Rationale and design of the acetazolamide as a chloride sparing diuretic in patients admitted with heart failure (ADA-HF) trial.

Aims: The Acetazolamide as a chloride-sparing Diuretic in patients Admitted with Heart Failure (ADA-HF) trial will assess the safety and diuretic effect of oral ACZ given alongside a high-dose IV loop diuretic in patients admitted to the hospital with heart failure (HF) and severe fluid retention. Hypochloraemia is common in patients with HF and is associated with worse outcomes, but there are few treatment options available: we will also assess whether ACZ reduces urine chloride loss. Methods and results: The ADA-HF trial is a single centre, open-label, randomized-controlled trial of ACZ 250 mg twice daily plus standard care vs. standard care alone. The trial duration is 4 days. We will recruit 50 patients with severe peripheral oedema due to HF requiring standard care (240 mg of IV furosemide per day given via continuous infusion at 10 mg per hour). The co-primary endpoints are (1) the difference in net fluid loss daily, and over 4 days; and (2) difference in serum chloride concentrations between baseline and day 4. The trial has 80% power to detect a difference in fluid balance of 500-1000 mL per day; and a difference in serum chloride concentration of 1 mmol/L per day. Secondary endpoints include but are not limited to: time to recruit per patient; rate of adverse events; rate of recruitment; and cause-specific rate of drop-out of the study. Conclusion: ACZ may be a useful adjunct to diuretic therapy, but the safety and diuretic efficacy of oral ACZ when used alongside high-dose loop diuretics is unknown. ADA-HF will complement the ADVOR trial and may clarify what role ACZ may have for patients with severe congestion. Trial registration: ISRCTN registry. ISRCTN13060336. Registered on 09/02/2023. URL: https://doi.org/10.1186/ISRCTN13060336.