Skip to main content

Table 2 Variables, measures, and methods of analysis

From: Furosemide and albumin for diuresis of edema (FADE): a study protocol for a randomized controlled trial

Outcome Hypothesis Outcome measure Covariates Methods of analysis
Feasibility outcomes
Adherence to treatment >85% adherence Proportion receiving first dose of study treatment within 2 hours of furosemide None 95% confidence interval of a proportion
Completion of treatment >80% completion Proportion receiving all six doses of study treatment None 95% confidence interval of a proportion
Absence of hyperoncotic albumin in control arm >85% in control group without 25% albumin Proportion of patients assigned to control receiving no 25% albumin None 95% confidence interval of a proportion
Randomization rate of eligible patients >50% of eligible patients recruited Proportion of eligible patients randomized None 95% confidence interval of a proportion
Randomization rate of patients by clinical site Average recruitment of one patient per site per week Rate of recruitment per week None Average rate of recruitment
Clinical outcomes
Primary outcome
Duration of mechanical ventilation Increased number of ventilator-free days in treatment group Number of ventilator-free days Duration of ventilation at time of randomization t test, linear regression
Secondary outcomes
Duration of mechanical ventilation Decreased duration of mechanical ventilation in treatment group Duration of mechanical ventilation (days) Duration of ventilation at time of randomization t test, linear regression
Episodes interrupting treatment with furosemide Fewer episodes of interruption in treatment group Number of episodes None t test
Need for dialysis Smaller proportion of patients requiring dialysis in treatment group during ICU stay Proportion of patients requiring dialysis during 30 days None Chi-squared or Fisher’s exact statistic
Length of ICU stay Shorter length of stay in treatment group Duration of ICU stay Duration of ICU stay at time of randomization t test, linear regression
ICU mortality Decreased ICU mortality in treatment group during ICU stay All-cause mortality (binary) APACHE-2 and SOFA scores at randomization Kaplan-Meyer survival curve (time to death)
30-day mortality Decreased 30-day mortality in treatment group All-cause mortality (binary) APACHE-2 and SOFA scores at randomization Kaplan-Meyer survival curve (time to death)
Physiologic outcomes
Change in oxygenation Greater increase PaO2/FiO2 ratio in treatment group at day 3 and day 5 Change in PaO2/FiO2 ratio None t test
  Greater decrease in oxygenation index in treatment group at day 3 and day 5 Change in oxygenation index None t test
Change in lung compliance Greater increase in dynamic compliance in treatment group at day 3 and day 5 Change in dynamic compliance during study treatment (ml/cmH2O) None t test
Change in fluid balance Greater net decrease in fluid balance in treatment group at day 3 and day 5 Change in net fluid balance (ml) Net fluid balance at time of randomization t test, linear regression
Change in body weight Greater decrease in body weight in treatment group at day 3 and day 5 Change in body weight (kg) Baseline weight t test, linear regression
Urine output Greater net urine output in treatment group at day 3 and day 5 Urine output during 3 days of study treatment (ml) Net fluid balance at time of randomization t test, linear regression
Dose of furosemide Lower total amount of furosemide used in treatment group at day 3 Dose of furosemide during 3 days of study treatment (mg) None t test
Changes in serum albumin Greater increase in serum albumin level in treatment group at day 3 and day 5 Change in serum albumin (g/l) None t test
Changes in colloid osmotic pressure Greater increase in colloid osmotic pressure in treatment group at day 3 and day 5 Change in colloid osmotic pressure (mmHg) None t test
Changes in serum total protein Greater increase in total protein in treatment group at day 3 and day 5 Change in total protein (g/l) None t test
Change in electrolytes No difference between study groups for major electrolytes (sodium, potassium) at day 3 and day 5 Change in electrolytes between beginning and end of study treatment (mEq/l) None t test
Subgroup analyses
ARDS Improved oxygenation in patients with ARDS   None Regression methods with appropriate interaction term
Severity of disease Improved hemodynamic stability in patients with severe disease   None Regression methods with appropriate interaction term
Time since recovery of hemodynamic stability Improved hemodynamic stability in patients with recent hemodynamic instability >48 hours versus <48 hours of hemodynamic stability (as defined by study eligibility criteria) None Regression methods with appropriate interaction term
Sensitivity analyses
Per-protocol analysis   All outcomes None  
Adjusting for baseline covariates   All outcomes As described Multivariable regression
Adjusted for dose of furosemide Treatment with albumin results in improvement beyond that explained by dose of furosemide All outcomes Dose of furosemide Multivariable regression
  1. APACHE-2, Acute Physiology and Chronic Health Evaluation-2; ARDS, acute respiratory distress syndrome; FiO2,, fraction of inspired oxygen; ICU, intensive care unit; PaO2, partial pressure of oxygen in arterial blood; SOFA, Sepsis-related Organ Failure Assessment.