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

• ClinicalTrials.gov Identifier: NCT04180397
• Recruitment Status: Recruiting
• First Posted: November 27, 2019
• Last Update Posted: May 17, 2022
• Sponsor: Morten H. Bestle
• Collaborators: University of Copenhagen; Copenhagen Trial Unit, Center for Clinical Intervention Research; Centre for Research in Intensive Care (CRIC)
• Information provided by (Responsible Party): Morten H. Bestle, Nordsjaellands Hospital

Tracking Information

• First Submitted Date: November 25, 2019
• First Posted Date: November 27, 2019
• Last Update Posted Date: May 17, 2022
• Actual Study Start Date: August 17, 2020
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2020)

Days alive and out of hospital [ Time Frame: 90 days after randomization ]

Days alive and out of hospital

Original Primary Outcome Measures (submitted: November 25, 2019)

Mortality [ Time Frame: 90 days after randomization ]

Days alive and out of hospital

Current Secondary Outcome Measures (submitted: May 11, 2022)

• All cause mortality [ Time Frame: 90 days after randomization ]
  All cause mortality
• Mortality and life support [ Time Frame: 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 [ Time Frame: one year after randomization ]
  All cause mortality
• Serious adverse events and reactions [ Time Frame: 90 days ]
  Number of participants with one or more serious adverse events and serious adverse reactions
• Health related quality of life [ Time Frame: 1 year after randomization ]
  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.
• Cognitive function [ Time Frame: 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 [ Time Frame: 1 year after randomization ]
  Subjective assessment (unacceptable, neutral, acceptable)

Original Secondary Outcome Measures (submitted: November 25, 2019)

• All cause mortality [ Time Frame: 90 days after randomization ]
  All cause mortality
• Mortality and life support [ Time Frame: 90 days after ranodimization ]
  Days alive without life support without life support (vasopressor/inotropic support, invasive mechanical ventilation or renal replacement therapy)
• Mortality 1 year [ Time Frame: one year after randomization ]
  All cause mortilty
• Serious adverse events and reactions [ Time Frame: 90 days ]
  Number of participants with one or more serious adverse events and serious adverse reactions
• Acute kidney injury [ Time Frame: 90 days. ]
  Number of participants developing acute kidney injury and/or recovering from from it during the trial.
• Health related quality of life (HRQoL) [ Time Frame: 1 year after randomization ]
  HRQoL measured using the EuroQoL (EQ)-5D-5L and EQ-VAS scores
• Cognitive function [ Time Frame: 1 year after randomization ]
  Cognitive function assessed by the Montreal Cognitive Assessment score

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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).
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Fluid Overload

Intervention

• Drug: Furosemide
  Furosemide 10 mg/ml for injection/infusion
  Other Name: Furix
• Drug: Isotonic saline
  Isotonic saline used as placebo (injection/infusion)

Study Arms

• 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.
  Intervention: Drug: Furosemide
• 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.
  Intervention: Drug: Isotonic saline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 25, 2019): 1000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 17, 2025
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sine Wichmann, MD; +45 26142620; sine.wichmann@regionh.dk

Contact: Morten Bestle, MD; +45 41951195; morten.bestle@regionh.dk

• Listed Location Countries: Denmark, Finland, Norway

Administrative Information

• NCT Number: NCT04180397
• Other Study ID Numbers: GODIF
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Morten H. Bestle, Nordsjaellands Hospital
• Study 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

• PRS Account: Nordsjaellands Hospital
• Verification Date: May 2022