A Randomized, Multicenter Masked Comparison Trial of Poractant Alfa (Curosurf) versus Beractant (Survanta) in the Treatment of Respiratory Distress Syndrome in Preterm Infants

Abstract

We compared the onset of clinical response and safety of two surfactants, poractant alfa (Curosurf, Chiesi Pharmaceuticals, Parma, Italy) and beractant (Survanta, Ross Laboratories, Columbus, OH), for treatment of respiratory distress syndrome (RDS) in preterm infants weighing 750 to 1750 g at birth and <35 weeks gestation. The study was performed as a 20-center prospective, randomized, masked comparison trial. Preterm infants (n = 293) with RDS were randomized to receive an initial dose of either 100 (n = 96) or 200 (n = 99) mg/kg of poractant alfa or 100 ( n = 98) mg/kg of beractant. All repeat dosing was given at 100 mg/kg. The onset of clinical response after the first dose was studied by comparing changes in the fraction of inspired oxygen (F IO(2)) between 0 and 6 hours measured using the area under the curve (F IO(2) AUC (0-6)); other outcomes were assessed for the entire cohort at 28 days and for infants born at < or = 32 weeks gestation at 36 weeks postconceptional age. We found that the mean F IO(2) AUC (0-6) values for the 100 and 200 mg/kg poractant alfa groups were both significantly lower than the mean F IO(2) AUC (0-6) values for the beractant group ( p < 0.005) but were not different from each other. Other outcomes were not different among the three groups for the entire cohort, but in infants born at < or = 32 weeks gestation, mortality up to 36 weeks postconceptional age was significantly less in the 200 mg/kg poractant alfa group than in either the beractant group (3% versus 11%; p = 0.034) or in the 100 mg/kg poractant alfa group (3% versus 11%; p = 0.046). Need for more than one dose of surfactant was significantly lower in infants treated with an initial dose of 200 mg/kg poractant alfa in comparison to the beractant-treated group ( p < 0.002). Treatment with poractant alfa (200 mg/kg initial dose) resulted in rapid reduction in supplemental oxygen with fewer additional doses of surfactant versus treatment with beractant in infants <35 weeks gestation with RDS, and significantly reduced mortality ( p <0.05) than either beractant or poractant alfa (100 mg/kg dosing) in infants < or =32 weeks gestation with RDS.

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

“…Ramanathan et al 25 compared poractant alfa with beractant in a multicenter, randomized, controlled trial in the United States. Treatment with poractant alfa was associated with faster weaning of oxygen, fewer additional doses, and decreased mortality in preterm infants <32 weeks gestation when compared with beractant.…”

“…Cumulatively, 36% of infants randomized to poractant alfa received two or more doses vs 68% in the beractant treated group (P<0.05). In a meta-analysis of the two studies 23,25 comparing beractant vs poractant alfa, neonatal mortality was significantly lower with poractant alfa (odds ratio 0.35, 95% CI 0.13, 0.92). In a recent study comparing these two surfactants, Malloy et al 26 extended the observations of Ramanathan et al 25 They showed improvement in oxygenation to persist up to 48 h ( Figure 1) 26 after treatment with poractant alfa, and a significantly lower number of additional doses with poractant alfa compared to beractant.…”

“…In a meta-analysis of the two studies 23,25 comparing beractant vs poractant alfa, neonatal mortality was significantly lower with poractant alfa (odds ratio 0.35, 95% CI 0.13, 0.92). In a recent study comparing these two surfactants, Malloy et al 26 extended the observations of Ramanathan et al 25 They showed improvement in oxygenation to persist up to 48 h ( Figure 1) 26 after treatment with poractant alfa, and a significantly lower number of additional doses with poractant alfa compared to beractant. It is also interesting to note that the use of a higher initial dose of poractant alfa at 200 mg/kg vs 100 mg/kg of beractant in three comparison trials have consistently shown a lower mortality favoring poractant alfa (Figure 2).…”

“…It is also interesting to note that the use of a higher initial dose of poractant alfa at 200 mg/kg vs 100 mg/kg of beractant in three comparison trials have consistently shown a lower mortality favoring poractant alfa (Figure 2). 23,25,26 This observation may have been due to a larger dose of a more effective surfactant moderating disease severity during the acute phase of RDS in these ill preterm infants, thus resulting in a better survival. However, none of these trials was powered to evaluate mortality as a primary outcome.…”

High frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in respiratory distress syndrome

“…All these factors affect the FiO 2 , oxygenation and the ventilatory requirement especially in the first 24 hours of initial treatment [4,5]. Moreover, text mentions that the lower tidal volumes were targeted in synchronized intermittent mandatory ventilation (SIMV) group but its exact range in mL/kg is missing.…”