Published online May 28, 2007
PEDIATRICS Vol. 119 No. 6 June 2007, pp. e1361-e1370 (doi:10.1542/peds.2006-0149)
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ARTICLE

One-Year Follow-up of Very Preterm Infants Who Received Lucinactant for Prevention of Respiratory Distress Syndrome: Results From 2 Multicenter Randomized, Controlled Trials

Fernando Moya, MDa, Sunil Sinha, MD, PhDb, Janusz Gadzinowski, MD, PhDc,d, Ralph D'Agostino, PhDe, Robert Segal, MDf, Carlos Guardia, MDf, Jan Mazela, MD, PhDc,f, Genzhou Liu, PhDf on behalf of the SELECT and STAR Study Investigators

a Department of Neonatology, Coastal Area Health Education Center, Wilmington, North Carolina
b Department of Pediatrics, James Cook University Hospital, Middlesbrough, United Kingdom
c Department of Neonatology, University of Medical Sciences, Poznan, Poland
d Department of Neonatology, Mother's Memorial Hospital Research Institute, Lodz, Poland
e Department of Mathematics, Boston University, Boston, Massachusetts
f Medical Affairs, Discovery Laboratories, Inc, Warrington, Pennsylvania

BACKGROUND. The benefits of exogenous surfactants for prevention or treatment of respiratory distress syndrome are well established, but there is a paucity of long-term follow-up data from surfactant-comparison trials.

OBJECTIVE. We sought to determine and compare survival and pulmonary and neurodevelopmental outcomes through 1 year corrected age of preterm infants who received lucinactant and other surfactants in the SELECT (Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial) and STAR (Surfaxin Therapy Against Respiratory Distress Syndrome) trials individually and, secondarily, from analysis using combined data from these 2 trials.

METHODS. All infants from both trials who were randomly assigned to administration of lucinactant (175 mg/kg), colfosceril palmitate (67.5 mg/kg), beractant (100 mg/kg), or poractant alfa (175 mg/kg) were prospectively followed through 1 year corrected age, at which point masked assessment of outcomes was performed for surviving infants. One-year survival was a key outcome of interest. Other parameters assessed included rates of rehospitalization and respiratory morbidity and gross neurologic status. Data were analyzed by comparing the different surfactants within each trial and, in secondary analysis, combining data from both trials to compare lucinactant versus the animal-derived surfactants (beractant and poractant) used in these trials. Survival rates over time were compared by using the Wilcoxon test for survival through 1 year corrected age and logistic regression for comparison of fixed time points. The latter analyses were performed by using the prespecified approach, where loss to follow-up or withdrawal of consent was imputed as a death, and also using raw data. Other outcomes were analyzed by using the Cochran-Mantel-Haenszel test or logistic regression for categorical data, and analysis of variance on ranks was used for continuous data.

RESULTS. Very few cases were lost to follow-up in either trial (29 of 1546 enrolled in both trials [1.9%]). In the primary analysis of the SELECT trial comparing lucinactant to either colfosceril or beractant, there were no significant differences in the proportion of infants who were alive through 1 year corrected age. Fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 28.1% for lucinactant, 31.0% for colfosceril, and 31.0% for beractant. By using raw data without imputing loss to follow-up as a death, mortality estimates at 1 year corrected age were computed to be 26.6%, 29.1%, and 28.3%, respectively. In the primary analysis of the STAR trial, significantly more infants treated with lucinactant were alive through 1 year corrected age compared with those who received poractant alfa. Fixed time estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 19.4% for lucinactant and 24.2% for poractant. These estimates using raw data that did not impute loss to follow-up as a death were 18.6% and 21.9%, respectively. In the combined analysis, survival through 1 year corrected age was higher for infants in the lucinactant group versus that of the infants in the animal-derived surfactants (beractant and poractant) group. The fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death for lucinactant and animal-derived surfactants were 26.0% and 29.4%, respectively. However, the 1-year-corrected-age estimates using combined raw data were 24.6% for the lucinactant group and 26.7% for the animal-derived surfactant group. The incidence of postdischarge rehospitalizations, total number of rehospitalizations, incidence of respiratory illnesses, and total number of respiratory illnesses were generally similar among those in the treatment groups. Neurologic status at 1 year corrected age was essentially similar between infants who received lucinactant and those who received all other surfactants used in these 2 trials.

CONCLUSIONS. Findings from this 1-year follow-up of both lucinactant trials indicate that this new peptide-based synthetic surfactant is at least as good, if not superior, to animal-derived surfactants for prevention of respiratory distress syndrome and may be a viable alternative to animal-derived products.

Key Words: long-term survival • respiratory distress syndrome • surfactant • survival rate • 1-year outcome

Abbreviations: RDS—respiratory distress syndrome • SP—surfactant protein • BPD—bronchopulmonary dysplasia • SELECT—Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial • STAR—Surfaxin Therapy Against Respiratory Distress Syndrome • PMA—postmenstrual age • OR—odds ratio • CI—confidence interval

Accepted Mar 1, 2007.