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


METHODS
Post hoc analysis of data from a previous randomized, control trial.


METHODS
Tertiary care pediatric intensive care units.


METHODS
All children, defined as immunocompromised, enrolled in a multicenter, masked, randomized, control trial of calfactant for acute lung injury conducted between July 2000 and July 2003.


METHODS
Patients received either an intratracheal instillation of calfactant or an equal volume of air placebo in a protocolized manner.


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 [CI] -17.3, 37.3). Among the 23 patients with an initial oxygen index (OI) >/=13 and </=37, 44% (4 of 9) of calfactant-treated patients died in comparison with 71% (10 of 14) of placebo (absolute risk reduction 27.0%, 95% CI -13.2, 67.2). Only 33% (3 of 9) of calfactant patients died before intensive care discharge in comparison with 71% (10 of 14) of placebo (absolute risk reduction 38.1%, 95% CI -0.7, 76.9). Calfactant therapy was associated with improved oxygenation in these 23 patients. Using an OI entry criterion of (13 </= OI </= 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, control 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.
Tamburro
Robert F
RF
Department of Pediatrics, Division of Pediatric Critical Care Medicine, Penn State Children's Hospital, The Pennsylvania State University College of Medicine, Hershey, PA, USA. rtamburropsu.edu
Thomas
Neal J
NJ
Pon
Steven
S
Jacobs
Brian R
BR
Dicarlo
Joseph V
JV
Markovitz
Barry P
BP
Jefferson
Larry S
LS
Willson
Douglas F
DF
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D000293:Adolescent; D001688:Biological Products / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D001688:Biological Products; D011663:Pulmonary Surfactants; C117342:calfactant