Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure (DIURESIS-CHF)

Hasselt University

Status and phase: Completed; Phase 4

Conditions: Heart Failure

Treatments: Drug: High-dose loop diuretics; Drug: Upfront therapy with oral spironolactone; Drug: Combination therapy with acetazolamide and low-dose loop diuretics

Study type: Interventional

Funder types: Other

Identifiers

NCT01973335

ZOL-DIURESIS-CHF

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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34 participants in 4 patient groups

Acetazolamide/low-dose loop diuretics, upfront spironolactone

Experimental group

Description:

2x2 factorial design: This group is the experimental group for both study interventions (acetazolamide and upfront spironolactone). See interventions for more details.

Treatment:

Drug: Upfront therapy with oral spironolactone

Drug: Combination therapy with acetazolamide and low-dose loop diuretics

High-dose loop diuretics, upfront spironolactone

Experimental group

Description:

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.

Treatment:

Drug: High-dose loop diuretics

Drug: Upfront therapy with oral spironolactone

Acetazolamide/low-dose loop diuretics, no spironolactone

Experimental group

Description:

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.

Treatment:

Drug: Combination therapy with acetazolamide and low-dose loop diuretics

High-dose loop diuretics, no spironolactone

Active Comparator group

Description:

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.

Treatment:

Drug: High-dose loop diuretics