Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide

TOLSURF Study Group

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Objective To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Study design Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. Results A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P =.89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P =.33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. Conclusion Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. Trial registration ClinicalTrials.gov: NCT01022580.

Original languageEnglish (US)
Pages (from-to)23-29.e4
JournalJournal of Pediatrics
Volume168
DOIs
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
Supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (U01-HL094338 and U01HL094355) and the UCSF Clinical and Translational Sciences Institute (UL1TR000004). ONY, Inc provided the Infasurf and IKARIA, Inc provided the inhaled nitric oxide, neither of which were involved in study design, collection, analysis, or interpretation of data, writing the manuscript or the decision to submit for publication. The authors declare no conflicts of interest. We thank Nancy Newton, MS, RN, CCRP, the project director for the first 4 years of the trial; Karin L. Knowles, for managing the administrative and regulatory aspects of the study and for help with preparation of the manuscript; the neonatal nurses, nurse practitioners, residents, fellows, and respiratory therapists who made this study possible; and to the families and infants who participated in the study.

Funding Information:
Supported by the National Institutes of Health / National Heart, Lung, and Blood Institute ( U01-HL094338 and U01HL094355 ) and the UCSF Clinical and Translational Sciences Institute ( UL1TR000004 ). ONY, Inc provided the Infasurf and IKARIA, Inc provided the inhaled nitric oxide, neither of which were involved in study design, collection, analysis, or interpretation of data, writing the manuscript or the decision to submit for publication. The authors declare no conflicts of interest.

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