Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25–29 weeks' gestation: a randomised trial

Summary

Background

Exogenous surfactant preparations vary in their constitution and biophysical properties. Synthetic and animal-derived preparations lower the rate of death compared with controls. No significant differences in mortality or important long-term clinical outcomes have been shown between them in randomised trials. We did a randomised controlled trial to compare pumactant, a synthetic surfactant, with poractant alfa, an animal-derived surfactant, both of which are widely used in the UK.

Methods

We enrolled 212 neonates born between 25 weeks' and 29 weeks and 6 days' gestation who were intubated for presumed surfactant deficiency and were free from life-threatening malformations. We randomly assigned 105 neonates poractant alfa, and 107 pumactant. The primary outcome was duration of high-dependency care and mortality was a secondary outcome. Analysis was by intention to treat.

Findings

Outcome data were analysed for 199 babies. The trial was stopped on the recommendation of the data and safety monitoring committee because mortality assumed a greater importance than the primary outcome. Predischarge mortality differed significantly between groups, in favour of poractant alfa (14·1 vs 31·0%, p=0·006; odds ratio 0·37 [95% Cl 0·18–0·76). This difference was sustained after adjustment for centre, gestation, birthweight, sex, plurality, and use of antenatal steroids.

Interpretation

Mortality was unexpectedly lower among neonates who received poractant alfa than among those who received pumactant, and was independent of all the variables we investigated. Stopping the trial early may have widened the difference between the treatment groups.

Introduction

The introduction of surfactant treatment has been associated with significantly improved survival in preterm neonates who have neonatal respiratory distress syndrome.1, 2 The effect of combined antenatal steroids and postnatal surfactant is more effective than with either of these treatments alone.³

Surfactants in current use are synthetic or manufactured from animal lung-surfactant extracts (animal-derived or “natural”). Animal-derived surfactants contain a wider variety of phospholipids than do synthetic surfactants, as well as some surfactant-associated proteins. The two types of surfactant significantly reduce morbidity and mortality compared with controls.1, 2 Meta-analyses of randomised controlled trials comparing synthetic and animal-derived surfactants show significantly fewer pulmonary air leaks with animal-derived surfactants.4, 5 One meta-analysis⁴ showed a slightly significant difference in mortality, although this review included non peer-reviewed abstracts, the data from which changed in the final published versions. No other significant differences in clinical outcome were noted in these meta-analyses. Studies included involved comparisons of the synthetic surfactant colfosceril palmitate with the bovine-derived surfactants, beractant or calfactant.

Pumactant is a synthetic surfactant and poractant alfa is a porcine-derived surfactant. These two drugs are commonly used in the UK. In-vitro properties of beractant, colfosceril palmitate, poractant alfa, and pumactant differ.6, 7 Extrapolation of findings from clinical comparisons of colfosceril palmitate against bovine surfactants may not, therefore, reflect outcome differences between pumactant and poractant alfa.

In one animal study, pumactant and adult rabbit surfactant lowered the numbers of pneumothoraces in preterm rabbits compared with controls, but neither treatment had much effect on bronchiolar epithelial damage and hyaline membrane formation.⁸ Five placebo-controlled trials of pumactant have been reported,9, 10, 11, 12, 13 of which two used a preparation similar to that commercially available.12, 13 No published study has, however, compared pumactant with another surfactant in neonates. The only published randomised clinical study comparing poractant alfa with another surfactant (beractant) showed short-term advantages for neonates treated with poractant alfa but no significant differences in any long-term clinical outcomes.¹⁴

We designed a randomised controlled trial to compare pumactant with poractant alfa in neonates. The aim of the study was to investigate whether there was a difference in the cost of treatment with these two surfactants.