Controlled Fluid Removal in Critical Ill Patients With Fluid Overload in the Intensive Care Unit.

Phase 4

Recruiting

• Conditions: Fluid Overload
• Interventions: Drug: Isotonic saline; Drug: Furosemide

• Registration Number: NCT04180397
• Lead Sponsor: Morten H. Bestle

Brief Summary

This study evaluates the benefits and harms of goal directed fluid removal with furosemide versus placebo in critical ill adult patients with fluid overload in the intensive care unit. Half of the patients will receive furosemide and the other half placebo. The treatment will continue until the excess fluid is excreted.

Detailed Description

Fluid overload is a common and serious complication in patients admitted to the intensive care unit (ICU). A core element of therapy in the ICU is resuscitation with crystalloid solutions. In many cases fluid accumulate, and patients become fluid overloaded. Several observational studies indicate a detrimental effect of fluid overload in different clinical settings, including patients with acute kidney injury. It is unknown whether this association is causal or if the increased tendency to accumulate fluid is a marker of disease severity and thereby a higher risk of death. The investigators want to investigate this in critical ill patients with fluid overload of 5% or more by randomizing them to furosemide (diuretics) or placebo.

Study Timeline

• Study First Submitted: 2019-11-25
• Study First Submitted QC: 2019-11-25
• Study First Posted: 2019-11-27
• Study Start: 2020-08-17
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-05
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-12-31
• Study Completion: 2028-03-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

ALL below must be met.

• Acute admission to the intensive care unit.
• Age ≥ 18 years of age
• Fluid overload ≥ 5% of ideal body weight. If possible, all fluids administered before admission to the intensive care unit are to be included in the calculation of cumulative fluid balance.
• Clinical stable (minimum criteria: MAP > 50 mmHg and maximum infusion of 20 microgram/kg/minute of noradrenaline and lactate < 4.0 mmol/L)

Exclusion Criteria

• Known allergy to furosemide or sulphonamides.
• Known pre-hospitalization advanced chronic kidney disease (eGFR < 30 mL/minute/1.73 m^2 or chronic RRT).
• Ongoing renal replacement therapy.
• Anuria > 6 hours.
• Rhabdomyolysis with indication for forced diuresis
• Ongoing life-threatening bleeding as these patients need specific fluid/blood product strategies.
• Acute burn injury of more than 10% of the body surface area as these patients need a specific fluid strategy.
• Severe dysnatremia (p-Na < 120 or > 155 mmol/L) as these patients need a specific fluid strategy.
• Severe hepatic failure as per the clinical team.
• Patients undergoing forced treatment.
• Fertile women (women < 50 years) with positive urine human chorionic gonadotropin (hCG) or plasma-hCG.
• Consent not obtainable as per the model approved for the specific trial site.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Isotonic saline	Isotonic saline dosed the same way and by the same algorithm as for furosemide. Start bolus of 0.5-4 ml at physicians discretion. Infusion rate: 0 - 4 ml/hour. Infusion is started at 2 ml/hour and adjusted according to effect. Target is a negative fluid balance of 1 ml/kg/hour. The fluid balance is calculated 3 times a dag at 6:00 am, 2:00 pm and 10:00 pm. Goal directed fluid removal is stopped when the fluid balance is assessed neutral.
Furosemide	Furosemide	Bolus of 5-40 mg (0.5 - 4 ml) of furosemide iv at physicians discretion followed by infusion of furosemide. Infusion rate: 0-40 mg/hour. Starting rate: 20 mg/hour. The infusion is adjusted according effect. Target is a negative fluid balance of 1 ml/kg/hour. The fluid balance is calculated 3 times a dag at 6:00 am, 2:00 pm and 10:00 pm. Goal directed fluid removal is stopped when the fluid balance is assessed neutral.

Primary Outcome Measures

Name	Time	Method
Days alive and out of hospital	90 days after randomization	Days alive and out of hospital

Secondary Outcome Measures

Name	Time	Method
All cause mortality	90 days after randomization	All cause mortality
Cognitive function	1 year after randomization	Cognitive function assessed by the Montreal Cognitive Assessment score. Using the mini test for telephone interview. The test and scoring system will soon be published from Montreal Cognitive Assessment.
Health related quality of life	1 year after randomization	Subjective assessment (unacceptable, neutral, acceptable)
Serious adverse events and reactions	90 days	Number of participants with one or more serious adverse events and serious adverse reactions
Mortality and life support	90 days after randomization	Days alive without life support without life support (vasopressor/inotropic support, invasive mechanical ventilation or renal replacement therapy)
Mortality 1 year	one year after randomization	All cause mortality

Trial Locations

Locations (21)

Department of Intensive Care, Liverpool Hospital; 🇦🇺 Sidney, Australia

Department of Intensive Care, Sygehus Sønderjylland Aabenraa; 🇩🇰 Aabenraa, Denmark

Departmen of Intensive Care; 🇩🇰 Aalborg, Denmark

Department of Intensive Care, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Department of Intensive Care, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Departement of Intensive Care, Gentofte Hospital; 🇩🇰 Gentofte, Denmark

Department of Intensive Care, Herlev Hospital; 🇩🇰 Herlev, Denmark

Department of Intensive Care, Regionshospital Gødstrup; 🇩🇰 Herning, Denmark

Department of Intensive Care, Nordsjællands hospital; 🇩🇰 Hillerød, Denmark

Department of Intensive Care, Regionshospital Nordjylland Hjørring; 🇩🇰 Hjørring, Denmark

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