Abstract
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 A total of 110 subjects were enrolled, with consent withdrawn from one whose data are unavailable.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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 657-665 |
| Number of pages | 9 |
| Journal | Pediatric Critical Care Medicine |
| Volume | 14 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jan 1 2013 |
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Keywords
- Acute lung injury
- Acute respiratory distress syndrome
- Calfactant
- Direct lung injury
- Hypoxemia index
- Oxygen saturation index
- Recruitment maneuver
- Respiratory failure
- Surfactant
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Critical Care and Intensive Care Medicine
Cite this
Pediatric calfactant in acute respiratory distress syndrome trial. / Willson, Douglas F.; Thomas, Neal J.; Tamburro, Robert; Truemper, Edward J; Truwit, Jonathon; Conaway, Mark; Traul, Christine; Egan, Edmund E.
In: Pediatric Critical Care Medicine, Vol. 14, No. 7, 01.01.2013, p. 657-665.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pediatric calfactant in acute respiratory distress syndrome trial
AU - Willson, Douglas F.
AU - Thomas, Neal J.
AU - Tamburro, Robert
AU - Truemper, Edward J
AU - Truwit, Jonathon
AU - Conaway, Mark
AU - Traul, Christine
AU - Egan, Edmund E.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Acute lung injury
KW - Acute respiratory distress syndrome
KW - Calfactant
KW - Direct lung injury
KW - Hypoxemia index
KW - Oxygen saturation index
KW - Recruitment maneuver
KW - Respiratory failure
KW - Surfactant
UR - http://www.scopus.com/inward/record.url?scp=84898733562&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898733562&partnerID=8YFLogxK
U2 - 10.1097/PCC.0b013e3182917b68
DO - 10.1097/PCC.0b013e3182917b68
M3 - Article
VL - 14
SP - 657
EP - 665
JO - Pediatric Critical Care Medicine
JF - Pediatric Critical Care Medicine
SN - 1529-7535
IS - 7
ER -