Neprilysin Inhibition to Reduce Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 36
- 主要终点
- Change in extracellular volume by cardiac MRI
研究概览
简要总结
Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Sacubitril/valsartan reduces histological MIF in mice and levels of some extracellular matrix regulatory proteins in humans with HFpEF. However, the effect of sacubitril/valsartan on robust measures of MIF in humans is unknown. Demonstrating reductions in ECV with sacubitril/valsartan would clarify the mechanism of this approved medication. Given the borderline reduction in heart failure hospitalizations with sacubitril/valsartan and the heterogeneity of HFpEF pathophysiology, this result would suggest that neprilysin inhibition may particularly benefit HFpEF patients with greater MIF. The investigators propose a proof-of-concept clinical trial to evaluate the effect of neprilysin inhibition (sacubitril/valsartan vs valsartan alone) on cardiac MRI measures of fibrosis (principally ECV) and circulating protein levels.
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
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 50 years or older
- •Able to provide informed consent, as assessed by a physician investigator, and willing to comply with the study
- •Clinically confirmed diagnosis of heart failure
- •Left ventricular ejection fraction greater than or equal to 45% within 1 year by echocardiogram, cardiac MRI, or nuclear scan
排除标准
- •Contraindication to MRI (metal prosthesis, implantable cardiac device, or severe claustrophobia)
- •Systolic blood pressure < 100mm Hg, or <110 mm Hg for patients not taking an ACE inhibitor or angiotensin receptor blocker
- •symptomatic hypotension
- •eGFR < 30 mL/min/1.73m2 within 60 days of enrollment
- •Serum potassium >5.2mmol/L within 60 days of enrollment, or >5.0 mmol/L for patients not taking an ACE inhibitor or angiotensin receptor blocker
- •Myocardial infarction within 6 months of enrollment
- •Infiltrative or hypertrophic cardiomyopathy
- •History of cirrhosis, biliary cirrhosis, or cholestasis
- •History of angioedema
- •Pregnancy, planning pregnancy, or breastfeeding
- •Active treatment with lithium or a direct renin inhibitor
研究组 & 干预措施
Sacubitril/valsartan
Patient randomized to the interventional arm will be treated with sacubitril/valsartan
干预措施: Sacubitril-valsartan (Drug)
Valsartan
Patient randomized to the active comparator arm will be treated with valsartan
干预措施: Valsartan (Drug)
结局指标
主要结局
Change in extracellular volume by cardiac MRI
时间窗: 1 year
The primary outcome is to evaluate the change in extracellular volume (ECV), measured by cardiac MRI, from baseline to one year, in the sacubitril/valsartan arm compared to the valsartan arm
次要结局
- Change in left ventricular native T1 time(1 year)
研究者
Jonathan Cunningham MD MPH
Assistant Professor of Medicine, Cardiovascular Division
Brigham and Women's Hospital