Furosemide With Early Sequential Nephron Blockade Versus Furosemide Alone in Acute Heart Failure Patients With Furosemide-guided Diuretic Resistance: A Double-blinded, Randomized, Placebo-controlled Study
试验速览
- 阶段
- 3 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Urine volume
研究概览
简要总结
This study aims to demonstrate the efficacy of sequential nephron blockade by adding hydrochlorothiazide or spironolactone on intravenous furosemide compared to intravenous furosemide alone in the treatments of volume overload in patients with acute heart failure who have diuretic resistance from furosemide stress test.
详细描述
This study is a randomised, double-blinded, double-dummy, placebo-controlled study to demonstrate the efficacy of oral hydrochlorothiazide or spironolactone in combination with intravenous furosemide compared to intravenous furosemide in combination with placebo. Dosage of intravenous furosemide will be adjusted according to pre-defined protocol. The primary outcome is urine volume during 72 hours after randomisation.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosis of acute heart failure which is defined by 2 of the 3 following features: ≥2+ leg edema, jugular venous pressure >10 cm from physical examination or central venous pressure >10 mmHg, and bilateral pulmonary edema or bilateral pleural effusion from chest radiography
- •Patients consent to participate into the study
排除标准
- •Patients who receive furosemide ≥500 mg/day or hydrochlorothiazide ≥100 mg/day or spironolactone ≥100 mg/day or tolvaptan of any doses
- •Patients who have systolic blood pressure <100 mmHg or who need vasoactive drugs inotropic agents (except dobutamine)
- •Patients with intravascular volume depletion from clinical evaluation
- •Patients with chronic kidney disease stage 5 (estimated glomerular filtration rate <15 ml/min/1.73 m2) or patients who receive maintenance dialysis
- •Patients who require renal replacement therapy at the time of admission
- •Patients whom diagnosed hypertrophic obstructive cardiomyopathy, severe valvular stenosis or complex congenital heart disease
- •Patients with sepsis or systemic infection
- •Pregnant women
- •Patients who have history of furosemide, spironolactone or hydrochlorothiazide allergy
研究组 & 干预措施
Furosemide with spironolactone or hydrochlorothiazide
IV furosemide dosage will be adjusted according to the protocol as follows. Level 1: previous oral furosemide dose ≤80 mg/day; furosemide 80 mg IV bolus every 6 hours Level 2: previous oral furosemide dose 81-160 mg/day; furosemide 160 mg IV bolus every 6 hours Level 3: previous oral furosemide dose >160 mg/day; furosemide 250 mg IV bolus every 6 hours Furosemide dosage will be adjusted to keep urine output between 3,000 and 5,000 ml/day and >600 ml during 6 hours after furosemide administration.
If the urine output <3,000 ml/day or <600 ml per 6 hours, furosemide dosage will be increase 1-level up per protocol above.
If the urine output >5,000 ml/day, furosemide dosage will be reduced 1-level down per protocol above.
Patients will be received spironolactone or hydrochlorothiazide in combination with intravenous furosemide according to patients' serum potassium levels.
干预措施: Spironolactone or hydrochlorothiazide (Drug)
Furosemide with placebo
IV furosemide dosage will be adjusted according to the pre-defined protocol as shown in the experimental group.
Patients will be received spironolactone placebo or hydrochlorothiazide placebo in combination with intravenous furosemide according to patients' serum potassium levels.
干预措施: Placebo (Drug)
结局指标
主要结局
Urine volume
时间窗: 72 hours
Total urine volume after randomisation
次要结局
- Urine volume(24 and 48 hours)
- Body weight(72 hours after randomisation)
- Length of hospital admission(During hospital admission period)
- Furosemide dose(72 hours after randomisation)
- Levels of B-type atrial natriuretic peptide (BNP)(72 hours and 7 days after randomisation)
- Number of participants with adverse events(During hospital admission)
- Dyspnea score assessed by visual analogue scale(At randomization, and 6, 12, 24, 48 and 72 hours after randomization)
研究者
Kajohnsak Noppakun
Assistant Professor of Medicine
Chiang Mai University