Clinical trial NCT04180397: Controlled Fluid Removal in Critical Ill Patients With Fluid Overload in the Intensive Care Unit.
Official title: Goal Directed Fluid Removal With Furosemide in Intensive Care Patients With Fluid Overload - A Randomised, Blinded, Placebo-controlled Trial (GODIF).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Fluid Overload
Keywords: Fluid overload
Fluid removal
Deresusciation
Diuretics
Fluid accumulation
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: Centre for Research in Intensive Care (CRIC)
First posted: 2019-11-27
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Days alive and out of hospital
timeFrame: 90 days after randomization
Secondary outcomes:
measure: All cause mortality
timeFrame: 90 days after randomization
measure: Mortality and life support
timeFrame: 90 days after randomization
measure: Mortality 1 year
timeFrame: one year after randomization
measure: Serious adverse events and reactions
timeFrame: 90 days
measure: Health related quality of life
timeFrame: 1 year after randomization
measure: Cognitive function
timeFrame: 1 year after randomization
measure: Health related quality of life
timeFrame: 1 year after randomization
Other outcomes:
Locations:
city: Sidney
country: Australia
facility: Department of Intensive Care, Liverpool Hospital
city: Aabenraa
country: Denmark
facility: Department of Intensive Care, Sygehus Sønderjylland Aabenraa
city: Aalborg
country: Denmark
facility: Departmen of Intensive Care
city: Aarhus
country: Denmark
facility: Department of Intensive Care, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Intensive Care, Rigshospitalet
city: Gentofte
country: Denmark
facility: Departement of Intensive Care, Gentofte Hospital
city: Herlev
country: Denmark
facility: Department of Intensive Care, Herlev Hospital
city: Herning
country: Denmark
facility: Department of Intensive Care, Regionshospital Gødstrup
city: Hillerød
country: Denmark
facility: Department of Intensive Care, Nordsjællands hospital
city: Hjørring
country: Denmark
facility: Department of Intensive Care, Regionshospital Nordjylland Hjørring
city: Kolding
country: Denmark
facility: Department of Intensive Care
city: Køge
country: Denmark
facility: Department of Intensive Care, Zealand University hospital
city: Odense
country: Denmark
facility: Department of Intensive Care
city: Randers
country: Denmark
facility: Department of Intensive Care, Regionshospitalet Randers
city: Roskilde
country: Denmark
facility: Department of Intensive Care, University Hospital Zealand, Roskilde
city: Vejle
country: Denmark
facility: Department of Intensive Care
city: Viborg
country: Denmark
facility: Regionshospitalet Viborg
city: Tampere
country: Finland
facility: Department of Intensive Care, Tampere University Hospital
city: Turku
country: Finland
facility: Department of Intensive Care
city: Reykjavík
country: Iceland
facility: Department of Intensive Care, Landspitali National University Hospital of Iceland
city: Groningen
country: Netherlands
facility: Department of Critical Care, University Medical Center Groningen
city: Stavanger
country: Norway
facility: Department of Intensive Care, Stavanger University Hospital
city: Ålesund
country: Norway
facility: Department of Intensive Care, Ålesund Sjukehus
city: Bern
country: Switzerland
facility: Department of Intensive Care, Inselspital
Study officials:
affiliation: Department of Anaesthesiology and Intensive Care medicine Nordsjællands hospital
name: Morten Bestle, MD
role: STUDY_CHAIR
References:
citation: Wichmann S, Itenov TS, Berthelsen RE, Lange T, Perner A, Gluud C, Lawson-Smith P, Nebrich L, Wiis J, Brochner AC, Hildebrandt T, Behzadi MT, Strand K, Andersen FH, Strom T, Jarvisalo M, Damgaard KAJ, Vang ML, Wahlin RR, Sigurdsson MI, Thormar KM, Ostermann M, Keus F, Bestle MH. Goal directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A trial protocol for a randomised, blinded trial (GODIF trial). Acta Anaesthesiol Scand. 2022 Oct;66(9):1138-1145. doi: 10.1111/aas.14121. Epub 2022 Aug 9.