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

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.

Conditions

• Acute Heart Failure
• Diuretics Drug Reactions

Interventions

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.

Sponsors & Collaborators

• Roche Diagnostics GmbH

  collaborator INDUSTRY

• Jessa Hospital

  collaborator OTHER

• Vrije Universiteit Brussel

  lead OTHER

Principal Investigators

• Frederik H Verbrugge, M.D.; Ph.D.; M.Sc. · Vrije Universiteit Brussel

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-12

Primary Completion

2024-07-01

Completion

2024-07-01

Countries

• Belgium

Study Locations