Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Daily urine output
研究概览
简要总结
This is a prospective, single-center, open-label and randomized trial for evaluation of the effect of a 5-day administration of high doses of spironolactone (≥100mg daily) on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with acute decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of care (SOC) in management of heart failure (HF) patients. However, recommended doses of MRAs (up to 50mg daily) have any impact on signs and symptoms of volume overload. Therefore, the proposed study will aim to show the impact of high doses of spironolactone to improve diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.
详细描述
Congestion represents a hallmark feature of ADHF, which is present in more than 90% of patients hospitalized for this diagnosis. Intravenous loop diuretics are the mainstay of treatment. Nonetheless, nearly half of the patients who are hospitalized for AdHF continue to have residual symptoms and sign of congestion at time of discharge. Various pharmacological and non-pharmacological interventions have been proposed over the past years as potential means for relieving congestion in hospitalized ADHF patients. However, their efficacy has not been shown.
Given that hyperaldosteronism is a key feature in HF, the hypothesis that administration of high doses of spironolactone can potentiate the natriuretic effects of loop diuretics and relieve congestion in the setting of ADHF has been raised.
According to the most recent guidelines spironolactone can be considered in combination with loop diuretic in patients with resistant edema or insufficient symptomatic response. However, spironolactone at a dose of 100 mg daily has failed to increase diuresis in patients with ADHF.
The present study will assess the effect of high per os doses of spironolactone (≥100mg) on top of SOC treatment compared with SOC treatment alone on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.
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
- None
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
- •Diagnosis of acute heart failure within the past 8 hours
- •Two of the following:
- •jugular vein distention,
- •pulmonary congestion
- •NT-proBNP >1,000 pg/ml or >3,000 pg/ml (in the presence of atrial fibrillation)
- •Per os mean daily loop diuretic dose equivalent to 80 mg of furosemide for at least 1 month prior to presentation and at least one of the following:
- •serum urea/serum creatinine > 50 at presentation,
- •serum creatinine increased >0.3 mg/dl compared with previous value (within the last year),
- •serum creatinine > 1.8 mg/dl.
排除标准
- •pregnancy or breast feeding
- •current acute coronary syndrome
- •significant valvular disease
- •pulmonary embolism
- •allergy or intolerance to spironolactone
- •current mechanical circulatory support
- •primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy
- •mean arterial pressure <65mmHg or systolic arterial pressure <90 mmHg at presentation
- •anticipated use of inotropes or vasodilators (other than renal doses of dopamine, i.e. <2.5 μg/kg/min)
- •anticipated need of ultrafiltration
- •exposure to nephrotoxic agents within 3 days of presentation
- •serum potassium> 5 mmol/L
- •per os receipt of spironolactone or eplerenone in a dose > 50 mg daily prior to presentation.
研究组 & 干预措施
High-dose spironolactone
Participants in this arm will receive high doses of per os spironolactone, defined as doses ≥100 mg daily, on top of standard of care treatment for acute heart failure
干预措施: Spironolactone (Drug)
结局指标
主要结局
Daily urine output
时间窗: 5 days
Urine output in liters per 24 hours will be tracked from enrollment to day 5.
次要结局
- Total urine output(5 days)
- Total weight change(5 days)
- Changes in natriuresis between days 1, 3 and 5(5 days)
- Daily weight change(5 days)
- Natriuresis on days 1, 3 and 5(5 days)
- Changes in NT-proBNP between days 1 and 5(5 days)
研究者
Chris Kapelios
Cardiology Fellow
Laikο General Hospital, Athens