Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure

• Status: Completed
• Trial end date: 2017-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This study has two primary objectives:

1. 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.

2. 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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hasselt University
• Collaborators: Universitaire Ziekenhuizen Leuven; University Hospital Leuven, Leuven, Belgium; Ziekenhuis Oost-Limburg
• Treatments: Acetazolamide; Bumetanide; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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