Acetazolamide as a Diuretic in patients Admitted with Heart Failure: a pilot and exploratory study (ADA-HF)

Project Description

Acetazolamide as a chloride sparing Diuretic in patients Admitted with Heart Failure: a pilot and exploratory study (ADA-HF)

Background
High dose intravenous (IV) loop diuretics are the cornerstone of treatment for venous congestion in patients admitted with heart failure (HF). If a patient fails to respond to initial treatment, thiazide or thiazide-like diuretics are often introduced, but the evidence to support their use is scant and inconsistent. A related issue is the high rate of electrolyte abnormalities with loop and thiazide diuretics; hypochloraemia is common and may drive adverse outcome. The Acetazolamide as a Diuretic in patients Admitted with Heart Failure (ADA-HF) study aims to investigate the effect of the carbonic anhydrase inhibitor acetazolamide on diuresis, congestion, and serum chloride concentrations in patients admitted to hospital with HF.

Methods and Results
ADA-HF is an open-label, randomised, controlled pilot study in Hull, UK. We aim to recruit a minimum of 40 patients admitted to hospital with severe venous congestion due to HF and who are deemed to require 24 hour IV furosemide infusion at 10 mg/hr (standard of care). Patients will be randomly assigned to either standard of care or standard of care plus oral acetazolamide 250mg twice daily. The co-primary endpoints will be 1) the difference in daily net fluid loss (total intake volume – total urinary volume) over a four day period; 2) the difference in serum chloride concentrations between day 1 and day 4, with multiple exploratory secondary endpoints including changes in ultrasound markers of venous congestion, and feasibility of recruitment. Safety endpoints include the rates of hypotension, hyponatraemia, hyperchloraemia and side effects of acetazolamide. The recruitment target will provide 80% power and 5% two-tailed significance to detect a 500ml difference in daily net fluid loss, and a 2.4 mmol/L difference in serum chloride concentrations between day 1 and day 4 between the groups.

Conclusion
The results of the ADA-HF pilot study will be used to inform a large trial of acetazolamide for the prevention and treatment of hypochloraemia in patients admitted with HF and its effect on hard endpoints.