NCT05411991

Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 107 (actual)
• Sponsor: Vrije Universiteit Brussel · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.

Detailed description

Key interventions are: * Assessment of UNa in spot urine samples after every bolus administration of loop diuretics with continuation of intravenous diuretics until resolution of clinical signs of fluid overload AND UNa \<80 mmol/L * Dosing of loop diuretic bolus according to estimated glomerular filtration rate (eGFR) * Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia (\>145 mmol/L) or metabolic acidosis (bicarbonate \<22 mmol/L) * Upfront use of oral chlorthalidone 50 mg OD if eGFR \<30 mL/min/1.73m² OR hypernatremia (\>145 mmol/L) * Switch to full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa \<80 mmol/L and persistent clinical signs of fluid overload * Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during diuretic therapy with intravenous diuretics

Conditions

• Acute Heart Failure
• Diuretics Drug Reactions

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	UNa measurement after intravenous loop diuretic bolus	Sodium concentration is measured on a urine spot sample, collected 30-120 min after administration of every protocol-specified intravenous bumetanide dose.
DRUG	Intravenous acetazolamide 500 mg OD	Upfront use of intravenous acetazolamide 500 mg OD as part of the diuretic treatment, unless hypernatremia (\>145 mmol/L) or metabolic acidosis (bicarbonate \<22 mmol/L) is present at the moment of the scheduled administration.
DRUG	Intravenous bumetanide TID	An intravenous bolus of bumetanide is administered TID, with dosing according to eGFR: 2 mg for an eGFR \>45 mL/min/1.73m²; 3 mg for an eGFR 30-45 mL/min/1.73m²; and 4 mg for an eGFR \<30 mL/min/1.73m². At any time diuretic resistance is encountered (persistent clinical signs of fluid overload with UNa \<80 mmol/L), a dose of 4 mg TID is used.
DRUG	Oral chlorthalidone OD	In case of hypernatremia (\>145 mmol/L) or low eGFR (\<30 mL/min/1.73m²), oral chlorthalidone 50 mg OD is added to the diuretic treatment. At any time diuretic resistance is encountered (persistent clinical signs of fluid overload with UNa \<80 mmol/L), oral chlorthalidone is provided at a dose of 100 mg OD. Chlorthalidone is never administered in case of hypotonic hyponatremia with serum sodium concentration \<135 mmol/L.
DRUG	Intravenous canrenoate 200 mg OD	At any time diuretic resistance is encountered (persistent clinical signs of fluid overload with UNa \<80 mmol/L), intravenous canrenoate 200 mg OD is provided. Canrenoate is never administered in case of hypotonic hyponatremia with serum sodium concentration \<135 mmol/L or if serum potassium levels are \>5.5 mmol/L. If canrenoate is administered, oral mineralocorticoid receptor drugs are temporarily withhold until switch to oral diuretic treatment.
OTHER	Maintenance infusion	A maintenance infusion with 500 mL dextrose 5% and 3 g MgSO4 is started at an infusion rate of 20 mL/h upon the moment of first protocol-specified administration of intravenous diuretics and continued until switch to oral diuretic therapy. 40 mmol KCl is added if serum potassium levels are \<4 mmol/L. In case of hypotonic hyponatremia with serum sodium concentration \<130 mmol/L, dextrose 5% will not be provided and MgSO4 will be administered in 50 mL of normal saline (NaCl 0.9%).
DRUG	Oral potassium supplements	If serum potassium levels are \<3.5 mmol/L at any time during the administration of intravenous diuretics, oral potassium supplements are provided as needed to keep serum potassium levels \>4 mmol/L
OTHER	Intravenous hypertonic saline	In case of hypotonic hyponatremia with serum sodium concentration \<125 mmol/L, a bolus of 150 mL hypertonic saline 3% is administered and repeated OD if necessary, until sodium levels are ≥135 mmol/L.
OTHER	Switch to oral diuretic therapy	Upon complete resolution of clinical signs of fluid overload with UNa \<80 mmol/L, intravenous diuretics are switched to an oral schedule including: * Loop diuretics with dose \& frequency at the discretion of the treating physician * Chlorthalidone 50 mg if added for diuretic resistance at any time during the intravenous diuretic phase * Spironolactone 25 mg or another equivalent mineralocorticoid receptor antagonist
OTHER	Usual AHF care	It is recommended to administer an intravenous loop diuretic dose at least BID (or through continuous infusion), with the aim of achieving a urine output 3-5 L per day until the patient is considered in an optimal volume status as is recommended by current guidelines.

Timeline

• Start date: 2022-06-12
• Primary completion: 2024-07-01
• Completion: 2024-07-01
• First posted: 2022-06-09
• Last updated: 2025-08-08
• Results posted: 2025-08-08

Locations

2 sites across 1 country: Belgium