Post hoc analysis of calfactant use in immunocompromised children with acute lung injury: Impact and feasibility of further clinical trials.

Author(s): Tamburro RF, Thomas NJ, Pon S, Jacobs BR, Dicarlo JV, Markovitz BP, Jefferson LS, Willson DF, for the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network

Affiliation(s): From the Department of Pediatrics (RFT, NJT), Division of Pediatric Critical Care Medicine, Penn State Children's Hospital, The Pennsylvania State University College of Medicine, Hershey, PA; Department of Public Health Sciences (RFT, NJT), Penn State Children's Hospital, The Pennsylvania State University College of Medicine, Hershey, PA; Department of Pediatrics (SP), Division of Pediatric Critical Care Medicine, Cornell University, New York, NY; Division of Pediatric Critical Care Medicine (BRJ), Children's National Medical Center, Washington DC; Department of Pediatrics (JVD), Division of Pediatric Critical Care Medicine, Stanford University, Palo Alto, CA; Department of Anesthesiology Critical Care Medicine (BPM), Division of Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA; Department of Pediatrics (LSJ), Section of Critical Care Medicine, Baylor College of Medicine, Houston, TX; and Department of Pediatrics (DFW), Division of Pediatric Critical Care Medicine, University of Virginia, Charlottesville, VA.

Publication date & source: 2008-08-01, Pediatr Crit Care Med., [Epub ahead of print]

Publication type:

OBJECTIVE:: To assess the impact of calfactant (a modified natural bovine lung surfactant) in immunocompromised children with acute lung injury and to determine the number of patients required for a definitive clinical trial of calfactant in this population. DESIGN:: Post hoc analysis of data from a previous randomized, controlled trial. SETTING:: Tertiary care pediatric intensive care units. PATIENTS:: All children, defined as immunocompromised, enrolled in a multicenter, masked, randomized, controlled trial of calfactant for acute lung injury conducted between July 2000 and July 2003. INTERVENTIONS:: Patients received either an intratracheal instillation of calfactant or an equal volume of air placebo in a protocolized manner. MEASUREMENTS AND MAIN RESULTS:: Eleven of 22 (50%) calfactant-treated patients died when compared with 18 of 30 (60%) placebo patients (absolute risk reduction 10.0%, 95% confidence interval -17.3-37.3). Among the 23 patients with an initial oxygen index >/=13 and </=37, 44% (4/9) of calfactant-treated patients died in comparison with 71% (10/14) of placebo (absolute risk reduction 27.0%, 95% confidence interval -13.2-67.2). Only 33% (3/9) of calfactant patients died before intensive care discharge in comparison with 71% (10/14) of placebo (absolute risk reduction 38.1%, 95% confidence interval -0.7-76.9). Calfactant therapy was associated with improved oxygenation in these 23 patients. Using an oxygen index entry criterion of (13 </= oxygen index </= 37), stratifying on the presence of hematopoietic stem cell transplantation, and accepting the 27% difference in mortality observed in this analysis, 63 patients would be required in each arm of a randomized, controlled trial to demonstrate a significant effect of calfactant on mortality in this patient population assuming a two-sided alpha of 0.05 and a power of 0.85. CONCLUSIONS:: These preliminary data suggest a potential benefit of calfactant in this high-risk population. A clinical trial powered to appropriately assess these findings seems warranted and feasible.