitril and valsartan sodium hydrate drug combinationTablets

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

Dosage FormsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Medicine

Study Record Dates

First Submitted

October 30, 2019

First Posted

November 6, 2019

Study Start

September 11, 2020

Primary Completion

July 9, 2025

Study Completion

July 9, 2025

Last Updated

March 11, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations