Furosemide and Albumin for Diuresis of Edema: A Pilot Randomized Controlled Trial

Study Overview
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Brief Summary
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Critically ill patients usually require intravenous fluids to correct low blood pressure and improve blood flow to vital organs. However, once the patient's blood pressure has improved, these fluids can leak out into various organs, including the lung, kidneys, and skin. Excess fluid in these tissues, called edema, has been associated with longer ICU stays and higher mortality. Thus removing excess fluid is an important goal. The simplest way to treat edema is to use diuretics, such as furosemide, which increase urine output. To further improve urine output, patients are sometimes given albumin, a protein which helps to suck fluid out from the tissues, and keep it in the blood vessel, where it can be filtered in the kidney and removed in the urine. Although albumin is often used for this purpose, there is little evidence to support it. A large randomized controlled trial is needed to determine if albumin plus furosemide is truly more effective than furosemide alone in critically ill patients with low levels of blood albumin. We will perform a pilot study to assess the feasibility of such a trial.

Official Title
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A Single-centre, Randomized, Double-blinded, Placebo-controlled Pilot Study to Determine the Feasibility of a Full-scale Clinical Trial to Compare the Effect of Furosemide With or Without 25% Albumin in the Diuresis of Edema in Volume-overloaded ICU Patients in the Post-resuscitation Phase of Illness.

Conditions
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Edema, Hypoproteinemia

Intervention / Treatment
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* Drug: Intravenous albumin
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hemodynamically stable for at least 24 hours (absence of persistent [>1 h] hypotension [systolic blood pressure <90 mmHg), not currently on vasopressors, less than 2 L crystalloid or colloid boluses, or 2 units red blood cells administered, maintenance fluids excluded Hypoproteinemia (serum albumin <30 mg/L or total protein < 60 mg/L) Clinical decision to diurese at least 3 L net fluid balance within the next 72 hours for any reason Exclusion Criteria: known pregnancy patient or surrogate unable or unwilling to consent to blood product administration, including albumin history of adverse reactions or allergy to either albumin or furosemide acute kidney injury (RIFLE criteria F or greater) without any improvement in past 24 hours, or otherwise expected to necessitate dialysis within 48 hours in opinion of treating physician chronic kidney injury requiring dialysis clinically documented cirrhosis clinically documented nephrotic syndrome serum sodium greater than 150 milliequivalent/L or serum potassium less than 2.5 mEq/L that connote be treated prior to administration of study treatment inability to measure urine output and fluid balance Receipt of hyperoncotic albumin within preceding 24 hours previous enrollment in this trial, or any research studies which may interfere with this study estimated survival or ICU stay less than 72 hours

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 |
| --- | --- |
| Experimental: Intravenous albumin<br>Administration of 25% albumin by intravenous infusion, twice daily for a total of 72 hours (6 treatments) | Drug: Intravenous albumin<br> <br> |
| Placebo Comparator: Normal saline<br>Administration of 100 mL normal saline by intravenous infusion, twice daily, for 72 hours (6 treatments) | Drug: Normal saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free days | Ventilator-free days | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum albumin and colloid osmotic pressure | Changes in serum albumin and serum colloid osmotic pressure measurements from Day 1, Day 3, Day 5 | Day 1, Day 3, Day 5 | 
| Mortality | Total ICU mortality and mortality at 30 days. | 30 days | 
| Fluid balance and body weight | Change in total fluid balance and body weight from baseline at 3 days and 5 days | Day 1, Day 3, Day 5 | 
| Oxygenation | Changes in oxygenation (FiO2, P/F ratio, oxygenation index) from baseline at day 3 and day 5 | Day 1, Day 3, Day 5 | 
| Treatment interruptions | Number of episodes of interrupting treatment with furosemide (eg. hypotensive episodes, renal failure, contraction alkalosis, etc.) | Day 1, Day 2, Day 3 | 
| Duration of Mechanical Ventilation | Total duration of mechanical ventilation | 30 days | 
| Length of ICU Stay |  | Study end | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diuresis, Edema, Hypoproteinemia, Albumin, Critical illness