Tolvaptan add-on Therapy to Overcome Loop Diuretic Resistance in Acute Heart Failure With Renal Dysfunction
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- Cumulative urine volume output at 48h after randomization
研究概览
简要总结
Renal dysfunction, which comprises 10%-40% of acute heart failure patients (AHF), plays an important role in diuretic resistance mechanism. DR-AHF was designed to demonstrate the effectiveness of early tolvaptan (a vasopressin-2 receptor antagonist) add-on therapy in acute heart failure patients with renal dysfunction and clinical evidence of loop diuretic resistance.
详细描述
This is a single-center, open-label, randomized controlled trial, which will enroll 128 patients hospitalized due to AHF. These patients with wet-warm phenotype whose estimated glomerular filtration rates at admission are above 15 and below 60 mL/min/1.73 m2, and cumulative urine output <300 mL in 2 hours after the first dose of intravenous furosemide will be randomly assigned 1:1 to receive a standard care with uptitrating intravenous furosemide alone or a combination therapy with tolvaptan 15mg once daily for 2 days. The standard furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association. The primary endpoint is the cumulative urine output at 48 hour. Key secondary endpoints include the improvement of fractional excretion of sodium at 6 hour, the total dose of furosemide, the changes in the body weights, the net fluid loss, the lessening of diastolic dysfunction parameters on echocardiography, and the incidence of clinically relevant worsening renal function at 48 hour.
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
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Admitted to hospital with a primary diagnosis of acute heart failure with wet-warm phenotype
- •Cumulative urine volume output < 300ml within 2 hours after the first dose of intravenous furosemide
- •eGFR at admission 15-60ml/min/1.73m2
排除标准
- •Acute coronary syndrome
- •Consciousness impairment
- •Pregnant or breastfeeding women
- •Severe valvular heart diseases (severe valvular stenosis or regurgitation)
- •Admission sodium level > 140 mEq/L
- •Serum total bilirubin > 3 mg/dL
- •Serum potassium > 5.5 mmol/L
- •Allergy or contraindication for tolvaptan
- •Emergency indication for hemodialysis
- •Cardiogenic shock or mechanical circulation support
研究组 & 干预措施
Conventional diuretic group
The conventional furosemide treatment will follow the modified 2019 Position Statement from the ESC Heart Failure Association
干预措施: Tolvaptan 15 MG (Drug)
Vasopressin-2 antagonist group
Tolvaptan 15mg once daily for 2 days will be added-on the furosemide strategy based on the modified 2019 Position Statement from the ESC Heart Failure Association
干预措施: Tolvaptan 15 MG (Drug)
结局指标
主要结局
Cumulative urine volume output at 48h after randomization
时间窗: Hour 48
Urine volume in mL
次要结局
- Cumulative dose of furosemide at 48h after randomization(Hour 48)
- Symptom of dyspnea by 7-point Likert scale at 24h and 48h after randomization(Hour 24, Hour 48)
- Changes in body weight at 24h and 48h after randomization(Hour 24, Hour 48)
- Incidence of clinically relevant worsening renal function at 24h and 48h after randomization(Hour 24, Hour 48)
- Changes in serum electrolytes measured at 12h, 24h and 48h after randomization(Hour 12, Hour 24, Hour 48)
- Changes in urine electrolyte excretion at 6h, 24h and 48h(Hour 6, Hour 24, Hour 48)
- Changes in NT-proBNP at 48h after randomization(Hour 0, Hour 48)
- Changes in mitral e' on echocardiography(Hour 24, Hour 48)
- Changes in E/e' ratio on echocardiography(Hour 24, Hour 48)
- Changes in left atrial volume on echocardiography(Hour 24, Hour 48)
- Changes in tricuspid regurgitation maximal velocity on echocardiography(Hour 24, Hour 48)
- Changes in inferior vena cava maximal diameter on echocardiography(Hour 24, Hour 48)