Spironolactone Therapy in Chronic Stable Right HF Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Change in Ventricular Wall Stress
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and mechanistic effects of spironolactone, an aldosterone receptor antagonist, on sympathetic nervous system activity and right heart function and remodeling in patients with chronic right heart failure.
详细描述
This study is a phase 4, single center, randomized, double blind, placebo-controlled trial evaluating the safety, tolerability and mechanistic effects of spironolactone, an aldosterone antagonist, on neurohormonal activity and remodeling in patients with chronic right heart failure (RHF).
RHF is one of the most important predictors of prognosis in many cardiac disease states including pulmonary hypertension (PH), and left heart failure. Sympathetic nervous system activation plays an important role in the development and progression of heart failure. It remains to be determined whether there is a role for neurohormonal therapy in chronic right HF, but evidence points to the role of sympathetic nervous system stimulation and activation of the renin-angiotensin and aldosterone system as a contributor to progressive right heart failure.
The study will determine if treatment with spironolactone is associated with reduction in right ventricular wall stress. In addition, the study aims to evaluate the effects of spironolactone on cardiac sympathetic activity assessed by HED(11 C-hydroxy-ephedrine) retention on PET(positron emission tomography) imaging, and global autonomic function assessed by heart rate variability.
Approximately 30 patients with RHF will be randomized to receive either spironolactone daily or placebo.
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)
盲法说明
Patients will be blinded to study treatment for the duration of the study. Clinicians will also be blinded to study drug assignment. Evaluation of all study results will be done blinded to treatment randomization. Because of the double-blind design, safety laboratory tests, and monitoring of potential side effects will be performed for each participant for the duration of the trial, regardless of the treatment arm.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide a personally signed and dated inform consent form.
- •Male or female ≥ 18 years.
- •Able to comply with all study procedures.
- •History of right heart failure (RHF) secondary to either:
- •i) WHO, group 1 pulmonary arterial hypertension PAH OR ii) WHO group II PH with normal LV systolic function OR iii) WHO group III or IV PH OR iv) primary RV cardiomyopathy.
- •Current NYHA II-IV
- •RV dysfunction as measured by 2D echocardiogram:
- •i)defined as a tricuspid annular plane systolic excursion (TAPSE) <16 mm ii) and /or a two dimensional fractional area change <35% on screening echo plus
- •NT-proBNP>400 pg/ml
- •Chronic use of diuretics
- •Clinical stability: defined as no need for increased diuretics, hospitalization or emergency room visit 3 months prior to enrollment
排除标准
- •Patients on chronic MRA therapy or other potassium sparing diuretics.
- •Baseline serum potassium>5 ummol/l.
- •Estimated glomerular filtration rate <30 ml/min.
- •LV ejection fraction <45%,
- •Moderate or severe LV diastolic function,
- •Moderate or severe aortic or valvular disease.
- •Patients requiring augmentation of diuretics or otherwise not meeting definition for clinical stability.
- •Severe Liver Failure (Child-Pugh Class C)
- •Claustrophobia or inability lie still in a supine position
- •Patients with contraindications to either PET or CMR imaging
- •Pregnancy or lactation.
- •Unable to provide consent and comply with follow up visits.
研究组 & 干预措施
Placebo
Participants with chronic right-sided heart failure will receive placebo daily for a total duration of 12 weeks.
干预措施: Placebo (Drug)
Spironolactone
Participants with chronic right-sided heart failure will receive spironolactone 12.5mg daily up to a maximum dose of 50 mg daily for a total duration of 12 weeks.
干预措施: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82 (Radiation)
Placebo
Participants with chronic right-sided heart failure will receive placebo daily for a total duration of 12 weeks.
干预措施: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82 (Radiation)
Spironolactone
Participants with chronic right-sided heart failure will receive spironolactone 12.5mg daily up to a maximum dose of 50 mg daily for a total duration of 12 weeks.
干预措施: Cardiac MRI (Gadolinium enhanced) (Diagnostic Test)
Placebo
Participants with chronic right-sided heart failure will receive placebo daily for a total duration of 12 weeks.
干预措施: Cardiac MRI (Gadolinium enhanced) (Diagnostic Test)
Spironolactone
Participants with chronic right-sided heart failure will receive spironolactone 12.5mg daily up to a maximum dose of 50 mg daily for a total duration of 12 weeks.
干预措施: Spironolactone (Drug)
结局指标
主要结局
Change in Ventricular Wall Stress
时间窗: Baseline and 12 weeks
To determine if treatment with spironolactone is associated with a significant reduction in RV ventricular wall stress, as reflected by a reduction in serum NT-proBNP, in patients with chronic stable right HF when compared to placebo.
次要结局
- Change in Cardiac Sympathetic Nervous System Activity(Baseline to 12 weeks)
- Change in Biomarkers of Fibrosis(Baseline to 12 weeks)
- Change in Systemic Sympathetic Activation(Baseline to 12 weeks)
- Change in Cardiac Autonomic Nervous System Function(Baseline to 12 weeks)
- Change in Right Ventricle Function(Baseline to 12 weeks)
- Change in Right Ventricle areas of fibrosis(Baseline to 12 weeks)
- Change in Right Ventricle Structure(Baseline to 12 weeks)
- Number of participants with treatment-related adverse events.(number of adverse events from baseline to 12 weeks.)