Published online June 2, 2008
PEDIATRICS Vol. 121 No. 6 June 2008, pp. 1291-1292 (doi:10.1542/peds.2008-0910)

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LETTER TO THE EDITOR

Surfactant-Replacement Therapy for Respiratory Distress Syndrome in the Preterm and Term Neonate: Congratulations and Corrections: In Reply

William A. Engle, MD
Past Member

Ann R. Stark, MD
Chairperson
AAP Committee on Fetus and Newborn

We are responding to the concerns raised by Moya et al regarding the effects on mortality and morbidity of the novel synthetic surfactant lucinactant compared with animal-derived surfactants (beractant or poractant alfa) as described in the American Academy of Pediatrics Committee on Fetus and Newborn (COFN) clinical report entitled "Surfactant-Replacement Therapy for Respiratory Distress in the Preterm and Term Neonate."¹

In the Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial of RDS in Premature Infants (SELECT) trial, respiratory distress syndrome (RDS) at 24 hours and RDS-related mortality at 14 days, the primary end points, were significantly different.² However, the COFN considered all-cause mortality at 36 weeks' postmenstrual age (PMA), the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks' PMA, and the combined outcome of death or BPD by 36 weeks' PMA to be more clinically relevant end points. Furthermore, the SELECT trial was powered to compare lucinactant and colfosceril, not for comparisons with beractant.² In that trial, the incidence of BPD at 36 weeks' PMA and the combined outcome of death or BPD were not statistically different between the lucinactant and beractant groups, and the comparison of the incidence of death by 36 weeks' PMA had a P value of .051, which was also above the predetermined level of significance.

In the Surfactant Therapy Against RDS (STAR) trial, lucinactant was not inferior to poractant alfa in survival without BPD through 28 days of age.³ The trial was stopped after enrollment of approximately half of the anticipated sample size. All-cause mortality, incidence of BPD, and the combined outcome of mortality or BPD at 36 weeks' PMA were not statistically different. Thus, the COFN concluded that the outcomes after treatment with lucinactant and poractant alfa were similar.

The 1-year follow-up study of patients in the lucinactant trials was not included in the COFN report because it was published during the time interval between manuscript completion and publication of the report.⁴

The animal-derived surfactant preparations commercially available have a well-established 20-year record of safety in thousands of patients. In contrast, lucinactant has proven safe in the short term after administration to 690 preterm infants in 3 clinical trials.^2,3,5 Thus, the COFN thought it was important to raise questions about short-term and long-term safety and efficacy of this drug, which has not yet been approved by the US Food and Drug Administration.

We agree with the investigators that lucinactant is a promising synthetic surfactant that seems to be efficacious and safe. The advantages of synthetic surfactant preparations should compel ongoing efforts to develop lucinactant and other novel surfactants for clinical use.

REFERENCES

1. 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]
2. 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]
3. 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]
4. 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
5. Cochrane CG, Revak SD, Merritt TA, et al. The efficacy and safety of KL4 surfactant in preterm infants with respiratory distress syndrome. Am J Respir Crit Care Med. 1996;153 (1):404 –410[Abstract]

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Engle, W. A. Articles by Stark, A. R. Search for Related Content PubMed Articles by Engle, W. A. Articles by Stark, A. R. Related Collections Premature & Newborn Social Bookmarking                         What's this?