The marketing of pumactant (Alec), a synthetic surfactant used for treating respiratory distress syndrome in neonates, has been suspended.
The decision was taken by Britannia Pharmaceuticals, the UK manufacturer of pumactant. This followed the early termination of a trial that showed higher mortality in preterm babies given pumactant compared with those given poractant alpha, a porcine-derived surfactant. Britannia Pharmaceuticals says that the finding is unexpected in the light of previously published trials. However, until the implications of the trial results are fully understood, it is voluntarily suspending marketing and distribution of the product with immediate effect and recommends that the product is not used. The company says that stock can be returned for refund.
The trial has been published in the Lancet (2000;355:1387) by Dr Sean Ainsworth (Newcastle neonatal service, Royal Victoria infirmary) and colleagues. A total of 99 babies were given poractant alpha and 100 were given pumactant. Overall, neonatal mortality (defined as death within 28 days) in the two groups was 11 per cent and 25 per cent, respectively. The corresponding figures for predischarge mortality (any death occurring between birth and first discharge) were 14 per cent and 31 per cent. The differences remained significant after adjustment for a number of variables and were consistent across all trial centres, the authors say. The data safety and monitoring committee for the trial, therefore, recommended that the trial be stopped. Dr Ainsworth and colleagues say that, although stopping the trial early may have widened the difference between the two treatment groups, the findings "have implications for clinical practice".
Dr Alan Jobe (division of pulmonary biology, Children's hospital medical centre, Cincinnati, US) considers possible explanations for the results in a commentary on the paper (ibid, p1380). One possibility is that the synthetic surfactant was less effective because of the method of administration, which may have favoured the natural surfactant. In animal models, "strikingly different" responses have been obtained according to the positive end-expiratory pressure used to ventilate the animal, he explains. Information on the ventilation strategy used in this trial was not given. Dr Jobe concludes that this trial, together with previous meta-analyses, shows that animal-source surfactants have a "consistent advantage" over the currently available synthetic products.