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 A total of 110 subjects were enrolled, with consent withdrawn from one whose data are unavailable.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.
1Department 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.
* See also p. 716.
Supported, in part, by Pneuma Pharmaceuticals, Amherst, NY.
The University of Virginia received compensation from Pneuma Pharmaceuticals to support, in part, the salaries of Drs. Willson, Truwit, Conaway, and Traul. Collaborating investigators were paid compensation for subjects successfully enrolled in the study and support for the work of their research assistants.
Dr. Willson received grant support from Pneuma Pharmaceuticals, support as a study coordinator, partial salary support, and capitation for enrolled subjects. Dr. Thomas received grant support from Pneuma Pharmaceuticals and served as a consultant for Discovery Laboratories. Dr. Tamburro received funding on a per patient basis (participating site in the trial) and received grant support from ONY, Inc. Dr. Truemper received grant support and support for travel from the University of Nebraska College of Medicine, provisions of the study drug (Cattactant - supplied to Children's Hospital and Medical Center for the duration of the trial), and lectured for the Nebraska Society of Respiratory Care. Dr. Truwit received support for travel from Pneuma Pharmaceuticals and grant support from Pneuma Pharmaceuticals, NIH, and ARDSNet. Dr. Conaway received support for participation in review activities from Pneuma Pharmaceuticals. Dr. Traul received grant support and support for travel from Pneuma Pharmaceuticals. Dr. Egan served as the unsalaried chairman and chief medical officer for Pneuma Pharmaceuticals, provided expert testimony for various insurance companies, and received funding from Pneuma Pharmaceuticals.
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