A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome1

Surfactant for Pediatric Acute Lung Injury

“…Extracts of minced or homogenized lung tissue (Category II) necessarily contain some non-surfactant components, and require more extensive processing that can further alter composition compared to native surfactant. The synthetic surfactants in Category III that have been most widely studied are Exosurf® and ALEC® (artificial lung expanding compound), although neither of these two preparations is in active clinical use because they have been shown to have inferior activity compared to animal-derived surfactants (e.g., [46,51,[113][114][115][116][117]). Two additional synthetic surfactants, KL4 (Surfaxin®) and recombinant SP-C surfactant (Venticute®), are presently undergoing clinical evaluation, and new synthetic lipid:peptide exogenous surfactants are currently under development.…”

“…Anzueto et al [136] administered nebulized Exosurf® vs. placebo to 725 adults with ARDS secondary to sepsis and found no improvement in any measure of oxygenation and no effect on morbidity or mortality. However, interpretation of these negative results is confounded because both laboratory and clinical studies have documented that Exosurf® has low activity compared to animal-derived surfactants [51, [113][114][115][116][117][142][143][144][145], and aerosolization has not been shown to be as effective as airway instillation in delivering surfactant. Gregory et al [137] reported small benefits in oxygenation in a controlled trial in adults with ARDS who received four 100 mg/kg doses of Survanta®, but with no overall advantage in survival in the 43 surfactant-treated patients studied.…”

Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS

“…They differ in composition, onset of response, and duration of action, dosing volume, and the need for additional doses. Fifteen trials [7][8][9][10][11][12][13][14][15][16][17][18][19][20] comparing natural vs synthetic surfactants (Table 1), 21 and seven studies comparing different natural surfactants have been published (Table 2). 21 Multiple, randomized, controlled trials have consistently shown better clinical outcomes during the acute phase of RDS, and improved survival with natural surfactants than with synthetic surfactants that lack surfactant-associated proteins, especially, surfactant protein-B (SP-B).…”

Synthetic surfactants: where are we? Evidence from randomized, controlled clinical trials

“…[10][11][12][13][14][15] A major advantage of these studies lies in the fact that several thousand infants have been included. A major limitation in the design of these studies is that none of them were masked, except for the comparison included within the lucinactant trial.…”

“…The incidence of these peridosing effects was well within values reported earlier among the few other surfactant comparison trials that have evaluated them. 10,16,17 The STAR (Surfaxin in Therapy Against RDS) trial compared lucinactant with poractant. 23 In this masked study, which was designed as a non-inferiority trial based on data from the only earlier placebo-controlled trial of poractant, the clinical question asked was whether surfactant preparations, one synthetic and one animal-derived, when given in similar concentrations of phospholipids but different amounts of SP-B or its mimic, would result in a clinically meaningful difference in the primary outcome of being alive without BPD at 28 days.…”