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

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.

Study Overview

• Status: Recruiting
• Conditions: Fluid Overload
• Intervention / Treatment: Drug: Furosemide; Drug: Isotonic saline

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 Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sine Wichmann, MD; Phone Number: +45 26142620; Email: sine.wichmann@regionh.dk
• Study Contact Backup: Name: Morten Bestle, MD; Phone Number: +45 41951195; Email: morten.bestle@regionh.dk

Study Locations

• Denmark
  • Aabenraa, Denmark
    • Recruiting
    • Department of Intensive Care, Sygehus Sønderjylland Aabenraa
    • Principal Investigator: Thomas Strøm, Professor
  • Aalborg, Denmark, 9000
    • Recruiting
    • Departmen of Intensive Care
    • Principal Investigator: Meike T Behazadi, MD
  • Aarhus, Denmark
    • Recruiting
    • Dorte Illum
    • Principal Investigator: Dorte Illum, MD
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Department of Intensive Care, Rigshospitalet
    • Principal Investigator: Anders Bastiansen, MD
  • Gentofte, Denmark
    • Recruiting
    • Departement of Intensive Care, Gentofte Hospital
    • Principal Investigator: Camilla Eschen, MD
  • Herlev, Denmark, 2730
    • Recruiting
    • Department of Intensive Care, Herlev Hospital
    • Principal Investigator: Anne Sofie Andreasen, MD, PhD
  • Herning, Denmark, 7400
    • Recruiting
    • Department of Intensive Care, Regionshospital Gødstrup
    • Contact: Thomas Troelsen, MD
    • Principal Investigator: Sandra Thygesen, MD, PhD
  • Hillerød, Denmark, 3400
    • Recruiting
    • Department of Intensive Care, Nordsjællands hospital
    • Principal Investigator: Sine Wichmann, MD
  • Hjørring, Denmark
    • Recruiting
    • Department of Intensive Care, Regionshospital Nordjylland Hjørring
    • Contact: Kjeld Damgaard
    • Principal Investigator: Kjeld Damgaard
  • Kolding, Denmark, 6000
    • Recruiting
    • Department of Intensive Care
    • Principal Investigator: Anne C Brøchner, MD, PhD
  • Køge, Denmark, 4600
    • Recruiting
    • Department of Intensive Care, Zealand University hospital
    • Principal Investigator: Lars Nebrich, MD
  • Odense, Denmark, 5000
    • Recruiting
    • Department of Intensive Care
    • Principal Investigator: Louise G Nielsen, MD
  • Randers, Denmark, 8930
    • Recruiting
    • Department of Intensive Care, Regionshospitalet Randers
    • Principal Investigator: Marianne Vang, MD
  • Roskilde, Denmark
    • Recruiting
    • Department of Intensive Care, University Hospital Zealand, Roskilde
    • Principal Investigator: Thomas Hildebrandt, MD
  • Vejle, Denmark, 7100
    • Active, not recruiting
    • Department of Intensive Care
  • Viborg, Denmark, 8800
    • Recruiting
    • Regionshospitalet Viborg
    • Principal Investigator: Christoffer Grant Sølling, MD, PhD
• Finland
  • Tampere, Finland, 33520
    • Recruiting
    • Department of Intensive Care, Tampere University Hospital
    • Principal Investigator: Ville Jalkanen, MD
  • Turku, Finland
    • Recruiting
    • Department of Intensive Care
    • Principal Investigator: Panu Uusalo, MD
• Iceland
  • Reykjavík, Iceland
    • Recruiting
    • Department of Intensive Care, Landspitali National University Hospital of Iceland
    • Contact: Martin I Sigurdsson, professor
    • Principal Investigator: Katrin Thormar, MD
• Netherlands
  • Groningen, Netherlands
    • Recruiting
    • Department of Critical Care, University Medical Center Groningen
    • Principal Investigator: Eric Keus, MD
• Norway
  • Stavanger, Norway, 4068
    • Recruiting
    • Department of Intensive Care, Stavanger University Hospital
    • Principal Investigator: Kristian Strand, MD, PhD
  • Ålesund, Norway
    • Recruiting
    • Department of Intensive Care, Ålesund Sjukehus
    • Principal Investigator: Finn H Andersen, MD, PhD
• Switzerland
  • Bern, Switzerland
    • Recruiting
    • Department of Intensive Care, Inselspital
    • Contact: Carmen Pfortmueller, MD, PhD
    • Principal Investigator: Jan Waskowski, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Furosemide; Furosemide 10 mg/ml for injection/infusion; Other Names: Furix
Placebo Comparator: Placebo; 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; Isotonic saline used as placebo (injection/infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive and out of hospital	Days alive and out of hospital	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	All cause mortality	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)	90 days after randomization
Mortality 1 year	All cause mortality	one year after randomization
Serious adverse events and reactions	Number of participants with one or more serious adverse events and serious adverse reactions	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.	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.	1 year after randomization
Health related quality of life	Subjective assessment (unacceptable, neutral, acceptable)	1 year after randomization

Collaborators and Investigators

• Sponsor: Morten H. Bestle
• Collaborators: University of Copenhagen; Copenhagen Trial Unit, Center for Clinical Intervention Research; Centre for Research in Intensive Care (CRIC)
• Investigators: Study Chair: Morten Bestle, MD, Department of Anaesthesiology and Intensive Care medicine Nordsjællands hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 17, 2025

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Diuretics; Fluid overload; Fluid removal; Deresusciation; Fluid accumulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: GODIF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: will be made available on reasonable request after the primary results are published
• 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