Clinical Trials

MainTitle

Effects of Sacubitril/Valsartan on Subclinical Heart Failure in HIV (The ENCHANTMENT HIV Study)

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified April 2020 by Suman Srinivasa, M.D., Massachusetts General Hospital

Sponsor
Massachusetts General Hospital


Information provided by (Responsible Party)
Suman Srinivasa, M.D., Massachusetts General Hospital

ClinicalTrials.gov Identifier
NCT04153136

First received: October 30, 2019
Last updated: April 10, 2020
Last Verified: April 2020
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV/AIDS
Heart Failure With Preserved Ejection Fraction

Drug : Sacubitril-Valsartan 49-51Mg Oral Tablet
Drug : Placebo oral tablet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ending Subclinical Heart Failure Using an Aldosterone and Natriuretic Peptide Targeted Treatment in HIV--The ENCHANTMENT HIV Study

Further study details as provided by Suman Srinivasa, M.D., Massachusetts General Hospital:

Primary Outcome Measures

  • Myocardial Inflammation/Fibrosis [ Time Frame: 6 months ]
    Myocardial Inflammation/Fibrosis measured by extracellular volume fraction via cardiac magnetic resonance imaging
  • Left Atrial Volume Index [ Time Frame: 6 months ]
    Left Atrial Volume Index measured by cardiac transthoracic echocardiography
Secondary Outcome Measures:
  • Indices of Myocardial Dysfunction [ Time Frame: 6 months ]
    Alterations in other cardiac structure and function as measured by cardiac magnetic resonance imaging or cardiac transthoracic echocardiogram
  • Markers of Myocardial Inflammation and Fibrosis [ Time Frame: 6 months ]
    Circulating biomarkers of myocardial inflammation and fibrosis: Gal3, ST2, GDF15, hs-cTnT
  • Cardiac Natriuretic Peptides [ Time Frame: 6 months ]
    Circulating cardiac natriuretic peptides: ANP, BNP, NT-proBNP

Estimated Enrollment: 50
Anticipated Study Start Date: June 1, 2020
Estimated Study Completion Date: February 1, 2026
Estimated Primary Completion Date: February 1, 2026 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 Name: 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

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.

Eligibility

Eligibility

Ages Eligible for Study: 40 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  1. Antiretroviral therapy use for >12 months
  2. HIV Viral Load <200 copies/mL
  3. Increased waist circumference based on NCEP criteria (male>102cm2 and female>88cm2) or increased waist to hip ratio based on WHO criteria (male>0.95 and female>0.80)
  4. Left Ventricular Ejection Fraction>50%
  5. 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:
  • 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
  • Active substance abuse
  • Known reaction to gadolinium

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT04153136

    Contacts

    Contact:   Suman Srinivasa, MD, MS 6177269109 ssrinivasa@mgh.harvard.edu

    Sponsors and Collaborators

    Massachusetts General Hospital
    More Information

    More Information


    Responsible Party: Suman Srinivasa, M.D., Assistant Professor of Medicine, Massachusetts General Hospital  
    ClinicalTrials.gov Identifier: NCT04153136   History of Changes  
    Other Study ID Numbers: MGH2019P002355  
    Study First Received: October 30, 2019  
    Last Updated: April 10, 2020  
    Individual Participant Data    
    Plan to Share IPD: No  

    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  

    Keywords provided by Suman Srinivasa, M.D., Massachusetts General Hospital:

    HIV
    Sacubitril/valsartan
    Heart Failure with Preserved Ejection Fraction
    Aldosterone
    Natriuretic Peptides
    Myocardial Dysfunction
    Cardiovascular Disease

    Additional relevant MeSH terms:
    Heart Failure
    Valsartan
    LCZ 696

    ClinicalTrials.gov processed this data on May 24, 2020
    This information is provided by ClinicalTrials.gov.