Infusion of Furosemide to Improve Diuretic Efficiency in Acute Heart Failure

INFUSE-AHF is an investigator-initiated, multicentre, open-label, pragmatic, randomized clinical trial conducted at hospitals in Denmark. The trial compares two commonly used ways of administering intravenous furosemide in adults hospitalized with acute heart failure and volume overload: Continuous infusion preceded by a loading dose, and bolus injections administered three times a day.

The rationale for the trial is that intravenous loop diuretics are standard treatment for acute heart failure with volume overload, but the optimal method of administration remains uncertain. Previous evidence has not established whether continuous infusion or bolus injections are superior. In addition, continuous infusion without an initial loading dose may delay achievement of effective plasma concentrations. The INFUSE-AHF trial, therefore, specifically evaluates continuous infusion preceded by a loading dose compared with bolus injections three times a day.

The trial includes three phases. The inclusion phase starts when a potential participant is identified during hospitalization and ends when the first dose of trial treatment is administered. The treatment phase starts with the first administration of intravenous furosemide and continues until the last weight measurement on the morning of Day 4. The follow-up phase starts after the treatment phase and continues until 30 days after the first injection.

Participants are randomized in a 1:1 ratio to one of the two treatment strategies. In the continuous infusion group, an initial loading dose is administered immediately before the infusion is started. In the bolus group, furosemide is administered as bolus injections three times a day, and the first bolus includes an additional dose to mirror the loading dose strategy. Daily intravenous furosemide doses are determined according to the participant's oral loop diuretic dose at admission using a predefined dosing algorithm. During the first part of the treatment period, doses are protocolized. On the morning of Day 3, the treating clinician may increase the dose, maintain the same dose, or stop intravenous treatment according to the protocol and the participant's clinical status.

Approximately 436 participants will be enrolled. The primary endpoint is net weight loss 3 days, equivalent to approximately 72 hours, after randomization. Secondary endpoints include net weight loss 2 days after randomization, change in dyspnea on a Visual Analog Scale 3 days after randomization, days alive out of hospital to Day 30, and length of hospital stay. Safety endpoints include acute kidney injury, severe electrolyte disturbances, incidents, and side effects.

Inclusion criteria

• Clinical diagnosis of acute heart failure with volume overload
• At least 1 sign of volume overload
• Anticipated intravenous furosemide treatment for at least 3 days
• Age 18 years or older

Exclusion criteria

• Shock
• Patient requiring treatment with inotropes or vasopressors
• Current or planned use of renal replacement therapy or ultrafiltration
• Patient with a renal transplant
• Patients who are pregnant or breastfeeding
• Severe hypokalaemia, defined as potassium less than 2.5 mmol/L, or severe hyponatremia, defined as sodium less than 125 mmol/L
• Allergy to furosemide and its components