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Published on: September 24, 2020
Pediatric calfactant in acute respiratory distress syndrome trial
Douglas F Willson1, Neal J Thomas, Robert Tamburro
11Department of Pediatrics, University of Virginia Health Sciences System, Charlottesville, VA. 2Department of Pediatrics, Penn State Hershey M.S. Hershey Medical Center, Hershey, PA. 3Department of Pediatrics, Children's Hospital & Medical Center, University of Nebraska, Omaha, NE. 4Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, VA. 5Public Health Sciences, University of Virginia Health Sciences System, Charlottesville, VA. 6Department of Pediatrics, Children's Hospital Cleveland Clinic, Cleveland, OH. 7Pneuma Pharmaceuticals, Amherst, NY. 8Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY.
Insights
Exogenous surfactant (calfactant) did not improve outcomes in children with direct lung injury/acute respiratory distress syndrome. This trial found no significant difference in mortality or oxygenation compared to placebo, questioning previous findings.
Area of Science:
- Pediatric Critical Care Medicine
- Respiratory Medicine
Background:
- Previous studies suggested improved outcomes with exogenous surfactant (calfactant) in pediatric acute lung injury/acute respiratory distress syndrome (ALI/ARDS).
- However, small sample sizes and heterogeneous populations limited previous recommendations.
Purpose of the Study:
- To evaluate the efficacy of surfactant administration in a larger, more homogenous group of pediatric patients with direct lung injury/acute respiratory distress syndrome.
- To determine if calfactant improves mortality, oxygenation, or ventilator-free days.
Main Methods:
- A masked, randomized, placebo-controlled trial was conducted across 24 international children's hospitals.
- 110 children (37 weeks postconception to 18 years) with direct ALI/ARDS received up to three doses of calfactant or placebo (air) within 48 hours of intubation.
- Primary outcome was 90-day mortality; secondary outcomes included ventilator-free days and oxygenation changes.
Main Results:
- The trial was stopped early for presumed futility. No significant differences in 90-day mortality or immediate oxygenation were observed between surfactant and placebo groups.
- A significant difference was found in hospital-free days, with the placebo group having more (10.4 ± 7.8) than the surfactant group (6.4 ± 7.8; p = 0.01).
- Overall 90-day mortality was 11% (seven surfactant, five placebo).
Conclusions:
- Exogenous surfactant (calfactant) administration did not improve outcomes in children with direct lung injury/acute respiratory distress syndrome in this trial.
- Potential reasons for differing results from previous studies include surfactant concentration, lung recruitment techniques, or patient positioning during administration.
- Current evidence does not support the use of exogenous surfactant for pediatric direct ALI/ARDS.
Rationale:
Our previous studies in children with acute lung injury/acute respiratory distress syndrome demonstrated improved outcomes with exogenous surfactant (calfactant) administration. Sample sizes in those studies were small, however, and the subject populations heterogeneous, thus making recommendations tenuous.
Objective:
To investigate the efficacy of surfactant administration in a larger, more homogenous population of children with lung injury/acute respiratory distress syndrome due to direct lung injury.
Design And Setting:
Masked, randomized, placebo-controlled trial in 24 children's hospitals in six different countries.
Patients And Methods:
Children 37 weeks postconception to 18 years old with lung injury/acute respiratory distress syndrome due to direct lung injury were randomized to receive up to three doses of 30 mg/cm height of surfactant (calfactant) versus placebo (air) within 48 hours of intubation and initiation of mechanical ventilation. The primary outcome was mortality at 90 days. Ventilator-free days, changes in oxygenation, and adverse events were also assessed.
Results:
The study was stopped at the sponsor's request after the second interim analysis for presumed futility. A total of 110 subjects were enrolled, with consent withdrawn from one whose data are unavailable. There were no significant differences between groups except in hospital-free days (10.4 ± 7.8 placebo vs 6.4 ± 7.8 surfactant; p = 0.01). Overall 90-day mortality was 11% (seven surfactant, five placebo). No immediate improvement in oxygenation was associated with surfactant administration.
Conclusions:
Surfactant did not improve outcomes relative to placebo in this trial of children with direct lung injury/acute respiratory distress syndrome. Differences in concentration of the surfactant, failure to recruit the lung during surfactant administration, or using two rather than four position changes during administration are possible explanations for the difference from previous studies. Exogenous surfactant cannot be recommended at this time for children with direct lung injury/acute respiratory distress syndrome.
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