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

HIV/AIDS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04153136
• Other study ID #: MGH2019P002355
• Status: Recruiting
• Phase: Phase 2
• Start date: September 11, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: Massachusetts General Hospital
• Contact: Suman Srinivasa, MD, MS
• Phone: 6177269109
• Email: ssrinivasa[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• HIV/AIDS

Intervention

Drug:
• Sacubitril-Valsartan 49-51Mg Oral Tablet
By mouth twice daily
• Placebo oral tablet
Placebo oral tablet By mouth twice daily

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial Inflammation/Fibrosis	Myocardial Inflammation/Fibrosis measured by extracellular volume fraction via cardiac magnetic resonance imaging	6 months
Primary	Myocardial Dysfunction	Left Atrial Volume Index or Global Longitudinal Strain measured by cardiac transthoracic echocardiography	6 months
Secondary	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
Secondary	Markers of Myocardial Inflammation and Fibrosis	Circulating biomarkers of myocardial inflammation and fibrosis: Gal3, ST2, GDF15, hs-cTnT	6 months
Secondary	Cardiac Natriuretic Peptides	Circulating cardiac natriuretic peptides: ANP, BNP, NT-proBNP	6 months