lucinactant and dipalmitoylphosphatidylcholine--hexadecanol--tyloxapol-drug-combination

The utilization of multiple natural and synthetic products in surfactant replacement therapies in treatment of neonatal respiratory distress syndrome (NRDS) prompted us to take a closer looks at these various therapeutic options and their efficacies. The purpose of our study was to evaluate the effects of six exogenous pulmonary surfactants (EPS) (Survanta, Alveofact, Infasurf, Curosurf, Surfaxin and Exosurf) on mortality rate in NRDS by a network meta-analysis.. An exhaustive search of electronic databases was performed in PubMed, Ovid, EBSCO, Springerlink, Wiley, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP databases (last updated search in October 2014) to retrieve randomized controlled trials (RCTs) relevant to our study topic. Published clinical trials were screened based on the following inclusion criteria: (1) study design: RCTs; (2) interventions: treatment with Survanta, Alveofact, Infasurf, Curosurf, Surfaxin or Exosurf for NRDS; (3) study subject: infants with NRDS confirmed by clinical diagnosis; (4) outcome: the mortality rate of infants with NRDS. Statistical analysis was performed using Stata 12.0 software (Stata Corporation, College Station, TX, USA) and Comprehensive Meta-analysis (CMA 2.0) software.. From the 1840 studies initially retrieved through database searches, a total of 17 high quality RCTs were selected for this network meta-analysis. The selected studies included a combined total of 57,223 infants with NRDS treated with various EPS (Survanta, 27,017; Alveofact, 159; Infasurf, 20,377; Curosurf, 20,911; Surfaxin, 646; Exosurf, 1640). Network meta-analysis results showed that the mortality rates in NRDS infants treated with Alveofact, Infasurf, Curosurf, Surfaxin, Exosurf were not significantly different compared to Survanta (Alveofact: OR = 1.163, 95% CI = 0.645-2.099, P = 0.616; Infasurf: OR = 0.985, 95% CI = 0.777-1.248, P = 0.897; Curosurf: OR = 0.789, 95% CI = 0.619-1.007, P = 0.056; Surfaxin: OR = 0.728, 95% CI = 0.477-1.112, P = 0.142; Exosurf: OR = 0.960, 95% CI = 0.698-1.319, P = 0.799). Notably, the surface under the cumulative ranking curves (SUCRA) value in Surfaxin group was significantly higher than the other five groups (Surfaxin: 80.4%; Survanta: 37.0%; Alveofact: 24.4%; Infasurf: 40.0%; Curosurf: 73.9%; Exosurf: 44.2%), suggesting that infant mortality rate in Surfaxin group was the lowest among the six EPS groups.. Our study demonstrated that Surfaxin could effectively reduce the mortality rate of infants with NRDS and may have a better efficacy in NRDS treatment, compared to Survanta, Alveofact, Infasurf, Curosurf and Exosurf.

Topics: Biological Products; Drug Combinations; Fatty Alcohols; Humans; Phosphatidylglycerols; Phospholipids; Phosphorylcholine; Polyethylene Glycols; Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn

The benefits of exogenous synthetic or animal-derived surfactants for prevention or treatment of respiratory distress syndrome (RDS) are well established. Data from head-to-head trials comparing animal-derived surfactants primarily with the synthetic surfactant colfosceril suggest that the major clinical advantages afforded by the presence of surfactant protein (SP)-B and SP-C in animal-derived preparations relate to faster onset of action, a reduction in the incidence of RDS when used prophylactically, and a lower incidence of air leaks and RDS-related deaths. However, no benefits in terms of overall mortality or BPD have been shown in these head-to-head comparisons. Findings from trials of a new-generation synthetic surfactant containing a peptide that mimics SP-B, as well as their follow-up study suggest that its administration improves short-term clinical outcomes compared with colfosceril and results in survival through 1 year of age, which is at least comparable, if not perhaps superior, to that seen with animal-derived surfactants.

Topics: Animals; Biological Products; Bronchopulmonary Dysplasia; Dose-Response Relationship, Drug; Drug Combinations; Evidence-Based Medicine; Fatty Alcohols; Follow-Up Studies; Humans; Infant, Newborn; Intensive Care, Neonatal; Phosphatidylglycerols; Phospholipids; Phosphorylcholine; Polyethylene Glycols; Proteins; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Survival Rate; Treatment Outcome

Respiratory distress syndrome (RDS) is a leading cause of mortality and morbidity in preterm infants. Surfactant replacement therapy has been widely used to prevent and treat RDS in these newborns and has now become a standard of care. First-generation synthetic surfactants such as Exosurf did not contain any surfactant protein. This disadvantage was overcome with animal-derived surfactant preparations which contain specific proteins but has the limitation of being derived from animal sources. This has led to development of newer synthetic surfactants such as lucinactant (Surfaxin, Discovery Laboratories, Philadelphia) which contains the protein B mimic synthetic peptide, sinapultide. Recent phase 3 clinical trials with Surfaxin show promising results with similar efficacy as animal derived surfactants and yet avoiding the disadvantage associated with animal products. The purpose of this paper is to summarise results of recent clinical trials of Surfaxin use in newborns with RDS.

Topics: Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Peptides; Phosphatidylglycerols; Phosphorylcholine; Polyethylene Glycols; Polymyxin B; Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Treatment Outcome