PEDIATRICS Vol. 121 No. 6 June 2008, pp. 1290-1291 (doi:10.1542/peds.2008-0710)
LETTER TO THE EDITOR |
Surfactant-Replacement Therapy for Respiratory Distress Syndrome in the Preterm and Term Neonate: Congratulations and Corrections
Fernando Moya, MDDepartment of Neonatology
Coastal Area Health Education Center
Wilmington, NC 28402
Sunil Sinha, MD, PhD, FRCP, FRCPCH
Department of Pediatrics and Neonatal Medicine
University of Durham and James Cook University Hospital
Middlesbrough TS4 3BN, United Kingdom
Ralph B. D'Agostino, Sr
Department of Mathematics/Statistics and Public Health
Boston University
Boston, MA 02215
To the Editor.—
We would like to express our congratulations to Dr Engle and the American Academy of Pediatrics Committee on Fetus and Newborn on the publication of their clinical report "Surfactant-Replacement Therapy for Respiratory Distress in the Preterm and Term Neonate." Overall, this document was comprehensive in scope yet sufficiently detailed and referenced to provide practical, evidence-based guidance to the clinician who renders neonatal care. However, the attempt to summarize information from so many studies has led to inaccurate statements that, if left uncorrected, are misleading.
The report stated that "[w]hen compared with infants receiving the animal-derived surfactants beractant and poractant alfa, infants receiving lucinactant were found to have similar rates of mortality and morbidity from respiratory distress syndrome [RDS]."1 One of the studies cited in connection with this statement is the Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial of RDS in Premature Infants (SELECT) study.2 The SELECT study, a prospective randomized trial with substantial treatment effects (level of evidence 1), included beractant as a reference comparator to lucinactant for the coprimary end points of RDS at 24 hours and RDS-related mortality through 14 days, for which both end points were adjudicated by an independent blinded adjudication panel. RDS-related mortality through 14 days was 55% less for infants treated with lucinactant compared with beractant (4.7% vs 10.5%, respectively; P = .001). In addition, all-cause mortality through 36 weeks' postmenstrual age was lower in infants treated with lucinactant compared with beractant (21.1% vs 26.4%, respectively; P = .05). Therefore, the statement quoted above and cited in this report by Engle and the Committee on Fetus and Newborn is directly contradictory to the original results of the SELECT trial published in Pediatrics.
Furthermore, we recently reported in Pediatrics on outcomes up to 1 year corrected age for >98% of patients enrolled in the SELECT study and the Surfaxin Therapy Against Respiratory Distress Syndrome (STAR) trial.3 All-cause mortality through 1 year corrected age was significantly lower for infants treated with lucinactant compared with poractant alfa.4 Moreover, in a prospective pooled analysis, all-cause mortality through 1 year corrected age was significantly lower for infants treated with lucinactant compared with animal-derived surfactants. It is unfortunate that these findings, which represent the only published follow-up data from a surfactant comparison trial beyond 36 weeks' postmenstrual age, were not mentioned in the relevant section of this clinical report. However, Engle and the Committee on Fetus and Newborn described correctly that lucinactant did not lower all-cause mortality compared with colfosceril,1 a fact that has also been demonstrated in other trials that compared this first-generation synthetic surfactant to beractant, calfactant, and poractant.5
The additional statement in the clinical report that referred to "early trial closure" and "limited statistical power" does not apply to the SELECT trial, which remains as the largest phase 3 surfactant trial to date. The SELECT study closed only after full prespecified enrollment was attained. This notwithstanding, concerns over statistical power are valid primarily if a small sample size limits the detection of a difference in effect between 
2 therapeutic options. When a statistically significant difference between treatments is detected (as was the case regarding the differences in the coprimary outcomes of incidence of RDS and of its related mortality demonstrated in the SELECT trial), statistical power is not a relevant concern. Raising these issues in connection with the SELECT study suggests that the trial was flawed by these concerns and is, therefore, misleading.
Finally, the statement that "the metabolic fate of lucinactant and its component chemicals and potential risks introduced by the requirement to convert the lucinactant gel into liquid by using a special warming cradle immediately before instillation need additional study" is also misleading. One of the 2 citations referenced to support these statements is only an opinion, without supportive data, contained in an editorial to the other citation referenced, the original publication of the SELECT trial. In fact, published clinical data from RDS trials involving lucinactant suggest that the safety of lucinactant is comparable with that of animal-derived products. Moreover, published evidence suggests that lucinactant has no untoward effects on surfactant protein expression by human fetal type II alveolar cells.6 Therefore, the cautionary statements in this clinical report are not supported by any meaningful level of evidence as defined by the authors themselves.
Given the above-mentioned inaccuracies and the potential clinical import of this clinical report, consideration should be given to publishing an erratum that clarifies or corrects these statements. Doing so would remove the only blemishes on an otherwise excellent and timely clinical report.
REFERENCES
- Engle WA; American Academy of Pediatrics, Committee on Fetus and Newborn. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate.
Pediatrics. 2008;121
(2):419
–432
[Abstract/Free Full Text] - Moya FR, Gadzinowski J, Bancalari E, et al. A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome among very preterm infants.
Pediatrics. 2005;115
(4):1018
–1029
[Abstract/Free Full Text] - Sinha SK, Lacaze-Masmonteil T, Valls I, et al. A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome.
Pediatrics. 2005;115
(4):1030
–1038
[Abstract/Free Full Text] - Moya F, Sinha S, Gadzinowski J, et al. One-year follow-up of very preterm infants who received lucinactant for prevention of respiratory distress syndrome: results from 2 multicenter randomized, controlled trials [published correction appears in Pediatrics. 2007;120(4):935]. Pediatrics. 2007;119 (6). Available at: www.pediatrics.org/cgi/content/full/119/6/e1361
- Moya F, Maturana A. Animal-derived surfactants versus past and current synthetic surfactants: current status. Clin Perinatol. 2007;34 (1):145 –177, viii[CrossRef][Web of Science][Medline]
- Romero EJ, Moya FR, Tuvim MJ, Alcorn JL. Interaction of an artificial surfactant in human pulmonary epithelial cells. Pediatr Pulmonol. 2005;39 (2):167 –177[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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