Acetazolamide and Spironolactone to Increase Natriuresis in Congestive Heart Failure
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.
Timeline
- Start
- 2013-11
- Primary completion
- 2017-04
- Completion
- 2017-10
Outcome
Missed primary endpoint
registry p = 0.515; Mean Difference (Final Values) 30 (95% CI -63 to 123) NCT01973335 ↗
paper Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm (264 ± 126 vs. 234 ± 133 mmol; P = 0.515). PMID 31074184 ↗
registry p = 0.270; Risk Difference (RD) -0.2; Fisher Exact NCT01973335 ↗
paper hyperkalaemia: 6% vs. 11%; hypokalaemia: 13% vs. 28%, respectively; p-value = .270). PMID 29587582 ↗
Publications
- Results Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogne W, Mullens W. Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome. Acta Cardiol. 2019 Apr;74(2):100-107. doi: 10.1080/00015385.2018.1455947. Epub 2018 Mar 27.
- Results Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogne W, Mullens W. Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance. Eur J Heart Fail. 2019 Nov;21(11):1415-1422. doi: 10.1002/ejhf.1478. Epub 2019 May 9.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Acetazolamide | Small molecule | 250 mg | Intravenous |
| Subject | Bumetanide | Small molecule | 1 mg | Intravenous |
| Subject | Spironolactone | Small molecule | 25 mg | Oral |