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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Goal Directed Fluid Removal With Furosemide in Intensive Care Patients With Fluid Overload - A Randomised, Blinded, Placebo-controlled Trial (GODIF).

Conditions
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Fluid Overload

Intervention / Treatment
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* Drug: Furosemide
* Drug: Isotonic saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Furosemide<br>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<br>* Furosemide 10 mg/ml for injection/infusion<br>* Other names: Furix;|
| Placebo Comparator: Placebo<br>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<br>* Isotonic saline used as placebo (injection/infusion)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid overload, Fluid removal, Deresusciation, Diuretics, Fluid accumulation