Ending Subclinical Heart Failure Using an Aldosterone and Natriuretic Peptide Targeted Treatment in HIV--The ENCHANTMENT HIV Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Myocardial Inflammation/Fibrosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Sacubitril/Valsartan
Sacubitril/Valsartan 49-51mg twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months
干预措施: Sacubitril-Valsartan 49-51Mg Oral Tablet (Drug)
Placebo
Placebo twice daily along with lifestyle modification (counseling regarding diet and healthy activity) for 6 months
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Myocardial Inflammation/Fibrosis
时间窗: 6 months
Myocardial Inflammation/Fibrosis measured by extracellular volume fraction via cardiac magnetic resonance imaging
Myocardial Dysfunction
时间窗: 6 months
Left Atrial Volume Index or Global Longitudinal Strain measured by cardiac transthoracic echocardiography
次要结局
- Other Indices of Myocardial Dysfunction(6 months)
- Markers of Myocardial Inflammation and Fibrosis(6 months)
- Cardiac Natriuretic Peptides(6 months)
研究者
Suman Srinivasa, M.D.
Assistant Professor of Medicine
Massachusetts General Hospital