Phase 4
Completed N=34
Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure
Source: ClinicalTrials.gov NCT01973335 ↗Enrolled (actual)
34
Serious AEs
38.2%
Results posted
Mar 2019
Primary outcomePrimary: Acetazolamide Arm: Natriuresis 24 h — 324; 300; 211; 190 mmol — p=0.515
◆ Published Evidence
Highly cited
118citations · ~17 / year
Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance.
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.
Linked Publications (2)
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Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance.
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Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Acetazolamide Arm: Natriuresis 24 h |
324; 300; 211; 190 | 0.515 |
| PRIMARY Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L) |
1; 2; 5; 2 | 0.270 |
| SECONDARY NT-proBNP Change After 72 h |
-20; -11; -3; -6 | — |
| SECONDARY Number of Participants With Worsening Renal Function |
2; 0; 3; 0 | — |
| SECONDARY Persistent Renal Impairment |
3; 1; 0; 1 | — |
| SECONDARY Peak Plasma Aldosterone Concentration After 72 h |
196; 234; 302; 204 | — |
| SECONDARY Peak Plasma Renin Activity After 72 h |
3.8; 5.0; 12.0; 2.5 | — |
Eligibility 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 (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
Data sourced from ClinicalTrials.gov (NCT01973335) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.