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. DESIGN:: Post hoc analysis of data from a previous randomized, control trial. SETTING:: Tertiary care pediatric intensive care units. PATIENTS:: 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. 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 [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.