Infusion of Furosemide to Improve Diuretic Efficiency in Acute Heart Failure (INFUSE-AHF)

Infusion of Furosemide to Improve Diuretic Efficiency in Acute Heart Failure (INFUSE-AHF)

Acute heart failure is a condition where the heart suddenly cannot pump blood well enough for the body's needs. Many people admitted to the hospital with acute heart failure have too much fluid in the body. This can cause shortness of breath, swelling, and the need for treatment with water-removing medicine.

Furosemide is a commonly used water-removing medicine that is given into a vein to treat fluid overload. It can be given in different ways. One way is as a continuous infusion, where the medicine is given slowly over time through a pump. Another way is as repeated injections given several times a day. It is not known whether one of these ways is better than the other for removing excess fluid in people with acute heart failure.

The purpose of this study is to compare two ways of giving furosemide into a vein: Continuous infusion started with an initial extra dose, and bolus injections given three times a day. About 436 adults admitted to hospitals in Denmark with acute heart failure and fluid overload will take part. Participants will be randomly assigned to one of the two treatment groups. This means that chance will decide which treatment method each participant receives.

The main thing the researchers will measure is how much body weight participants lose about 3 days after randomization. Weight loss is used as a measure of how much excess fluid has been removed.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Heart Failure; Volume Overload
• Intervention / Treatment: Drug: Intravenous furosemide continuous infusion; Drug: Intravenous furosemide bolus injections

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 436
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Esben Merrild, MD; Phone Number: +4522996026; Email: esbenmerrild@clin.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous infusion preceded by a loading dose; Participants receive intravenous furosemide administered as a continuous infusion preceded by an initial loading dose. The loading dose is administered immediately before initiation of the infusion. Daily intravenous furosemide doses are determined according to the participant's oral loop diuretic dose at hospital admission using a predefined dosing algorithm.	Drug: Intravenous furosemide continuous infusion; Intravenous furosemide administered as a continuous infusion preceded by a loading dose. Daily intravenous furosemide doses are determined according to the participant's oral loop diuretic dose at hospital admission using a predefined dosing algorithm.; Other Names: Furosemide infusion
Experimental: Bolus injections three times a day; Participants receive intravenous furosemide administered as bolus injections three times a day. The first bolus injection includes an additional dose to mirror the loading dose strategy used in the continuous infusion group. Daily intravenous furosemide doses are determined according to the participant's oral loop diuretic dose at hospital admission using a predefined dosing algorithm.	Drug: Intravenous furosemide bolus injections; Intravenous furosemide administered as bolus injections three times a day. The first bolus injection includes an additional dose to mirror the loading dose strategy used in the continuous infusion group. Daily intravenous furosemide doses are determined according to the participant's oral loop diuretic dose at hospital admission using a predefined dosing algorithm.; Other Names: Furosemide bolus injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net weight loss 3 days after randomization	Net change in body weight from randomization to the morning of Day 4, corresponding to approximately 72 hours after randomization.	From randomization to approximately 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net weight loss 2 days after randomization	Net change in body weight from randomization to the morning of Day 3, corresponding to approximately 48 hours after randomization.	From randomization to approximately 48 hours
Change in dyspnea 3 days after randomization	Change in dyspnea assessed using a Visual Analogue Scale from randomization to the morning of Day 4, corresponding to approximately 72 hours after randomization.	From randomization to approximately 72 hours
Days alive out of hospital to Day 30	Number of days alive and out of hospital from randomization to Day 30.	From randomization to 30 days
Length of hospital stay	Duration of the index hospital admission.	From randomization up to 30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net weight loss 1 day after randomization	Net change in body weight from randomization to the morning of Day 2, corresponding to approximately 24 hours after randomization.	From randomization to approximately 24 hours
Change in dyspnea 1 day after randomization	Change in dyspnea assessed using a Visual Analogue Scale from randomization to the morning of Day 2, corresponding to approximately 24 hours after randomization.	From randomization to approximately 24 hours
Change in dyspnea 2 days after randomization	Change in dyspnea assessed using a Visual Analogue Scale from randomization to the morning of Day 3, corresponding to approximately 48 hours after randomization.	From randomization to approximately 48 hours
Death from any cause after 30 days	All-cause mortality assessed 30 days after randomization.	From randomization to 30 days
Rehospitalization from any cause after 30 days	Rehospitalization from any cause assessed 30 days after randomization.	From randomization to 30 days
Acute kidney injury	Proportion of participants with acute kidney injury grade 2 or higher as defined by KDIGO criteria during the treatment phase.	From randomization to approximately 72 hours
Severe electrolyte disturbances	Proportion of participants with severe hypokalaemia, severe hyponatremia, or severe hypernatremia, defined as potassium less than 2.5 mmol/L, sodium less than 125 mmol/L, or sodium greater than 155 mmol/L.	From randomization to approximately 72 hours
Incidents and side effects	Treatment-emergent serious adverse events, including incidents and side effects.	From randomization to 30 days

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Central Denmark Region
• Investigators: Study Director: Esben Merrild, MD, Department of Medicine, Randers Regional Hospital; Study Chair: Bo Løfgren, MD PhD, Department of Medicine, Randers Regional Hospital; Study Chair: Henrik Birn, MD PhD DMSc, Department of Renal Medicine, Aarhus University Hospital; Study Chair: Kasper G Lauridsen, MD PhD, Department of Medicine, Randers Regional Hospital; Study Chair: Christian B Poulsen, MD PhD, Private Organization

Publications and helpful links

Helpful Links

• EU Clinical Trials register entry for INFUSE-AHF

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Edema
• Other Study ID Numbers: INFUSEAHF; 2025-523589-26-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data may be made available after publication of the main trial results, subject to approval by the Steering Committee and in accordance with applicable data protection legislation. All trial data will be pseudo-anonymized and stored for 25 years after the end of the trial in accordance with Danish law and GDPR requirements. Data sharing will be considered on a case-by-case basis for scientifically sound research proposals that do not conflict with ongoing or planned analyses, intellectual property considerations, or the governance and objectives of the trial. Requests for data access must be submitted to the Scientific Lead or Coordinating Investigator and will be evaluated by the Steering Committee based on methodological quality, feasibility, and compatibility with the scientific, ethical, and strategic framework of the trial. There is no obligation for unrestricted, automatic, or indefinite data sharing.
• IPD Sharing Time Frame: After publication of the main trial results. Data will be considered available on a case-by-case basis, and there is no predefined end date for availability.
• IPD Sharing Access Criteria: Requests must be submitted to the Scientific Lead or Coordinating Investigator and will be evaluated by the Steering Committee. Access may be granted for scientifically sound research proposals that do not conflict with ongoing or planned analyses, intellectual property considerations, or the governance and objectives of the trial. Requests will be evaluated based on methodological quality, feasibility, and compatibility with the scientific, ethical, and strategic framework of the trial.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No