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

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: LCZ 696; Sacubitril and valsartan sodium hydrate drug combination; Valsartan

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:

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