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Thomas H Shaffer - One of the best experts on this subject based on the ideXlab platform.
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Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS
Pediatric Research, 2012Co-Authors: Marla R. Wolfson, Timothy J. Gregory, Jan Mazela, Terrence L. Hubert, Thomas H ShafferAbstract:Background: Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL_4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Methods: Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, Beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. Results: SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or Beractant. Conclusion: These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or Beractant.
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KL_4-Surfactant (Lucinactant) Protects Human Airway Epithelium from Hyperoxia
Pediatric Research, 2008Co-Authors: Yan Zhu, Thomas L Miller, Aaron Chidekel, Thomas H ShafferAbstract:Exogenous surfactant is critical in the treatment of neonates with respiratory distress syndrome. Lucinactant (Surfaxin; Discovery Laboratories, Inc.) is a surfactant replacement therapy containing sinulpeptide, which may reduce lung inflammation. This study tested whether Lucinactant reduces markers of inflammation, damage and remodeling in human airway epithelial cells exposed to hyperoxia. Calu-3 monolayers cultured at an air–liquid interface were treated apically with 140 μL of normal saline, Lucinactant or Beractant (Survanta; Abbott Laboratories, Inc.). Treated monolayers were exposed to 60% O_2/5% CO_2 for 24 or 72 h. Transepithelial resistance (TER; p < 0.001) and cell viability ( p < 0.05) were greater in both surfactant groups compared with saline; by 72 h Lucinactant cells had greater TER than Beractant ( p < 0.001). Surfactant treated groups secreted less IL-8 than saline ( p < 0.001), whereas Lucinactant cells secreted less IL-6 than saline and Beractant ( p < 0.001). Matrix metalloproteinase 7, expressed by saline and Beractant treated cells at 24 h, was attenuated by 72 h by Beractant ( p < 0.001), but was never detected in Lucinactant cells. Histology indicated less injury with Lucinactant relative to Beractant and saline. These data suggest that Lucinactant was protective compared with Beractant and control.
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KL4-surfactant (Lucinactant) protects human airway epithelium from hyperoxia.
Pediatric research, 2008Co-Authors: Yan Zhu, Thomas L Miller, Aaron Chidekel, Thomas H ShafferAbstract:Exogenous surfactant is critical in the treatment of neonates with respiratory distress syndrome. Lucinactant (Surfaxin; Discovery Laboratories, Inc.) is a surfactant replacement therapy containing sinulpeptide, which may reduce lung inflammation. This study tested whether Lucinactant reduces markers of inflammation, damage and remodeling in human airway epithelial cells exposed to hyperoxia. Calu-3 monolayers cultured at an air–liquid interface were treated apically with 140 μL of normal saline, Lucinactant or Beractant (Survanta; Abbott Laboratories, Inc.). Treated monolayers were exposed to 60% O2/5% CO2 for 24 or 72 h. Transepithelial resistance (TER; p < 0.001) and cell viability (p < 0.05) were greater in both surfactant groups compared with saline; by 72 h Lucinactant cells had greater TER than Beractant (p < 0.001). Surfactant treated groups secreted less IL-8 than saline (p < 0.001), whereas Lucinactant cells secreted less IL-6 than saline and Beractant (p < 0.001). Matrix metalloproteinase 7, expressed by saline and Beractant treated cells at 24 h, was attenuated by 72 h by Beractant (p < 0.001), but was never detected in Lucinactant cells. Histology indicated less injury with Lucinactant relative to Beractant and saline. These data suggest that Lucinactant was protective compared with Beractant and control.
Kristin Viswanathan - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of porcine versus bovine surfactants for preterm newborns with respiratory distress syndrome: systematic review and meta-analysis.
Pediatrics, 2011Co-Authors: Neetu Singh, Kristy L Hawley, Kristin ViswanathanAbstract:OBJECTIVE: To compare the efficacy of a porcine surfactant (poractant alfa) versus bovine surfactants (Beractant and calfactant) with respect to clinical outcomes among preterm infants with respiratory distress syndrome. METHODS: A search of major electronic databases, including Medline (1980–2010) and the Cochrane Central Register of Controlled Trials, for randomized controlled trials that compared poractant alfa versus Beractant and/or calfactant among preterm infants with respiratory distress syndrome who required intubation and surfactant treatment was performed. The primary outcome was oxygen requirement at a postmenstrual age of 36 weeks. RESULTS: Five randomized controlled trials involving 529 infants compared poractant alfa versus Beractant for rescue treatment. No trials studied surfactant prophylaxis, and none compared poractant alfa versus calfactant. The incidences of oxygen dependence at a postmenstrual age of 36 weeks were similar for poractant alfa and Beractant. Infants treated with poractant alfa at 100 mg/kg (low dose) or 200 mg/kg (high dose) exhibited statistically significant reductions in deaths (relative risk: 0.51 [95% confidence interval: 0.30–0.89]), the need for redosing (relative risk: 0.71 [95% confidence interval: 0.57–0.88]), oxygen requirements, duration of oxygen treatment, and duration of mechanical ventilation. The test of heterogeneity yielded positive results for the latter 2 outcomes. The difference remained statistically significant for deaths and the need for redosing with high-dose poractant alfa but not for low dose poractant alfa. CONCLUSIONS: There were significant reductions in deaths and the need for redosing with high-dose poractant alfa but not low-dose poractant alfa, compared with Beractant.
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Efficacy of porcine versus bovine surfactants for preterm newborns with respiratory distress syndrome: systematic review and meta-analysis.
Pediatrics, 2011Co-Authors: Neetu Singh, Kristy L Hawley, Kristin ViswanathanAbstract:To compare the efficacy of a porcine surfactant (poractant alfa) versus bovine surfactants (Beractant and calfactant) with respect to clinical outcomes among preterm infants with respiratory distress syndrome. A search of major electronic databases, including Medline (1980-2010) and the Cochrane Central Register of Controlled Trials, for randomized controlled trials that compared poractant alfa versus Beractant and/or calfactant among preterm infants with respiratory distress syndrome who required intubation and surfactant treatment was performed. The primary outcome was oxygen requirement at a postmenstrual age of 36 weeks. Five randomized controlled trials involving 529 infants compared poractant alfa versus Beractant for rescue treatment. No trials studied surfactant prophylaxis, and none compared poractant alfa versus calfactant. The incidences of oxygen dependence at a postmenstrual age of 36 weeks were similar for poractant alfa and Beractant. Infants treated with poractant alfa at 100 mg/kg (low dose) or 200 mg/kg (high dose) exhibited statistically significant reductions in deaths (relative risk: 0.51 [95% confidence interval: 0.30-0.89]), the need for redosing (relative risk: 0.71 [95% confidence interval: 0.57-0.88]), oxygen requirements, duration of oxygen treatment, and duration of mechanical ventilation. The test of heterogeneity yielded positive results for the latter 2 outcomes. The difference remained statistically significant for deaths and the need for redosing with high-dose poractant alfa but not for low dose poractant alfa. There were significant reductions in deaths and the need for redosing with high-dose poractant alfa but not low-dose poractant alfa, compared with Beractant.
Robert Segal - One of the best experts on this subject based on the ideXlab platform.
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Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy
Journal of Neonatal-Perinatal Medicine, 2011Co-Authors: Carlos Guardia, Fernando R. Moya, Phillip D. Simmons, Janusz Gadzinowski, Sunil K Sinha, Steven M. Donn, Robert SegalAbstract:Background: In preterm infants at risk for RDS, reintubation following surfactant replacement therapy and successful extubation may be associated with poor clinical outcomes. Methods: Initial extubation, reintubation, mortality, and major morbidity rates associated with prematurity from two surfactant trials utilizing lucinactant, colfosceril palmitate, Beractant, and poractant alfa were compared for reintubated infants versus infants who were not reintubated, and among treatment groups.
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One-year follow-up of very preterm infants who received lucinactant for prevention of respiratory distress syndrome: results from 2 multicenter randomized, controlled trials.
Pediatrics, 2007Co-Authors: Fernando R. Moya, Jan Mazela, Carlos Guardia, Robert Segal, Janusz Gadzinowski, Sunil K Sinha, Ralph B. D'agostino, Genzhou LiuAbstract:BACKGROUND The benefits of exogenous surfactants for prevention or treatment of respiratory distress syndrome are well established, but there is a paucity of long-term follow-up data from surfactant-comparison trials. OBJECTIVE We sought to determine and compare survival and pulmonary and neurodevelopmental outcomes through 1 year corrected age of preterm infants who received lucinactant and other surfactants in the SELECT (Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial) and STAR (Surfaxin Therapy Against Respiratory Distress Syndrome) trials individually and, secondarily, from analysis using combined data from these 2 trials. METHODS All infants from both trials who were randomly assigned to administration of lucinactant (175 mg/kg), colfosceril palmitate (67.5 mg/kg), Beractant (100 mg/kg), or poractant alfa (175 mg/kg) were prospectively followed through 1 year corrected age, at which point masked assessment of outcomes was performed for surviving infants. One-year survival was a key outcome of interest. Other parameters assessed included rates of rehospitalization and respiratory morbidity and gross neurologic status. Data were analyzed by comparing the different surfactants within each trial and, in secondary analysis, combining data from both trials to compare lucinactant versus the animal-derived surfactants (Beractant and poractant) used in these trials. Survival rates over time were compared by using the Wilcoxon test for survival through 1 year corrected age and logistic regression for comparison of fixed time points. The latter analyses were performed by using the prespecified approach, where loss to follow-up or withdrawal of consent was imputed as a death, and also using raw data. Other outcomes were analyzed by using the Cochran-Mantel-Haenszel test or logistic regression for categorical data, and analysis of variance on ranks was used for continuous data. RESULTS Very few cases were lost to follow-up in either trial (29 of 1546 enrolled in both trials [1.9%]). In the primary analysis of the SELECT trial comparing lucinactant to either colfosceril or Beractant, there were no significant differences in the proportion of infants who were alive through 1 year corrected age. Fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 28.1% for lucinactant, 31.0% for colfosceril, and 31.0% for Beractant. By using raw data without imputing loss to follow-up as a death, mortality estimates at 1 year corrected age were computed to be 26.6%, 29.1%, and 28.3%, respectively. In the primary analysis of the STAR trial, significantly more infants treated with lucinactant were alive through 1 year corrected age compared with those who received poractant alfa. Fixed time estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 19.4% for lucinactant and 24.2% for poractant. These estimates using raw data that did not impute loss to follow-up as a death were 18.6% and 21.9%, respectively. In the combined analysis, survival through 1 year corrected age was higher for infants in the lucinactant group versus that of the infants in the animal-derived surfactants (Beractant and poractant) group. The fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death for lucinactant and animal-derived surfactants were 26.0% and 29.4%, respectively. However, the 1-year-corrected-age estimates using combined raw data were 24.6% for the lucinactant group and 26.7% for the animal-derived surfactant group. The incidence of postdischarge rehospitalizations, total number of rehospitalizations, incidence of respiratory illnesses, and total number of respiratory illnesses were generally similar among those in the treatment groups. Neurologic status at 1 year corrected age was essentially similar between infants who received lucinactant and those who received all other surfactants used in these 2 trials. CONCLUSIONS Findings from this 1-year follow-up of both lucinactant trials indicate that this new peptide-based synthetic surfactant is at least as good, if not superior, to animal-derived surfactants for prevention of respiratory distress syndrome and may be a viable alternative to animal-derived products.
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KL4-surfactant prevents hyperoxic and LPS-induced lung injury in mice
Pediatric pulmonology, 2006Co-Authors: Paul A. Kinniry, Robert Segal, Jeremy Pick, Scott Stephens, Deepika Jain, Charalambos C. Solomides, Ralph Niven, Melpo Christofidou-solomidouAbstract:KL4-surfactant contains the novel KL4 peptide, sinapultide, which mimics properties of the hydrophobic pulmonary surfactant protein SP-B, in a phospholipid formulation and may be lung protective in experimental acute respiratory distress syndrome/acute lung injury. Our objective was to determine the protective role of airway delivery of KL4-surfactant in murine models of hyperoxic and lipopolysaccharide (LPS)-induced lung injury and further explore the mechanisms of protection. For the hyperoxic injury model, mice exposed to 80% O2 for 6 days received an intranasal bolus of vehicle, Beractant, or KL4-surfactant on days 3, 4, 5, and 6 of the exposure, and lungs were evaluated on day 7. Mice in the LPS-induced lung injury model received an intratracheal bolus of LPS followed by an intranasal bolus of KL4-surfactant or control at 1, 3, and 19 hr post-LPS challenge, and lungs were evaluated after 24 hr. To explore the mechanisms of protection, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL4-surfactant or lipid controls was evaluated. Based on morphology, histopathology, white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, our data showed KL4-surfactant, unlike vehicle or Beractant, blocked neutrophil influx into alveoli and suppressed lung injury. Furthermore, in vitro assays showed KL4-surfactant decreased neutrophil transmigration at the endothelial cell level. KL4-surfactant decreased inflammation and lung permeability compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL4-peptide is through inhibition of PMN transmigration through the endothelium. Pediatr Pulmonol. 2006, 41:916–928. © 2006 Wiley-Liss, Inc.
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a multicenter randomized masked comparison trial of lucinactant colfosceril palmitate and Beractant for the prevention of respiratory distress syndrome among very preterm infants
Pediatrics, 2005Co-Authors: Fernando R. Moya, Robert Segal, Janusz Gadzinowski, Eduardo Bancalari, Vicente Salinas, Benjamin Kopelman, Aldo Bancalari, M K Kornacka, Allen T Merritt, Christopher SchaberAbstract:Background and Objective. Evidence sug- gests that synthetic surfactants consisting solely of phos- pholipids can be improved through the addition of pep- tides, such as sinapultide, that mimic the action of hu- man surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived sur- factant (Beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syn- drome (RDS) and RDS-related death. Methods. We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of <32 weeks gestational age, to receive colfosceril palmi- tate (n 509), lucinactant (n 527), or Beractant (n 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dys- plasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Pri- mary outcomes, air leaks, and causes of death were as- signed by an independent, masked, adjudication com- mittee with prespecified definitions. The study was monitored by an independent data safety monitoring board. Results. Lucinactant reduced significantly the inci- dence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio (OR): 0.68; 95% confidence interval (CI): 0.52-0.89). There was no significant differ- ence in comparison with Beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and Beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less com- mon with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with Beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). Conclusions. Lucinactant is a more effective surfac- tant preparation than colfosceril palmitate for the pre- vention of RDS. In addition, lucinactant reduces the in- cidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with Beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS. Pediatrics 2005;115: 1018-1029; lucinactant, colfosceril palmitate, Beractant, surfactant, respiratory distress syndrome.
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a multicenter randomized masked comparison trial of lucinactant colfosceril palmitate and Beractant for the prevention of respiratory distress syndrome among very preterm infants
Pediatrics, 2005Co-Authors: Fernando R. Moya, Robert Segal, Janusz Gadzinowski, Eduardo Bancalari, Vicente Salinas, Benjamin Kopelman, Aldo Bancalari, M K Kornacka, Allen T Merritt, Christopher SchaberAbstract:Background and Objective. Evidence sug- gests that synthetic surfactants consisting solely of phos- pholipids can be improved through the addition of pep- tides, such as sinapultide, that mimic the action of hu- man surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived sur- factant (Beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syn- drome (RDS) and RDS-related death. Methods. We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of <32 weeks gestational age, to receive colfosceril palmi- tate (n 509), lucinactant (n 527), or Beractant (n 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dys- plasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Pri- mary outcomes, air leaks, and causes of death were as- signed by an independent, masked, adjudication com- mittee with prespecified definitions. The study was monitored by an independent data safety monitoring board. Results. Lucinactant reduced significantly the inci- dence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio (OR): 0.68; 95% confidence interval (CI): 0.52-0.89). There was no significant differ- ence in comparison with Beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and Beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less com- mon with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with Beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). Conclusions. Lucinactant is a more effective surfac- tant preparation than colfosceril palmitate for the pre- vention of RDS. In addition, lucinactant reduces the in- cidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with Beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS. Pediatrics 2005;115: 1018-1029; lucinactant, colfosceril palmitate, Beractant, surfactant, respiratory distress syndrome.
Fernando R. Moya - One of the best experts on this subject based on the ideXlab platform.
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Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy
Journal of Neonatal-Perinatal Medicine, 2011Co-Authors: Carlos Guardia, Fernando R. Moya, Phillip D. Simmons, Janusz Gadzinowski, Sunil K Sinha, Steven M. Donn, Robert SegalAbstract:Background: In preterm infants at risk for RDS, reintubation following surfactant replacement therapy and successful extubation may be associated with poor clinical outcomes. Methods: Initial extubation, reintubation, mortality, and major morbidity rates associated with prematurity from two surfactant trials utilizing lucinactant, colfosceril palmitate, Beractant, and poractant alfa were compared for reintubated infants versus infants who were not reintubated, and among treatment groups.
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Animal-derived surfactants for the treatment and prevention of neonatal respiratory distress syndrome: summary of clinical trials
Therapeutics and clinical risk management, 2009Co-Authors: J. Wells Logan, Fernando R. MoyaAbstract:INTRODUCTION Available literature suggests that the advantage of animal-derived surfactants over first-generation synthetic agents derives from the presence of surface-active proteins and their phospholipid content. Here we summarize the results of clinical trials comparing animal-derived surfactant preparations with other animal-derived surfactants and with both first-and second-generation synthetic surfactants. METHODS Published clinical trials of comparisons of animal-derived surfactants were summarized and compared. Comparisons emphasized differences in (1) key surfactant components attributed with efficacy and (2) differences in published outcomes. RESULTS For the most important outcomes, mortality and chronic lung disease, currently available natural surfactants are essentially similar in efficacy. When examining secondary outcomes (pneumothorax, ventilator weaning, and need for supplemental oxygen), it appears that both calfactant and poractant have an advantage over Beractant. The weight of the evidence, especially for study design and secondary outcomes, favors the use of calfactant. However, the superiority of poractant over Beractant, when the higher initial dose of poractant is used, strengthens the case for use of poractant as well. CONCLUSIONS Clinical trials suggest that the higher surfactant protein-B content in calfactant, and perhaps the higher phospholipid content in poractant (at higher initial dose), are the factors that most likely confer the observed advantage over other surfactant preparations.
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Animal-derived surfactants for the treatment and prevention of neonatal respiratory distress syndrome: summary of clinical trials
Dove Medical Press, 2009Co-Authors: Wells J Logan, Fernando R. MoyaAbstract:J Wells Logan, Fernando R MoyaDepartment of Neonatology, Southeast Area Health Educational Center, New Hanover Regional Medical Center, Wilmington, NC, USAIntroduction: Available literature suggests that the advantage of animal-derived surfactants over first-generation synthetic agents derives from the presence of surface-active proteins and their phospholipid content. Here we summarize the results of clinical trials comparing animal-derived surfactant preparations with other animal-derived surfactants and with both first- and second-generation synthetic surfactants.Methods: Published clinical trials of comparisons of animal-derived surfactants were summarized and compared. Comparisons emphasized differences in (1) key surfactant components attributed with efficacy and (2) differences in published outcomes.Results: For the most important outcomes, mortality and chronic lung disease, currently available natural surfactants are essentially similar in efficacy. When examining secondary outcomes (pneumothorax, ventilator weaning, and need for supplemental oxygen), it appears that both calfactant and poractant have an advantage over Beractant. The weight of the evidence, especially for study design and secondary outcomes, favors the use of calfactant. However, the superiority of poractant over Beractant, when the higher initial dose of poractant is used, strengthens the case for use of poractant as well.Conclusions: Clinical trials suggest that the higher surfactant protein-B content in calfactant, and perhaps the higher phospholipid content in poractant (at higher initial dose), are the factors that most likely confer the observed advantage over other surfactant preparations. Keywords: surfactant, respiratory distress syndrome, phospholipids, surfactant proteins, chronic lung disease, bronchopulmonary dysplasi
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One-year follow-up of very preterm infants who received lucinactant for prevention of respiratory distress syndrome: results from 2 multicenter randomized, controlled trials.
Pediatrics, 2007Co-Authors: Fernando R. Moya, Jan Mazela, Carlos Guardia, Robert Segal, Janusz Gadzinowski, Sunil K Sinha, Ralph B. D'agostino, Genzhou LiuAbstract:BACKGROUND The benefits of exogenous surfactants for prevention or treatment of respiratory distress syndrome are well established, but there is a paucity of long-term follow-up data from surfactant-comparison trials. OBJECTIVE We sought to determine and compare survival and pulmonary and neurodevelopmental outcomes through 1 year corrected age of preterm infants who received lucinactant and other surfactants in the SELECT (Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial) and STAR (Surfaxin Therapy Against Respiratory Distress Syndrome) trials individually and, secondarily, from analysis using combined data from these 2 trials. METHODS All infants from both trials who were randomly assigned to administration of lucinactant (175 mg/kg), colfosceril palmitate (67.5 mg/kg), Beractant (100 mg/kg), or poractant alfa (175 mg/kg) were prospectively followed through 1 year corrected age, at which point masked assessment of outcomes was performed for surviving infants. One-year survival was a key outcome of interest. Other parameters assessed included rates of rehospitalization and respiratory morbidity and gross neurologic status. Data were analyzed by comparing the different surfactants within each trial and, in secondary analysis, combining data from both trials to compare lucinactant versus the animal-derived surfactants (Beractant and poractant) used in these trials. Survival rates over time were compared by using the Wilcoxon test for survival through 1 year corrected age and logistic regression for comparison of fixed time points. The latter analyses were performed by using the prespecified approach, where loss to follow-up or withdrawal of consent was imputed as a death, and also using raw data. Other outcomes were analyzed by using the Cochran-Mantel-Haenszel test or logistic regression for categorical data, and analysis of variance on ranks was used for continuous data. RESULTS Very few cases were lost to follow-up in either trial (29 of 1546 enrolled in both trials [1.9%]). In the primary analysis of the SELECT trial comparing lucinactant to either colfosceril or Beractant, there were no significant differences in the proportion of infants who were alive through 1 year corrected age. Fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 28.1% for lucinactant, 31.0% for colfosceril, and 31.0% for Beractant. By using raw data without imputing loss to follow-up as a death, mortality estimates at 1 year corrected age were computed to be 26.6%, 29.1%, and 28.3%, respectively. In the primary analysis of the STAR trial, significantly more infants treated with lucinactant were alive through 1 year corrected age compared with those who received poractant alfa. Fixed time estimates of mortality at 1 year corrected age imputing loss to follow-up as a death were 19.4% for lucinactant and 24.2% for poractant. These estimates using raw data that did not impute loss to follow-up as a death were 18.6% and 21.9%, respectively. In the combined analysis, survival through 1 year corrected age was higher for infants in the lucinactant group versus that of the infants in the animal-derived surfactants (Beractant and poractant) group. The fixed-time-point estimates of mortality at 1 year corrected age imputing loss to follow-up as a death for lucinactant and animal-derived surfactants were 26.0% and 29.4%, respectively. However, the 1-year-corrected-age estimates using combined raw data were 24.6% for the lucinactant group and 26.7% for the animal-derived surfactant group. The incidence of postdischarge rehospitalizations, total number of rehospitalizations, incidence of respiratory illnesses, and total number of respiratory illnesses were generally similar among those in the treatment groups. Neurologic status at 1 year corrected age was essentially similar between infants who received lucinactant and those who received all other surfactants used in these 2 trials. CONCLUSIONS Findings from this 1-year follow-up of both lucinactant trials indicate that this new peptide-based synthetic surfactant is at least as good, if not superior, to animal-derived surfactants for prevention of respiratory distress syndrome and may be a viable alternative to animal-derived products.
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a multicenter randomized masked comparison trial of lucinactant colfosceril palmitate and Beractant for the prevention of respiratory distress syndrome among very preterm infants
Pediatrics, 2005Co-Authors: Fernando R. Moya, Robert Segal, Janusz Gadzinowski, Eduardo Bancalari, Vicente Salinas, Benjamin Kopelman, Aldo Bancalari, M K Kornacka, Allen T Merritt, Christopher SchaberAbstract:Background and Objective. Evidence sug- gests that synthetic surfactants consisting solely of phos- pholipids can be improved through the addition of pep- tides, such as sinapultide, that mimic the action of hu- man surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived sur- factant (Beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syn- drome (RDS) and RDS-related death. Methods. We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of <32 weeks gestational age, to receive colfosceril palmi- tate (n 509), lucinactant (n 527), or Beractant (n 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dys- plasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Pri- mary outcomes, air leaks, and causes of death were as- signed by an independent, masked, adjudication com- mittee with prespecified definitions. The study was monitored by an independent data safety monitoring board. Results. Lucinactant reduced significantly the inci- dence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio (OR): 0.68; 95% confidence interval (CI): 0.52-0.89). There was no significant differ- ence in comparison with Beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and Beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less com- mon with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with Beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). Conclusions. Lucinactant is a more effective surfac- tant preparation than colfosceril palmitate for the pre- vention of RDS. In addition, lucinactant reduces the in- cidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with Beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS. Pediatrics 2005;115: 1018-1029; lucinactant, colfosceril palmitate, Beractant, surfactant, respiratory distress syndrome.
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Multicenter study of surfactant (Beractant) use in the treatment of term infants with severe respiratory failure
The Journal of pediatrics, 1998Co-Authors: Andrea Lotze, Elizabeth M. Zola, Brian R. Mitchell, Dorothy I Bulas, Robert A. Shalwitz, J. Harry GunkelAbstract:Abstract Objective: The purpose of this study was to determine whether surfactant (Beractant) administration to term newborns in respiratory failure and at risk for requiring extracorporeal membrane oxygenation (ECMO) treatment would significantly reduce the incidence of severe complications through 28 days of age and the need for ECMO. Study design: A multicenter ( n = 44), randomized, double-blind, placebo-controlled trial was conducted. Infants weighing 2000 gm or more with gestational ages of 36 weeks or greater were stratified by diagnosis (meconium aspiration syndrome, sepsis, or idiopathic persistent pulmonary hypertension of the newborn) and oxygenation index (15 to 22, 23 to 30, 31 to 39) and then randomly assigned to receive four doses of Beractant, 100 mg/kg ( n = 167), or air placebo ( n = 161) before ECMO treatment and four additional doses during ECMO, if ECMO was required. The incidence of untoward effects (including hemorrhagic, neurologic, pulmonary, renal, cardiovascular, infectious, metabolic, and technical complications) occurring before and after randomization and through 28 days of age or discharge were recorded. Results: The two treatment groups were comparable in baseline parameters, including birth weight, sex, gestational age, oxygenation index, and primary diagnosis. There was no difference in the incidence of severe complications. The need for ECMO therapy was significantly less in the surfactant group than in the placebo group ( p = 0.038); this effect was greatest within the lowest oxygenation index stratum (15 to 22; p = 0.013). Conclusions: Use of surfactant, particularly in the early phase of respiratory failure, significantly decreases the need for ECMO in the treatment of term newborns with respiratory failure, without increasing the risk of complications. (J Pediatr 1998;132:40-7)
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improved pulmonary outcome after exogenous surfactant therapy for respiratory failure in term infants requiring extracorporeal membrane oxygenation
The Journal of Pediatrics, 1993Co-Authors: Andrea Lotze, Gail R Knight, Gerard R Martin, Dorothy I BulasAbstract:A blinded, randomized, controlled study was designed to test whether multiple-dose surfactant therapy would improve pulmonary outcome in term infants with respiratory failure, resulting in a shortened period of extracorporeal membrane oxygenation (ECMO). Infants≥34 weeks of gestational age in severe respiratory failure and receiving ECMO were stratified by diagnosis and then randomly assigned to the treatment or the control group. Four doses of modified bovine lung surfactant extract (Beractant) were administered to the surfactant group (n=28), and an equal volume of air was administered to the control group (n=28). Lung compliance was initially low in both groups; after treatment, values were higher with time in the surfactant group ( F =5.40, p =0.026). The ECMO treatment period was significantly shorter in the surfactant group (mean ±SD: 107±33 hours vs 139±54 hours for the control group; U =232, p =0.023). Tracheal aspirate concentrations of surfactant protein A were low in both groups, and then increased steadily to a higher level in the surfactant group ( F =2.58, p =0.04). The overall incidence of complications after ECMO was decreased in the surfactant group (18% vs 46% for the control group; chi-square value=5.004, p =0.025). Radiographic scores, echocardiographic findings, incidence of intracranial or pulmonary hemorrhage and bronchopulmonary dysplasia, time to extubation, duration of oxygen therapy, and duration of hospitalization did not differ between the two groups. Beractant in this population improved pulmonary mechanics, Increased surfactant protein A content in tracheal aspirate, decreased time on ECMO duration, and reduced disease complications.