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

TOLSURF Study Group

Research output: Contribution to journalArticle

26 Citations (Scopus)

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

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Bronchopulmonary Dysplasia
Premature Infants
Surface-Active Agents
Gestational Age
Nitric Oxide
Lung Diseases
Comorbidity
Newborn Infant
Therapeutics
Control Groups
Artificial Respiration
Birth Weight
Ventilation
Randomized Controlled Trials
Oxygen
Lung
calfactant

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

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Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide. / TOLSURF Study Group.

In: Journal of Pediatrics, Vol. 168, 01.01.2016, p. 23-29.e4.

Research output: Contribution to journalArticle

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title = "Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide",
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.",
author = "{TOLSURF Study Group} and Ballard, {Roberta A.} and Keller, {Roberta L.} and Black, {Dennis M.} and Ballard, {Philip L.} and Merrill, {Jeffrey D.} and Eichenwald, {Eric C.} and Truog, {William E.} and Mammel, {Mark C.} and Steinhorn, {Robin H.} and Rogers, {Elizabeth E.} and Ryan, {Rita M.} and Durand, {David J.} and Asselin, {Jeanette M.} and Bendel, {Catherine M.} and Bendel-Stenzel, {Ellen M.} and Courtney, {Sherry E.} and Ramasubbareddy Dhanireddy and Hudak, {Mark L.} and Koch, {Frances R.} and Mayock, {Dennis E.} and McKay, {Victor J.} and Ramasubbareddy Dhanireddy and Porta, {Nicolas F.} and Rajan Wadhawan and Lisa Palermo and Strong, {S. Hamilton} and J. Immamura-Ching and M. Orfanos-Villalobos and C. Williams and D. Horton and L. Pacello and A. Willard and C. Gauldin and A. Holmes and P. Johnson and K. Meinert and Reynolds, {A. M.} and J. Lucie and P. Conway and M. Leadersdorff and P. Orbank and K. Wynn and M. Deungria and J. Khan and K. Hamann and M. Schau and B. Hopkins and J. Jenson and Mohamad Elabiad and Ajay Talati",
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TY - JOUR

T1 - Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide

AU - TOLSURF Study Group

AU - Ballard, Roberta A.

AU - Keller, Roberta L.

AU - Black, Dennis M.

AU - Ballard, Philip L.

AU - Merrill, Jeffrey D.

AU - Eichenwald, Eric C.

AU - Truog, William E.

AU - Mammel, Mark C.

AU - Steinhorn, Robin H.

AU - Rogers, Elizabeth E.

AU - Ryan, Rita M.

AU - Durand, David J.

AU - Asselin, Jeanette M.

AU - Bendel, Catherine M.

AU - Bendel-Stenzel, Ellen M.

AU - Courtney, Sherry E.

AU - Dhanireddy, Ramasubbareddy

AU - Hudak, Mark L.

AU - Koch, Frances R.

AU - Mayock, Dennis E.

AU - McKay, Victor J.

AU - Dhanireddy, Ramasubbareddy

AU - Porta, Nicolas F.

AU - Wadhawan, Rajan

AU - Palermo, Lisa

AU - Strong, S. Hamilton

AU - Immamura-Ching, J.

AU - Orfanos-Villalobos, M.

AU - Williams, C.

AU - Horton, D.

AU - Pacello, L.

AU - Willard, A.

AU - Gauldin, C.

AU - Holmes, A.

AU - Johnson, P.

AU - Meinert, K.

AU - Reynolds, A. M.

AU - Lucie, J.

AU - Conway, P.

AU - Leadersdorff, M.

AU - Orbank, P.

AU - Wynn, K.

AU - Deungria, M.

AU - Khan, J.

AU - Hamann, K.

AU - Schau, M.

AU - Hopkins, B.

AU - Jenson, J.

AU - Elabiad, Mohamad

AU - Talati, Ajay

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.jpeds.2015.09.031

DO - 10.1016/j.jpeds.2015.09.031

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JF - Journal of Pediatrics

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