A pilot randomized, controlled trial of later treatment with a peptide-containing, synthetic surfactant for the prevention of bronchopulmonary dysplasia

Matthew Laughon, Carl Bose, Fernando Moya, Judy L. Aschner, Steven Mark Donn, Christopher Morabito, James John Cummings, Robert Segal, Carlos Guardia, Genzhou Liu

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

OBJECTIVE. Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bron- chopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS. Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of ≥0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS. Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%);no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS. There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation.

Original languageEnglish (US)
Pages (from-to)89-96
Number of pages8
JournalPediatrics
Volume123
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

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Bronchopulmonary Dysplasia
Surface-Active Agents
Randomized Controlled Trials
Placebos
Peptides
Incidence
Phospholipids
Oxygen
Artificial Respiration
Therapeutics
Mortality
Extremely Premature Infants
Periventricular Leukomalacia
Pulmonary Emphysema
Retinopathy of Prematurity
Pneumothorax
Bradycardia
Oxidants
Premature Infants
Pneumonia

Keywords

  • Bronchopulmonary dysplasia
  • Premature infant
  • Surfactant

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

A pilot randomized, controlled trial of later treatment with a peptide-containing, synthetic surfactant for the prevention of bronchopulmonary dysplasia. / Laughon, Matthew; Bose, Carl; Moya, Fernando; Aschner, Judy L.; Donn, Steven Mark; Morabito, Christopher; Cummings, James John; Segal, Robert; Guardia, Carlos; Liu, Genzhou.

In: Pediatrics, Vol. 123, No. 1, 01.2009, p. 89-96.

Research output: Contribution to journalArticle

Laughon, Matthew ; Bose, Carl ; Moya, Fernando ; Aschner, Judy L. ; Donn, Steven Mark ; Morabito, Christopher ; Cummings, James John ; Segal, Robert ; Guardia, Carlos ; Liu, Genzhou. / A pilot randomized, controlled trial of later treatment with a peptide-containing, synthetic surfactant for the prevention of bronchopulmonary dysplasia. In: Pediatrics. 2009 ; Vol. 123, No. 1. pp. 89-96.
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abstract = "OBJECTIVE. Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bron- chopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS. Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of ≥0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS. Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64{\%}) compared with the placebo group (39{\%});no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33{\%}) compared with the placebo group (39{\%}). The incidence of mortality or bronchopulmonary dysplasia was 66{\%} in the placebo group, 79{\%} in the 90 mg/kg group, and 58{\%} in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS. There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation.",
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AU - Donn, Steven Mark

AU - Morabito, Christopher

AU - Cummings, James John

AU - Segal, Robert

AU - Guardia, Carlos

AU - Liu, Genzhou

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N2 - OBJECTIVE. Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bron- chopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS. Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of ≥0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS. Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%);no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS. There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation.

AB - OBJECTIVE. Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bron- chopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS. Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of ≥0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS. Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%);no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS. There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation.

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