Lucinactant

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Robert Segal - One of the best experts on this subject based on the ideXlab platform.

  • Radiation Mitigating Properties of Intranasally Administered KL4 Surfactant in a Murine Model of Radiation-Induced Lung Damage.
    Radiation research, 2017
    Co-Authors: Melpo Christofidou-solomidou, Ralph A. Pietrofesa, Evguenia Arguiri, Constantinos Koumenis, Robert Segal
    Abstract:

    The threat of exposure to ionizing radiation from a nuclear reactor accident or deliberate terrorist actions is a significant public health concern. The lung is particularly susceptible to radiation-induced injury from external sources or inhalation of radioactive particles from radioactive fallout. Radiation-induced lung disease can manifest with an acute radiation pneumonitis and/or delayed effects leading to pulmonary fibrosis. As prior warning of radiation exposure is unlikely, medical countermeasures (MCMs) to mitigate radiation-induced lung disease that can be given in mass-casualty situations many hours or days postirradiation are needed to prevent both early and late lung damage. In this study, KL4 surfactant (Lucinactant) was evaluated as a radiation mitigator in a well-characterized mouse model of targeted thoracic radiation exposure, for its effect on both early (several weeks) and late (18 weeks) lung damage. Here, 120 mg/kg total phospholipid of KL4 surfactant was administered twice daily intranasally, (enabling intrapulmonary inhalation of drug) to C57BL/6 mice 24 h after a single 13.5 Gy dose of thoracic irradiation (LD50 dose). Both early and chronic phase (2 and 4 weeks and 18 weeks postirradiation, respectively) assessments were performed. Mice were evaluated for evidence of reduced arterial blood oxygenation and early and chronic lung and systemic inflammation, lung fibrosis and oxidative stress. Analysis was done by performing lung function/respiration dynamics and measuring cellular protein content of bronchoalveolar lavage fluid (BALF), and levels of cytokines, 8-iso-prostaglandin F2α, hydroxyproline in lung and plasma, along with evaluating lung histology. The results of this study showed that intranasal delivery of KL4 surfactant was able to preserve lung function as evidenced by adequate arterial oxygen saturation and reduced lung inflammation and oxidative stress; total white count and absolute neutrophil count was decreased in BALF, as were plasma pro-inflammatory cytokine levels and biomarker of oxidative stress. KL4 surfactant is a promising MCM for mitigation of lung tissue damage after targeted, thoracic irradiation and has the potential to be developed as a broad-spectrum, multi-use MCM against chemical, biological, radiological or nuclear threat agents with potential to cause lung injury.

  • A Pharmacoeconomic Analysis of In-Hospital Costs Resulting from Reintubation in Preterm Infants Treated with Lucinactant, Beractant, or Poractant Alfa
    The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2012
    Co-Authors: Carlos Guardia, Fernando R. Moya, Robert Segal, Phillip D. Simmons, Sunil K Sinha, Jay S. Greenspan
    Abstract:

    OBJECTIVES Reintubation and subsequent mechanical ventilation (MV) in preterm infants after surfactant replacement therapy are associated with excess morbidity and mortality and likely increase in-hospital costs. Specific surfactant therapy selection for prevention of respiratory distress syndrome (RDS) in preterm infants receiving conventional MV may impact not only clinical outcomes but also pharmacoeconomic outcomes. METHODS We conducted a pharmacoeconomic analysis of the impact of surfactant selection and reintubation and subsequent MV of preterm infants on health care resource utilization. Rates of reintubation and duration of MV after reintubation were determined from 1546 preterm infants enrolled in two surfactant trials comparing Lucinactant to beractant and poractant alfa. Hospital costs were obtained from a 2010 US database from 1564 preterm infants with RDS, with a direct cost of $2637 per day for MV in the neonatal intensive care unit. Cost of reintubation by study and treatment was estima...

  • A pilot, randomized, controlled clinical trial of Lucinactant, a peptide-containing synthetic surfactant, in infants with acute hypoxemic respiratory failure
    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Car, 2012
    Co-Authors: Neal J. Thomas, Carlos Guardia, Fernando R. Moya, Ira M. Cheifetz, Barry P. Markovitz, Pablo Cruces, Phillip Barton, Robert Segal, Phillip D. Simmons, Adrienne G. Randolph
    Abstract:

    Background: Inhibition of surfactant function and abnormal surfactant synthesis lead to surfactant dysfunction in children with acute hypoxemic respiratory failure.] Objective: We evaluated whether intratracheal Lucinactant, a synthetic, peptide-containing surfactant, was safe and welltolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes. Methods and Main Results: Infants ≤2 yrs of age with acute hypoxemic respiratory failure were enrolled in a phase II, doubleblind, multinational, placebo-controlled randomized trial across 36 pediatric intensive care units. Infants requiring mechanical ventilation with persistent hypoxemia meeting acute lung injury criteria were randomized to receive intratracheal Lucinactant (175 mg/kg) or air placebo. One retreatment was allowed 12–24 hrs after initial dosing if hypoxemia persisted. Peri-dosing tolerability of intratracheal Lucinactant and adverse experiences were assessed. Mechanical ventilation duration was analyzed using analysis of variance. The Cochran–Mantel–Haenszel test was used for categorical variables. We enrolled 165 infants (84 Lucinactant; 81 placebo) with acute hypoxemic respiratory failure. There were no significant differences in baseline subject characteristics, with the exception of a lower positive-end expiratory pressure and higher tidal volume in placebo subjects. The prevalence of transient peridosing bradycardia and desaturation was significantly higher in the Lucinactant treatment group. There were no statistical differences between groups for other adverse events or mortality. Oxygenation improved in infants randomized to receive Lucinactant as indicated by fewer second treatments (67% Lucinactant vs. 81% placebo, p = .02) and a trend in improvement in partial pressure of oxygen in arterial blood to fraction of inspired oxygen from eligibility to 48 hrs after dose (p = .06). There was a nonsignificant reduction in duration of mechanical ventilation with Lucinactant (geometric least square means: 4.0 days Lucinactant vs. 4.5 days placebo; p = .254). In a subset of infants (n = 22), the duration of mechanical ventilation in children with acute lung injury (partial pressure of oxygen in arterial blood to fraction of inspired oxygen >200) was significantly shorter with Lucinactant (least square means: 2.4 days Lucinactant vs. 4.3 days placebo; p = .006). Conclusions: In mechanically ventilated infants with acute hypoxemic respiratory failure, treatment with intratracheal Lucinactant appeared to be generally safe. An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that Lucinactant might improve lung function in infants with acute hypoxemic respiratory failure. (Pediatr Crit Care Med 2012; 13:00–00)

  • Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy
    Journal of Neonatal-Perinatal Medicine, 2011
    Co-Authors: Carlos Guardia, Fernando R. Moya, Phillip D. Simmons, Janusz Gadzinowski, Sunil K Sinha, Steven M. Donn, Robert Segal
    Abstract:

    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.

  • Pulmonary Distribution of Lucinactant and Poractant Alfa and Their Peridosing Hemodynamic Effects in a Preterm Lamb Model of Respiratory Distress Syndrome
    Pediatric Research, 2010
    Co-Authors: Michael H. Terry, Timothy J. Gregory, Jan Mazela, Robert Segal, T. Allen Merritt, Benjamin Harding, Hobe Schroeder, Jeanette Merrill-henry, Gordon G Power, Arlin B. Blood
    Abstract:

    Tracheal instillation of surfactant to premature newborns improves their survivability but may transiently obstruct airways resulting in undesirable acute effects on cerebral blood flow (CBF) and oxygenation. The acute peridosing hemodynamic effects of surfactant administration may be avoided by minimizing the volume of surfactant administered, but smaller surfactant volumes may also result in less even distribution of surfactant throughout the lung. These experiments were undertaken to compare responses to two surfactants with different dose volumes (porcine-derived poractant alfa, 2.5 mL/kg vs peptide-based synthetic Lucinactant, 5.8 mL/kg) given to newly delivered lambs at 85% gestation. Both surfactants resulted in similar improvements in blood gas values, a doubling of dynamic compliance, increases in brain tissue oxygen tension, and stable blood pressure with no significant change in CBF. Distribution of surfactant throughout the lungs was more uniform with Lucinactant than poractant alfa when assessed by labeled microspheres. We conclude that improvements in lung mechanics, gas exchange, and changes in CBF are comparable for a porcine-derived and peptide-containing synthetic surfactant, despite instilled volumes differing by 2-fold. Intrapulmonary distribution of surfactant is more uniform after a larger volume is instilled.

Thomas H Shaffer - One of the best experts on this subject based on the ideXlab platform.

  • doi:10.1155/2010/394578 Review Article Cultured Human Airway Epithelial Cells (Calu-3): A Model of Human Respiratory Function, Structure, and Inflammatory Responses
    2013
    Co-Authors: Yan Zhu, Aaron Chidekel, Thomas H Shaffer
    Abstract:

    Copyright © 2010 Yan Zhu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compare

  • Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS
    Pediatric Research, 2012
    Co-Authors: Marla R. Wolfson, Timothy J. Gregory, Jan Mazela, Terrence L. Hubert, Thomas H Shaffer
    Abstract:

    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.

  • Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS.
    Pediatric Research, 2012
    Co-Authors: Marla R. Wolfson, Timothy J. Gregory, Jan Mazela, Jichuan Wu, Terrence L. Hubert, Thomas H Shaffer
    Abstract:

    Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS

  • Cultured Human Airway Epithelial Cells (Calu-3): A Model of Human Respiratory Function, Structure, and Inflammatory Responses
    Critical care research and practice, 2010
    Co-Authors: Yan Zhu, Aaron Chidekel, Thomas H Shaffer
    Abstract:

    This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compared with Beractant and control, and perfluorocarbons also protect against hyperoxia-induced airway epithelial cell injury. The Calu-3 cell preparation is a sensitive and efficient preclinical model to study human respiratory processes and diseases related to oxygen- and ventilator-induced lung injury.

  • AEROSURF™ REDUCES LUNG INFLAMMATION, IMPROVES LUNG MECHANICS AND PRESERVES LUNG HISTOMORPHOLOGY IN SPONTANEOUSLY BREATHING CPAP-SUPPORTED PRETERM LAMBS
    Archives of Disease in Childhood, 2008
    Co-Authors: Marla R. Wolfson, Jan Mazela, Daniel J. Malone, T Gregory, Thomas H Shaffer
    Abstract:

    Objective Previous efforts to aerosolize animal-derived surfactants have met with limited efficacy due to inadequate delivery and inactivation. Our objective was to assess the effect of an aerosolized precision-engineered, peptide-containing, synthetic surfactant (Aerosurf™: Lucinactant for inhalation), delivered by a novel aerosol generator on lung mechanics, histomorphology and biomarkers of lung inflammation in spontaneously breathing, very continuous positive airway pressure (CPAP)-supported preterm lambs. Design and Methods Following cesarean section, lambs (n = 14; 126–129 days gestation) were instrumented, delivered, supported with 100% oxygen, CPAP, and caffeine then quasi-randomized to receive CPAP alone or CPAP plus Aerosurf delivered for 90 min using capillary aerosol generator (CAG) technology. Cardiopulmonary parameters were monitored for 4 hrs. Lung IL-6, IL-8, myeloperoxidase (MPO) and histomorphometry were measured. Results At 4 hrs, lambs treated with CPAP plus Aerosurf demonstrated greater PaO2 (p Conclusions Relative to treatment with CPAP alone, Aerosurf delivery by CAG technology improved pulmonary mechanics, lung structure integrity, and reduced lung inflammation in very preterm lambs. These observations support the potential utility of this novel approach to treat preterm infants with respiratory distress syndrome. Supported by Discovery Laboratories, Inc.

Janusz Gadzinowski - One of the best experts on this subject based on the ideXlab platform.

  • Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy
    Journal of Neonatal-Perinatal Medicine, 2011
    Co-Authors: Carlos Guardia, Fernando R. Moya, Phillip D. Simmons, Janusz Gadzinowski, Sunil K Sinha, Steven M. Donn, Robert Segal
    Abstract:

    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.

  • 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, 2007
    Co-Authors: Fernando R. Moya, Jan Mazela, Carlos Guardia, Robert Segal, Janusz Gadzinowski, Sunil K Sinha, Ralph B. D'agostino, Genzhou Liu
    Abstract:

    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.

  • a multicenter randomized controlled trial of Lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome
    Pediatrics, 2006
    Co-Authors: Janusz Gadzinowski, Sunil K Sinha, Thierry Lacazemasmonteil, Adolf Valls I Soler, Thomas E Wiswell, Julia Hajdu, Graham Bernstein, Manuel Sanchezluna, Robert Segal
    Abstract:

    Background. Available therapeutic surfactants are either animal-derived or non-protein-containing synthetic products. Animal-derived surfactants contain variable amounts of surfactant apoproteins, whereas the older-generation synthetic products contain only phospholipids and lack surfactant proteins (SPs). Both decrease morbidity and mortality rates associated with respiratory distress syndrome (RDS) among preterm infants, compared with placebo. However, excess mortality rates have been observed with non-protein-containing synthetic surfactants, compared with the animal-derived products. Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved with the addition of peptides that are functional analogs of SPs. Lucinactant is a new synthetic peptide-containing surfactant that contains sinapultide, a novel, 21-amino acid peptide (leucine and lysine repeating units, KL 4 peptide) designed to mimic human SP-B. It is completely devoid of animal-derived components. Objective. We hypothesized that the outcomes for premature infants treated with Lucinactant and poractant alfa would be similar. Therefore, we compared Lucinactant (Surfaxin; Discovery Laboratories, Doylestown, PA) with porcine-derived, poractant alfa (Curosurf; Chiesi Farmaceutici, Parma, Italy) in a trial to test for noninferiority. Methods. A total of 252 infants born between 24 and 28 weeks of completed gestation, with birth weights between 600 and 1250 g, were assigned randomly in a multicenter, multinational, noninferiority, randomized, controlled study to receive either Lucinactant (n = 124) or poractant alfa (n = 128) within 30 minutes of life. The primary outcome was the incidence of being alive without bronchopulmonary dysplasia (BPD) through 28 days of age. Key secondary outcomes included death at day 28 and 36 weeks postmenstrual age (PMA), air leaks, neuroimaging abnormalities, and other complications related to either prematurity or RDS. An independent, international, data and safety monitoring committee monitored the trial. Results. The treatment difference between Lucinactant and poractant alfa for survival without BPD through 28 days was 4.75% (95% confidence interval [CI]: -7.3% to 16.8%) in favor of Lucinactant, with the lower boundary of the 95% CI for the difference, ie, -7.3%, being greater than the prespecified noninferiority margin of -14.5%. At 28 days, 45 of 119 infants given Lucinactant were alive without BPD (37.8%; 95% CI: 29.1-46.5%), compared with 41 of 124 given poractant alfa (33.1%; 95% CI: 24.8-41.3%); at 36 weeks PMA, the rates were 64.7% and 66.9%, respectively. The corresponding mortality rate through day 28 for the Lucinactant group was lower than that for the poractant alfa group (11.8% [95% CI: 6.0-17.6%] vs 16.1% [95% CI: 9.7-22.6%]), as was the rate at 36 weeks PMA (16% and 18.5%, respectively). There were no differences in major dosing complications. In addition, no significant differences were observed in the incidences of common complications of prematurity, including intraventricular hemorrhage (grades 3 and 4) and cystic periventricular leukomalacia (Lucinactant: 14.3%; poractant alfa: 16.9%). Conclusions. Lucinactant and poractant alfa were similar in terms of efficacy and safety when used for the prevention and treatment of RDS among preterm infants.

  • 134 long term outcomes of Lucinactant surfaxin vs animal derived and synthetic non protein containing synthetic surfactants in very preterm infants
    Pediatric Research, 2005
    Co-Authors: Janusz Gadzinowski, Jan Mazela, Robert Segal, Sunil K Sinha, F Moya, Carlos Guardia
    Abstract:

    134 Long-Term Outcomes of Lucinactant (Surfaxin) Vs. Animal-Derived and Synthetic, Non–Protein-Containing Synthetic Surfactants in Very Preterm Infants

  • a multicenter randomized masked comparison trial of Lucinactant colfosceril palmitate and beractant for the prevention of respiratory distress syndrome among very preterm infants
    Pediatrics, 2005
    Co-Authors: Fernando R. Moya, Robert Segal, Janusz Gadzinowski, Eduardo Bancalari, Vicente Salinas, Benjamin Kopelman, Aldo Bancalari, M K Kornacka, Allen T Merritt, Christopher Schaber
    Abstract:

    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.

Sunil K Sinha - One of the best experts on this subject based on the ideXlab platform.

  • A Pharmacoeconomic Analysis of In-Hospital Costs Resulting from Reintubation in Preterm Infants Treated with Lucinactant, Beractant, or Poractant Alfa
    The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2012
    Co-Authors: Carlos Guardia, Fernando R. Moya, Robert Segal, Phillip D. Simmons, Sunil K Sinha, Jay S. Greenspan
    Abstract:

    OBJECTIVES Reintubation and subsequent mechanical ventilation (MV) in preterm infants after surfactant replacement therapy are associated with excess morbidity and mortality and likely increase in-hospital costs. Specific surfactant therapy selection for prevention of respiratory distress syndrome (RDS) in preterm infants receiving conventional MV may impact not only clinical outcomes but also pharmacoeconomic outcomes. METHODS We conducted a pharmacoeconomic analysis of the impact of surfactant selection and reintubation and subsequent MV of preterm infants on health care resource utilization. Rates of reintubation and duration of MV after reintubation were determined from 1546 preterm infants enrolled in two surfactant trials comparing Lucinactant to beractant and poractant alfa. Hospital costs were obtained from a 2010 US database from 1564 preterm infants with RDS, with a direct cost of $2637 per day for MV in the neonatal intensive care unit. Cost of reintubation by study and treatment was estima...

  • Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy
    Journal of Neonatal-Perinatal Medicine, 2011
    Co-Authors: Carlos Guardia, Fernando R. Moya, Phillip D. Simmons, Janusz Gadzinowski, Sunil K Sinha, Steven M. Donn, Robert Segal
    Abstract:

    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.

  • Lucinactant surfaxin for prevention and treatment of respiratory distress syndrome in newborns
    Pediatric Health, 2009
    Co-Authors: Mithilesh Lal, Sunil K Sinha
    Abstract:

    Respiratory distress syndrome, resulting from the deficiency of endogenous surfactant, remains a leading cause of mortality and morbidity in preterm infants. Exogenous surfactant replacement therapy is one of the most widely researched areas in neonatal medicine and is now accepted as the standard of care for preventing and treating respiratory distress syndrome in these newborns. Exogenous surfactant replacement therapy has evolved in the past three decades, but controversies still exist as to the choice of preparation (i.e., is one better than the others?), dosing and volume of individual preparations, and cost. At present, animal-derived surfactants that contain proteins appear to be the choice of most clinicians; however, they may have the limitation of being derived from animal sources. This has prompted the development of newer synthetic surfactants such as Lucinactant (Surfaxin™, Discovery Laboratories, PA, USA), which contains the protein B mimic synthetic peptide, sinapultide. Although it is not ...

  • Lucinactant (Surfaxin ™ ) for prevention and treatment of respiratory distress syndrome in newborns
    Pediatric Health, 2009
    Co-Authors: Mithilesh K. Lal, Sunil K Sinha
    Abstract:

    Respiratory distress syndrome, resulting from the deficiency of endogenous surfactant, remains a leading cause of mortality and morbidity in preterm infants. Exogenous surfactant replacement therapy is one of the most widely researched areas in neonatal medicine and is now accepted as the standard of care for preventing and treating respiratory distress syndrome in these newborns. Exogenous surfactant replacement therapy has evolved in the past three decades, but controversies still exist as to the choice of preparation (i.e., is one better than the others?), dosing and volume of individual preparations, and cost. At present, animal-derived surfactants that contain proteins appear to be the choice of most clinicians; however, they may have the limitation of being derived from animal sources. This has prompted the development of newer synthetic surfactants such as Lucinactant (Surfaxin™, Discovery Laboratories, PA, USA), which contains the protein B mimic synthetic peptide, sinapultide. Although it is not ...

  • Review: Surfactant respiratory therapy using Surfaxin/sinapultide
    Therapeutic advances in respiratory disease, 2008
    Co-Authors: Mithilesh K. Lal, Sunil K Sinha
    Abstract:

    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.

Fernando R. Moya - One of the best experts on this subject based on the ideXlab platform.

  • A Pharmacoeconomic Analysis of In-Hospital Costs Resulting from Reintubation in Preterm Infants Treated with Lucinactant, Beractant, or Poractant Alfa
    The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2012
    Co-Authors: Carlos Guardia, Fernando R. Moya, Robert Segal, Phillip D. Simmons, Sunil K Sinha, Jay S. Greenspan
    Abstract:

    OBJECTIVES Reintubation and subsequent mechanical ventilation (MV) in preterm infants after surfactant replacement therapy are associated with excess morbidity and mortality and likely increase in-hospital costs. Specific surfactant therapy selection for prevention of respiratory distress syndrome (RDS) in preterm infants receiving conventional MV may impact not only clinical outcomes but also pharmacoeconomic outcomes. METHODS We conducted a pharmacoeconomic analysis of the impact of surfactant selection and reintubation and subsequent MV of preterm infants on health care resource utilization. Rates of reintubation and duration of MV after reintubation were determined from 1546 preterm infants enrolled in two surfactant trials comparing Lucinactant to beractant and poractant alfa. Hospital costs were obtained from a 2010 US database from 1564 preterm infants with RDS, with a direct cost of $2637 per day for MV in the neonatal intensive care unit. Cost of reintubation by study and treatment was estima...

  • A pilot, randomized, controlled clinical trial of Lucinactant, a peptide-containing synthetic surfactant, in infants with acute hypoxemic respiratory failure
    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Car, 2012
    Co-Authors: Neal J. Thomas, Carlos Guardia, Fernando R. Moya, Ira M. Cheifetz, Barry P. Markovitz, Pablo Cruces, Phillip Barton, Robert Segal, Phillip D. Simmons, Adrienne G. Randolph
    Abstract:

    Background: Inhibition of surfactant function and abnormal surfactant synthesis lead to surfactant dysfunction in children with acute hypoxemic respiratory failure.] Objective: We evaluated whether intratracheal Lucinactant, a synthetic, peptide-containing surfactant, was safe and welltolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes. Methods and Main Results: Infants ≤2 yrs of age with acute hypoxemic respiratory failure were enrolled in a phase II, doubleblind, multinational, placebo-controlled randomized trial across 36 pediatric intensive care units. Infants requiring mechanical ventilation with persistent hypoxemia meeting acute lung injury criteria were randomized to receive intratracheal Lucinactant (175 mg/kg) or air placebo. One retreatment was allowed 12–24 hrs after initial dosing if hypoxemia persisted. Peri-dosing tolerability of intratracheal Lucinactant and adverse experiences were assessed. Mechanical ventilation duration was analyzed using analysis of variance. The Cochran–Mantel–Haenszel test was used for categorical variables. We enrolled 165 infants (84 Lucinactant; 81 placebo) with acute hypoxemic respiratory failure. There were no significant differences in baseline subject characteristics, with the exception of a lower positive-end expiratory pressure and higher tidal volume in placebo subjects. The prevalence of transient peridosing bradycardia and desaturation was significantly higher in the Lucinactant treatment group. There were no statistical differences between groups for other adverse events or mortality. Oxygenation improved in infants randomized to receive Lucinactant as indicated by fewer second treatments (67% Lucinactant vs. 81% placebo, p = .02) and a trend in improvement in partial pressure of oxygen in arterial blood to fraction of inspired oxygen from eligibility to 48 hrs after dose (p = .06). There was a nonsignificant reduction in duration of mechanical ventilation with Lucinactant (geometric least square means: 4.0 days Lucinactant vs. 4.5 days placebo; p = .254). In a subset of infants (n = 22), the duration of mechanical ventilation in children with acute lung injury (partial pressure of oxygen in arterial blood to fraction of inspired oxygen >200) was significantly shorter with Lucinactant (least square means: 2.4 days Lucinactant vs. 4.3 days placebo; p = .006). Conclusions: In mechanically ventilated infants with acute hypoxemic respiratory failure, treatment with intratracheal Lucinactant appeared to be generally safe. An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that Lucinactant might improve lung function in infants with acute hypoxemic respiratory failure. (Pediatr Crit Care Med 2012; 13:00–00)

  • Reintubation and risk of morbidity and mortality in preterm infants after surfactant replacement therapy
    Journal of Neonatal-Perinatal Medicine, 2011
    Co-Authors: Carlos Guardia, Fernando R. Moya, Phillip D. Simmons, Janusz Gadzinowski, Sunil K Sinha, Steven M. Donn, Robert Segal
    Abstract:

    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.

  • A pilot randomized, controlled trial of later treatment with a peptide-containing, synthetic surfactant for the prevention of bronchopulmonary dysplasia.
    Pediatrics, 2009
    Co-Authors: Matthew M. Laughon, Carlos Guardia, Fernando R. Moya, Robert Segal, Carl L. Bose, Judy L. Aschner, Steven Mark Donn, Christopher Morabito, James J. Cummings, Genzhou Liu
    Abstract:

    OBJECTIVE Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bronchopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with Lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of > or =0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of Lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%); no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both Lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of Lucinactant, and this warrants further investigation.

  • Surfactant-replacement therapy for respiratory distress syndrome in the preterm and term neonate: congratulations and corrections.
    Pediatrics, 2008
    Co-Authors: Fernando R. Moya, Sunil K Sinha, Ralph B. D'agostino
    Abstract:

    To the Editor. — We would like to express our congratulations to Dr Engle and the American Academy of Pediatrics Committee on Fetus and Newborn on the publication of their clinical report “Surfactant-Replacement Therapy for Respiratory Distress in the Preterm and Term Neonate.” Overall, this document was comprehensive in scope yet sufficiently detailed and referenced to provide practical, evidence-based guidance to the clinician who renders neonatal care. However, the attempt to summarize information from so many studies has led to inaccurate statements that, if left uncorrected, are misleading. The report stated that “[w]hen compared with infants receiving the animal-derived surfactants beractant and poractant alfa, infants receiving Lucinactant were found to have similar rates of mortality and morbidity from respiratory distress syndrome [RDS].”1 One of the studies cited in connection with this statement is the Safety and Effectiveness of Lucinactant Versus Exosurf in a Clinical Trial of RDS in Premature Infants (SELECT) study. …

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