Edema, Hypoproteinemia
Conditions
Keywords
Edema, Hypoproteinemia, Albumin, Diuresis, Critical illness
Brief summary
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.
Interventions
DRUGIntravenous albumin
DRUGNormal saline
Sponsors
Hamilton Health Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free Days | 30 days | Ventilator-free days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fluid Balance and Body Weight | Day 1, Day 3, Day 5 | Change in total fluid balance and body weight from baseline at 3 days and 5 days |
| Oxygenation | Day 1, Day 3, Day 5 | Changes in oxygenation (FiO2, P/F ratio, oxygenation index) from baseline at day 3 and day 5 |
| Treatment Interruptions | Day 1, Day 2, Day 3 | Number of episodes of interrupting treatment with furosemide (eg. hypotensive episodes, renal failure, contraction alkalosis, etc.) |
| Duration of Mechanical Ventilation | 30 days | Total duration of mechanical ventilation |
| Length of ICU Stay | Study end | — |
| Serum Albumin and Colloid Osmotic Pressure | Day 1, Day 3, Day 5 | Changes in serum albumin and serum colloid osmotic pressure measurements from Day 1, Day 3, Day 5 |
| Mortality | 30 days | Total ICU mortality and mortality at 30 days. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Absence of Co-intervention | Day 3 | Absence of hyperoncotic albumin administration to patients randomized to the control arm |
| Randomization Rate | Study duration | 1. Randomization rate of patients eligible by screening criteria 2. Randomization rate of patients eligible by clinical site |
| Adherence to Protocol | Day 1 | The administration of at least the first dose of study treatment (albumin or placebo) within two hours of the first administration of furosemide |
| Completion of Study Treatment | Day 3 | Patients receiving full 72 hours (6 doses) of study treatment |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Albumin (n=24) Administration of 25% albumin by intravenous infusion, twice daily for a total of 72 hours (6 treatments)
Intravenous albumin | 24 |
| Normal Saline (n=21) Administration of 100 mL normal saline by intravenous infusion, twice daily, for 72 hours (6 treatments)
Normal saline | 21 |
| Total | 45 |
Baseline characteristics
| Characteristic | Intravenous Albumin (n=24) | Normal Saline (n=21) | Total |
|---|---|---|---|
| Age, Continuous | 61.71 years STANDARD_DEVIATION 17.2 | 64.7 years STANDARD_DEVIATION 15.2 | 63.1 years STANDARD_DEVIATION 23 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 13 Participants | 16 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 24 | 4 / 21 |
| serious Total, serious adverse events | 0 / 24 | 0 / 21 |
Outcome results
Primary
Ventilator-free Days
Ventilator-free days
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intravenous Albumin (n=24) | Ventilator-free Days | 4 days |
| Normal Saline (n=21) | Ventilator-free Days | 13 days |
Secondary
Duration of Mechanical Ventilation
Total duration of mechanical ventilation
Time frame: 30 days
Secondary
Fluid Balance and Body Weight
Change in total fluid balance and body weight from baseline at 3 days and 5 days
Time frame: Day 1, Day 3, Day 5
Secondary
Length of ICU Stay
Time frame: Study end
Secondary
Mortality
Total ICU mortality and mortality at 30 days.
Time frame: 30 days
Secondary
Oxygenation
Changes in oxygenation (FiO2, P/F ratio, oxygenation index) from baseline at day 3 and day 5
Time frame: Day 1, Day 3, Day 5
Secondary
Serum Albumin and Colloid Osmotic Pressure
Changes in serum albumin and serum colloid osmotic pressure measurements from Day 1, Day 3, Day 5
Time frame: Day 1, Day 3, Day 5
Secondary
Treatment Interruptions
Number of episodes of interrupting treatment with furosemide (eg. hypotensive episodes, renal failure, contraction alkalosis, etc.)
Time frame: Day 1, Day 2, Day 3
Other Pre-specified
Absence of Co-intervention
Absence of hyperoncotic albumin administration to patients randomized to the control arm
Time frame: Day 3
Other Pre-specified
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
Time frame: Day 1
Other Pre-specified
Completion of Study Treatment
Patients receiving full 72 hours (6 doses) of study treatment
Time frame: Day 3
Other Pre-specified
Randomization Rate
1. Randomization rate of patients eligible by screening criteria 2. Randomization rate of patients eligible by clinical site
Time frame: Study duration