NCT04180397

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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,000

participants targeted

Target at P75+ for phase_4

Timeline
22mo left

Started Aug 2020

Longer than P75 for phase_4

Geographic Reach
9 countries

29 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress76%
Aug 2020Apr 2028

First Submitted

Initial submission to the registry

November 25, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 27, 2019

Completed
9 months until next milestone

Study Start

First participant enrolled

August 17, 2020

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2027

Expected
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 15, 2028

Last Updated

June 3, 2026

Status Verified

June 1, 2026

Enrollment Period

6.7 years

First QC Date

November 25, 2019

Last Update Submit

June 2, 2026

Conditions

Fluid Overload

Keywords

Fluid overloadFluid removalDeresusciationDiureticsFluid accumulation

Outcome Measures

Primary Outcomes (1)

  • Days alive and out of hospital

    Days alive and out of hospital

    90 days after randomization

Secondary Outcomes (7)

  • All cause mortality

    90 days after randomization

  • Mortality and life support

    90 days after randomization

  • Mortality 1 year

    one year after randomization

  • Serious adverse events and reactions

    90 days

  • Health related quality of life

    1 year after randomization

  • +2 more secondary outcomes

Study Arms (2)

Furosemide

ACTIVE COMPARATOR

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.

Drug: Furosemide

Placebo

PLACEBO COMPARATOR

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.

Drug: Isotonic saline

Interventions

FurosemideDRUG

Furosemide 10 mg/ml for injection/infusion

Also known as: Furix
Furosemide
Isotonic salineDRUG

Isotonic saline used as placebo (injection/infusion)

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Department of Intensive Care, Liverpool Hospital

Sydney, Australia

RECRUITING

Department of Intensive Care, Royal North Shore Hospital

Sydney, Australia

RECRUITING

Department of Intensive Care, University Hospital of Ostrava

Ostrava, Czechia

NOT YET RECRUITING

Department of Intensive Care, University Hospital of Pilsen

Pilsen, Czechia

RECRUITING

Department of Intensive Care, IKEM

Prague, Czechia

RECRUITING

Department of Intensive Care, Sygehus Sønderjylland Aabenraa

Aabenraa, Denmark

TERMINATED

Departmen of Intensive Care

Aalborg, 9000, Denmark

RECRUITING

Department of Intensive Care, Aarhus University Hospital

Aarhus, Denmark

TERMINATED

Department of Intensive Care, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Departement of Intensive Care, Gentofte Hospital

Gentofte Municipality, Denmark

TERMINATED

Department of Intensive Care, Herlev Hospital

Herlev, 2730, Denmark

RECRUITING

Department of Intensive Care, Regionshospital Gødstrup

Herning, 7400, Denmark

RECRUITING

Department of Intensive Care, Nordsjællands hospital

Hillerød, Denmark

RECRUITING

Department of Intensive Care, Regionshospital Nordjylland Hjørring

Hjørring, Denmark

RECRUITING

Department of Intensive Care

Kolding, 6000, Denmark

RECRUITING

Department of Intensive Care, Zealand University hospital

Køge, 4600, Denmark

RECRUITING

Department of Intensive Care

Odense, 5000, Denmark

RECRUITING

Department of Intensive Care, Regionshospitalet Randers

Randers, 8930, Denmark

RECRUITING

Department of Intensive Care, University Hospital Zealand, Roskilde

Roskilde, Denmark

RECRUITING

Department of Intensive Care

Vejle, 7100, Denmark

WITHDRAWN

Regionshospitalet Viborg

Viborg, 8800, Denmark

RECRUITING

Department of Intensive Care, Tampere University Hospital

Tampere, 33520, Finland

TERMINATED

Department of Intensive Care

Turku, Finland

TERMINATED

Department of Intensive Care, Landspitali National University Hospital of Iceland

Reykjavik, Iceland

TERMINATED

Vilnius University Hospital Santaros Clinics

Vilnius, Lithuania

RECRUITING

Department of Critical Care, University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Department of Intensive Care, Ålesund Sjukehus

Ålesund, Norway

TERMINATED

Department of Intensive Care, Stavanger University Hospital

Stavanger, 4068, Norway

TERMINATED

Department of Intensive Care, Inselspital

Bern, Switzerland

RECRUITING

Related Publications (2)

  • Wichmann S, Lange T, Perner A, Gluud C, Itenov TS, Berthelsen RE, Nebrich L, Wiis J, Brochner AC, Nielsen LG, Behzadi MT, Damgaard K, Andreasen AS, Strand K, Jarvisalo M, Strom T, Eschen CT, Vang ML, Hildebrandt T, Andersen FH, Sigurdsson MI, Thomar KM, Thygesen SK, Troelsen TT, Uusalo P, Jalkanen V, Illum D, Solling C, Keus F, Pfortmueller CA, Wahlin RR, Ostermann M, Aneman A, Bestle MH. Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan. Acta Anaesthesiol Scand. 2024 Jan;68(1):130-136. doi: 10.1111/aas.14320. Epub 2023 Sep 11.

    PMID: 37691474DERIVED

  • 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.

    PMID: 35898170DERIVED

MeSH Terms

Conditions

Edema

Interventions

FurosemideSodium Chloride

Condition Hierarchy (Ancestors)

Signs and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

SulfanilamidesSulfonamidesAmidesOrganic ChemicalsAniline CompoundsAminesSulfonesSulfur CompoundsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Morten Bestle, MD

    Department of Anaesthesiology and Intensive Care medicine Nordsjællands hospital

    STUDY CHAIR

Central Study Contacts

Sine Wichmann, MD

CONTACT

+45 26142620sine.wichmann@regionh.dk

Morten Bestle, MD

CONTACT

+45 41951195morten.bestle@regionh.dk

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Senior staff specialist and Professor

Study Record Dates

First Submitted

November 25, 2019

First Posted

November 27, 2019

Study Start

August 17, 2020

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

April 15, 2028

Last Updated

June 3, 2026

Record last verified: 2026-06

Data Sharing

IPD Sharing
Will share

will be made available on reasonable request after the primary results are published

Shared Documents
STUDY PROTOCOL, SAP, ICF

Locations

DK(16)AU(2)NO(2)FI(2)IC(1)NL(1)CH(1)CZ(3)LI(1)