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

Abstract

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.

• Authors: Robert F Tamburro, Neal J Thomas, Steven Pon, Brian R Jacobs, Joseph V Dicarlo, Barry P Markovitz, Larry S Jefferson, Douglas F Willson, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
• Journal: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (Pediatr Crit Care Med) Vol. 9 Issue 5 Pg. 459-64 (Sep 2008) ISSN: 1529-7535 [Print] United States
• PMID: 18679142 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biological Products
• Pulmonary Surfactants
• calfactant

Topics

• Acute Lung Injury (drug therapy, physiopathology)
• Adolescent
• Biological Products (administration & dosage, therapeutic use)
• Child
• Clinical Trials as Topic
• Female
• Humans
• Immunocompromised Host
• Male
• Pulmonary Surfactants (administration & dosage, therapeutic use)
• Treatment Outcome