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

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.

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.

Study Overview

• Status: Completed
• Conditions: Edema; Hypoproteinemia
• Intervention / Treatment: Drug: Normal saline; Drug: Intravenous albumin

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences

Participation Criteria

Eligibility Criteria

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

Description

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

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

What is the study measuring?

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
Mortality	Total ICU mortality and mortality at 30 days.	30 days
Oxygenation	Changes in oxygenation (FiO2, P/F ratio, oxygenation index) from baseline at day 3 and day 5	Day 1, Day 3, Day 5
Duration of Mechanical Ventilation	Total duration of mechanical ventilation	30 days
Length of ICU Stay		Study end
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
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
Treatment Interruptions	Number of episodes of interrupting treatment with furosemide (eg. hypotensive episodes, renal failure, contraction alkalosis, etc.)	Day 1, Day 2, Day 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to Protocol	The administration of at least the first dose of study treatment (albumin or placebo) within two hours of the first administration of furosemide	Day 1
Completion of Study Treatment	Patients receiving full 72 hours (6 doses) of study treatment	Day 3
Absence of Co-intervention	Absence of hyperoncotic albumin administration to patients randomized to the control arm	Day 3
Randomization Rate	Randomization rate of patients eligible by screening criteria; Randomization rate of patients eligible by clinical site	Study duration

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Simon Oczkowski, MD, McMaster University

Publications and helpful links

General Publications

• Oczkowski SJ, Mazzetti I, Meade MO, Hamielec C. Furosemide and albumin for diuresis of edema (FADE): a study protocol for a randomized controlled trial. Trials. 2014 Jun 12;15:222. doi: 10.1186/1745-6215-15-222.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimated): February 5, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Edema; Critical illness; Diuresis; Albumin; Hypoproteinemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Protein Disorders; Edema; Hypoproteinemia
• Other Study ID Numbers: NIF-13343