Fluid OverloadPhase 4GODIFNCT04180397
Controlled Fluid Removal in Critical Ill Patients With Fluid Overload in the Intensive Care Unit.
A Phase 4 study testing Furosemide and Isotonic saline in people with Fluid Overload, run by Morten H. Bestle at 29 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fluid Overload
- What is being tested?
- Furosemide and Isotonic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- 29 sitesin 9 countries
- Study dates
- 17 Aug 2020to 15 Apr 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
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- 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.
Trial locations and contacts
29 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
29 sites in 9 countries
Denmark16 sites, 12 recruiting
- Terminated
Department of Intensive Care, Sygehus Sønderjylland Aabenraa
Aabenraa
- Recruiting
Departmen of Intensive Care
Aalborg, 9000
Meike T Behazadi, MD
- Terminated
Department of Intensive Care, Aarhus University Hospital
Aarhus
- Recruiting
Department of Intensive Care, Rigshospitalet
Copenhagen, 2100
Anders Bastiansen, MD
- Terminated
Departement of Intensive Care, Gentofte Hospital
Gentofte Municipality
- Recruiting
Department of Intensive Care, Herlev Hospital
Herlev, 2730
Anne Sofie Andreasen, MD, PhD
- Recruiting
Department of Intensive Care, Regionshospital Gødstrup
Herning, 7400
Thomas Troelsen, MD
- Recruiting
Department of Intensive Care, Nordsjællands hospital
Hillerød
Sine Wichmann, MD, PhD, Ass. professor
- Recruiting
Department of Intensive Care, Regionshospital Nordjylland Hjørring
Hjørring
Kjeld Damgaard, MD, PhD
- Recruiting
Department of Intensive Care, Zealand University hospital
Køge, 4600
Lars Nebrich, MD
- Recruiting
Department of Intensive Care
Kolding, 6000
Anne C Brøchner, MD, PhD
- Recruiting
Department of Intensive Care
Odense, 5000
Louise G Nielsen, MD
- Recruiting
Department of Intensive Care, Regionshospitalet Randers
Randers, 8930
Marianne Vang, MD
- Recruiting
Department of Intensive Care, University Hospital Zealand, Roskilde
Roskilde
Thomas Hildebrandt, MD
- Withdrawn
Department of Intensive Care
Vejle, 7100
- Recruiting
Regionshospitalet Viborg
Viborg, 8800
Christoffer Grant Sølling, MD, PhD
Czechia3 sites, 3 recruiting
- Not yet recruiting
Department of Intensive Care, University Hospital of Ostrava
Ostrava
Jan Máca, MD, PhD
- Recruiting
Department of Intensive Care, University Hospital of Pilsen
Pilsen
Marek Nalos, MD, PhD
- Recruiting
Department of Intensive Care, IKEM
Prague
Petr Piza, MD
Australia2 sites, 2 recruiting
- Recruiting
Department of Intensive Care, Liverpool Hospital
Sydney
Anders Aneman, MD, PhD
- Recruiting
Department of Intensive Care, Royal North Shore Hospital
Sydney
Anthony Delaney, Ass. professor
Finland2 sites
- Terminated
Department of Intensive Care, Tampere University Hospital
Tampere, 33520
- Terminated
Department of Intensive Care
Turku
Norway2 sites
- Terminated
Department of Intensive Care, Ålesund Sjukehus
Ålesund
- Terminated
Department of Intensive Care, Stavanger University Hospital
Stavanger, 4068
Iceland1 site
- Terminated
Department of Intensive Care, Landspitali National University Hospital of Iceland
Reykjavik
Lithuania1 site, 1 recruiting
- Recruiting
Vilnius University Hospital Santaros Clinics
Vilnius
Ieva Jovaišienė, Professor
Netherlands1 site, 1 recruiting
- Recruiting
Department of Critical Care, University Medical Center Groningen
Groningen
Eric Keus, MD
Switzerland1 site, 1 recruiting
- Recruiting
Department of Intensive Care, Inselspital
Bern
Carmen Pfortmueller, MD, PhD
Jan Waskowski, MD, PhD
About this study
Official title: Goal Directed Fluid Removal With Furosemide in Intensive Care Patients With Fluid Overload - A Randomised, Blinded, Placebo-controlled Trial (GODIF).
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.
Read the 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.
- Conditions
- Fluid Overload
- Being tested
- Furosemide, Isotonic saline
- Keywords
- Fluid overload, Fluid removal, Deresusciation, Diuretics, Fluid accumulation
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FurosemideDrug
Also called Furix
Furosemide 10 mg/ml for injection/infusion
Isotonic salineDrug
Isotonic saline used as placebo (injection/infusion)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Isotonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive and out of hospital
Days alive and out of hospital
Measured: 90 days after randomization
Secondary outcomes (7)
All cause mortality
All cause mortality
Measured: 90 days after randomization
Mortality and life support
Days alive without life support without life support (vasopressor/inotropic support, invasive mechanical ventilation or renal replacement therapy)
Measured: 90 days after randomization
Mortality 1 year
All cause mortality
Measured: one year after randomization
Serious adverse events and reactions
Number of participants with one or more serious adverse events and serious adverse reactions
Measured: 90 days
Health related quality of life
Measured using the European quality of Life 5D-5L questionnaire (5D-5L is the full name of the questionnaire). Index value of 1 represents full health and dead = 0. These value sets reflect the preferences of the general population. The European quality of life visual analogue scale is a self-reported assessment of the participant's health status. Scores on 100 = the best health you can imagine and 0 = the worst health you can imagine.
Measured: 1 year after randomization
Cognitive function
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.
Measured: 1 year after randomization
Health related quality of life
Subjective assessment (unacceptable, neutral, acceptable)
Measured: 1 year after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2019
- Study start17 Aug 2020
- Primary completion30 Apr 2027 (estimated)
- Study completion15 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fluid OverloadStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Morten H. Bestle
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen, Copenhagen Trial Unit, Center for Clinical Intervention Research, Centre for Research in Intensive Care (CRIC)
- Responsible party
- Sponsor-investigator, Morten H. Bestle, Nordsjaellands Hospital
- Investigators
- Morten Bestle, MD, Study chair, Department of Anaesthesiology and Intensive Care medicine Nordsjællands hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04180397
- Sponsor's protocol ID
- GODIF
- Other IDs
- 2024-512186-14-00, 2019-004292-40, 2019
- Acronym
- GODIF
- Status last verified
- Jun 2026
- First submitted
- 25 Nov 2019
- Last updated
- 3 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: will be made available on reasonable request after the primary results are published
Publications
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.
PubMed 37691474Wichmann 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.
PubMed 35898170