Diamox/Aldactone to Increase the URinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Acetazolamide Arm: Natriuresis 24 h
研究概览
简要总结
This study has two primary objectives:
- To compare combination therapy with acetazolamide and low-dose loop diuretics versus high-dose loop diuretics (standard of care) in patients with acute decompensated heart failure at high risk for diuretic resistance.
- To demonstrate the safety and efficacy of upfront therapy with spironolactone in addition to loop diuretic therapy in patients with acute decompensated heart failure at high risk for diuretic resistance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (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
- •Older than 18 years and able to give informed consent
- •Clinical diagnosis of acute decompensated heart failure within the previous 8 h
- •At least two clinical signs of congestion (edema, ascites, jugular venous distension, or pulmonary vascular congestion on chest radiography)
- •Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide (1 mg bumetanide = 40 mg furosemide = 20 mg torsemide) for at least 1 month before hospital admission
- •NT-proBNP >1000 ng/L
- •Left ventricular ejection fraction <50%
- •At least one out of three of the following criteria:
- •Serum sodium <136 mmol/L
- •Serum urea/creatinine ratio >50 (comparable to a BUN/creatinine ratio >25)
- •Admission serum creatinine increased with >0.3 mg/dL compared to previous value within 3 months before admission
排除标准
- •History of cardiac transplantation and/or ventricular assist device
- •Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain and/or electrocardiographic changes in addition to a troponin rise >99th percentile
- •Mean arterial blood pressure <65 mmHg, or systolic blood pressure <90 mmHg at the moment of admission
- •Use of intravenous inotropes, vasopressors or nitroprusside at any time point during the study
- •A baseline estimated glomerular filtration rate <15 mL/min/1.73m² according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at the moment of inclusion
- •Use of renal replacement therapy or ultrafiltration before study inclusion
- •Treatment with acetazolamide within the previous month
- •Treatment with ≥2 mg bumetanide or an equivalent dose during the index hospitalization before randomization
- •Use of diuretics, vasopressin antagonists or mineralocorticoid receptor antagonist not specified by the protocol
- •Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within 3 days
研究组 & 干预措施
High-dose loop diuretics, upfront spironolactone
2x2 factorial design: This group is the experimental group for the study intervention with upfront spironolactone. This group receives high-dose loop diuretics as an active comparator to the study intervention with acetazolamide.
See interventions for more details.
干预措施: High-dose loop diuretics (Drug)
High-dose loop diuretics, no spironolactone
2x2 factorial design: This group receives high-dose loop diuretics as an active comparator to the study intervention with acetazolamide. This group receives no intervention with regards to the spironolactone arm.
See interventions for more details.
干预措施: High-dose loop diuretics (Drug)
Acetazolamide/low-dose loop diuretics, no spironolactone
2x2 factorial design: This group is the experimental group for the study intervention with acetazolamide. This group receives no intervention with regards to the spironolactone arm.
See interventions for more details.
干预措施: Combination therapy with acetazolamide and low-dose loop diuretics (Drug)
High-dose loop diuretics, upfront spironolactone
2x2 factorial design: This group is the experimental group for the study intervention with upfront spironolactone. This group receives high-dose loop diuretics as an active comparator to the study intervention with acetazolamide.
See interventions for more details.
干预措施: Upfront therapy with oral spironolactone (Drug)
Acetazolamide/low-dose loop diuretics, upfront spironolactone
2x2 factorial design: This group is the experimental group for both study interventions (acetazolamide and upfront spironolactone).
See interventions for more details.
干预措施: Upfront therapy with oral spironolactone (Drug)
Acetazolamide/low-dose loop diuretics, upfront spironolactone
2x2 factorial design: This group is the experimental group for both study interventions (acetazolamide and upfront spironolactone).
See interventions for more details.
干预措施: Combination therapy with acetazolamide and low-dose loop diuretics (Drug)
结局指标
主要结局
Acetazolamide Arm: Natriuresis 24 h
时间窗: 24h
For the acetazolamide arm of the study, the primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 h after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). Subsequently, patients receiving acetazolamide and low-dose loop diuretics (both the groups with and without upfront spironolactone together) are compared to patients not receiving acetazolamide but high-dose loop diuretics instead (both the groups with or without upfront spironolactone together)
Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L)
时间窗: 72h
For the spironolactone arm of the study, the primary end-point is the incidence of either hypo- (serum potassium \<3.5 mmol/L) or hyperkalemia (serum potassium \>5.0 mmol/L) at any of 3 morning blood samples at consecutive days after randomization. Patients receiving upfront spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy) are compared with them receiving no spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy).
次要结局
- NT-proBNP Change After 72 h(72h)
- Number of Participants With Worsening Renal Function(72h)
- Persistent Renal Impairment(4 weeks after hospital discharge)
- Peak Plasma Aldosterone Concentration After 72 h(72h)
- Peak Plasma Renin Activity After 72 h(72h)
研究者
Wilfried Mullens, MD PhD
Prof. Dr.
Ziekenhuis Oost-Limburg