colfosceril-palmitate and Respiratory-Distress-Syndrome--Newborn

Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of pulmonary surfactant. Numerous surfactants of either animal extract or synthetic design have been shown to improve outcomes. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested.. To assess the effect of administration of synthetic surfactant containing surfactant protein mimics compared to animal derived surfactant extract on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having RDS.. Standard search methods of the Cochrane Neonatal Review Group were used. The search included MEDLINE (1966 - May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) in all languages. In addition, published abstracts of the Society of Pediatric Research were searched electronically. For abstract books that did not include key words, the search was limited to the relevant sections on pulmonary and neonatology. The bibliography cited in each publication was obtained and searched in order to identify additional relevant articles.. Randomized and quasi-randomized controlled clinical trials were considered for this review. Studies that enrolled preterm infants or low birth weight infants at risk for or having RDS who were treated with either a synthetic surfactant containing surfactant protein mimics or an animal-derived surfactant preparation were included for this review. Studies that either attempted to treat or prevent respiratory distress syndrome were included.. Primary outcome measures, including mortality, chronic lung disease and multiple secondary outcome measures were abstracted by the reviewers. Statistical analysis was performed using Review Manager software. Categorical data was analyzed using relative risk, risk difference, and number needed to treat. 95% confidence intervals reported. A fixed effects model was used for the meta-analysis. Heterogeneity was assessed using the I-squared statistic.. Two studies were identified that compared protein containing synthetic surfactants to animal derived surfactant preparations. In a meta-analysis of these two studies, infants who received protein containing synthetic surfactant compared to animal derived surfactant extract did not demonstrate significantly different risks of prespecified primary outcomes: mortality at 36 weeks [typical RR 0.81 (95% CI 0.64, 1.03)], chronic lung disease at 36 weeks [typical RR 0.99 (95% CI 0.84, 1.18)], or the combined outcome of mortality or chronic lung disease at 36 weeks [typical RR 0.96 (95% CI 0.82, 1.12)]. There were also no differences in any of the secondary outcomes regarding complications of prematurity between the two surfactant groups with the exception of necrotizing enterocolitis. A decrease in the risk of necrotizing enterocolitis was noted in infants who received protein containing synthetic surfactants compared to animal derived surfactant extract [typical RR 0.60 (95% CI 0.42, 0.86)]. However, this was a secondary outcome in both of the primary studies and there was moderate heterogeneity between the studies.. In two trials of protein containing synthetic surfactants compared to animal derived surfactant extract, no statistically different clinical differences in death and chronic lung disease were noted. Further well designed studies of adequate size and power will be needed to confirm and refine these findings.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Biological Products; Drug Combinations; Fatty Alcohols; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Phosphatidylglycerols; Phospholipids; Proteins; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn

To review exogenous surfactant use in the treatment of respiratory distress syndrome (RDS) in premature neonates.. A MEDLINE search and extensive review of journals was conducted to identify the information for this review from 1983 to 1995 using the following key words: prematurity, surfactant, clinical trials, beractant, Survanta, colfosceril, Exosurf, and neonatal respiratory distress syndrome.. All articles were considered for possible inclusion in the review. Emphasis was placed on controlled studies involving beractant and colfosceril palmitate.. Results of published clinical trials using beractant or colfosceril palmitate in premature infants at risk for RDS have shown improvement in the need for supplemental oxygen and ventilatory support over the course of RDS and a reduction in pneumothorax. However, there was little impact on the incidence of intraventricular hemorrhage. Clinical trials studying the treatment of established RDS have also shown similar improvements. In a comparison of prophylactic versus late treatment, no distinct advantage of preventive treatment was found, except among infants less than 26-28 weeks gestation. Single versus multiple-dose studies have shown no specific advantage of more than two doses of colfosceril palmitate. A comparison trial of beractant and colfosceril palmitate has shown no difference in outcome. Long-term follow-up studies have been encouraging among infants being treated with exogenous surfactant.. The use of beractant and colfosceril palmitate in premature infants has clearly decreased morbidity and mortality associated with RDS. Only one trial has compared the efficacy of beractant with that of colfosceril in the treatment of RDS. There does not appear to be a distinct advantage of one product over another. Early treatment of infants at highest risk for RDS, those less than 26-28 weeks gestation, seems to be beneficial over waiting for RDS to progress in severity. Further research needs to be performed to determine the optimal dosing and timing of these agents, as well as comparative trials studying efficacy. Criteria for use of these products need to be further defined to decrease the incidence of unnecessary treatment.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Biological Products; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Phosphorylcholine; Polyethylene Glycols; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn

Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved through the addition of peptides, such as sinapultide, that mimic the action of human 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 surfactant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syndrome (RDS) and RDS-related death.. We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of < or =32 weeks gestational age, to receive colfosceril palmitate (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 dysplasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Primary outcomes, air leaks, and causes of death were assigned by an independent, masked, adjudication committee with prespecified definitions. The study was monitored by an independent data safety monitoring board.. Lucinactant reduced significantly the incidence 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 difference 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 common 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).. Lucinactant is a more effective surfactant preparation than colfosceril palmitate for the prevention of RDS. In addition, lucinactant reduces the incidence 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.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Biological Products; Bronchopulmonary Dysplasia; Drug Combinations; Fatty Alcohols; Female; Humans; Incidence; Infant Mortality; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Phosphatidylglycerols; Proteins; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Survival Analysis

To review exogenous surfactant use in the treatment of respiratory distress syndrome (RDS) in premature neonates.. A MEDLINE search and extensive review of journals was conducted to identify the information for this review from 1983 to 1995 using the following key words: prematurity, surfactant, clinical trials, beractant, Survanta, colfosceril, Exosurf, and neonatal respiratory distress syndrome.. All articles were considered for possible inclusion in the review. Emphasis was placed on controlled studies involving beractant and colfosceril palmitate.. Results of published clinical trials using beractant or colfosceril palmitate in premature infants at risk for RDS have shown improvement in the need for supplemental oxygen and ventilatory support over the course of RDS and a reduction in pneumothorax. However, there was little impact on the incidence of intraventricular hemorrhage. Clinical trials studying the treatment of established RDS have also shown similar improvements. In a comparison of prophylactic versus late treatment, no distinct advantage of preventive treatment was found, except among infants less than 26-28 weeks gestation. Single versus multiple-dose studies have shown no specific advantage of more than two doses of colfosceril palmitate. A comparison trial of beractant and colfosceril palmitate has shown no difference in outcome. Long-term follow-up studies have been encouraging among infants being treated with exogenous surfactant.. The use of beractant and colfosceril palmitate in premature infants has clearly decreased morbidity and mortality associated with RDS. Only one trial has compared the efficacy of beractant with that of colfosceril in the treatment of RDS. There does not appear to be a distinct advantage of one product over another. Early treatment of infants at highest risk for RDS, those less than 26-28 weeks gestation, seems to be beneficial over waiting for RDS to progress in severity. Further research needs to be performed to determine the optimal dosing and timing of these agents, as well as comparative trials studying efficacy. Criteria for use of these products need to be further defined to decrease the incidence of unnecessary treatment.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Biological Products; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Phosphorylcholine; Polyethylene Glycols; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn

The effect of a 50% increment or decrement in the recommended 5 ml/kg dose of a commercially available surfactant (Exosurf Neonatal) on the alveolar-arterial oxygen gradient was investigated in a multicenter, double-blind, placebo-controlled rescue trial conducted at 15 hospitals in the United States. Two doses of three different volumes (2.5, 5.0, and 7.5 ml/kg) were compared with two 5.0 ml/kg doses of air in 281 infants weighing > or = 1250 gm who had respiratory distress syndrome requiring mechanical ventilation and an arterial/alveolar oxygen ratio < 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to all infants who still required mechanical ventilation. Infants were stratified at entry by gender and the magnitude of the arterial/alveolar oxygen ratio. The air placebo arm of the study was terminated early when reductions in mortality rates were proved in another rescue trial of this surfactant in infants with the same birth weights. For the first 48 hours, administration of a 2.5 ml/kg dose of surfactant provided less improvement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5 ml/kg, which were equivalent. Similar results were observed in mean airway pressure (p < 0.05). There were no significant differences among the three dosage groups in mortality rate, air leak, bronchopulmonary dysplasia, and other complications of prematurity. There were no pulmonary hemorrhages in any group. Reflux of surfactant occurred more frequently in the 5.0 and 7.5 ml/kg groups. These results indicate that more sustained improvements in oxygenation are provided, with equal safety, by the standard two 5.0 ml/kg rescue doses of this surfactant than by the 2.5 ml/kg dose. No further benefit is gained from two larger doses given 12 hours apart.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Birth Weight; Blood Pressure; Double-Blind Method; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Oxygen; Oxygen Inhalation Therapy; Pulmonary Gas Exchange; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties.. A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten®.. The sSP-C PS and Surfacten® were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten®, and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten® revealed similar properties.. In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten®. Further study is required to evaluate the in vivo efficacy.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Adsorption; Amino Acid Sequence; Animals; C-Peptide; Cattle; Humans; Infant, Newborn; Pulmonary Surfactant-Associated Protein C; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface Properties; Surface Tension; Surface-Active Agents

Topics: 1,2-Dipalmitoylphosphatidylcholine; Biological Products; Bronchopulmonary Dysplasia; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Phosphatidylglycerols; Phospholipids; Proteins; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn

Comprehensive clinical data provide strong evidence of the efficacy of the synthetic lung surfactant colfosceril palmitate (Exosurf Neonatal) administered as prophylaxis or rescue therapy in infants with respiratory distress syndrome (RDS). The use of rescue therapy with colfosceril palmitate is further supported by cost-effectiveness analyses which report a 9 to 48% reduction in the cost per survivor compared with placebo or historical controls, despite divergent study methodology and location. Importantly, the savings were evident in both larger (> or = 1250g) and smaller (700 to 1350g) infants. All studies considered costs or charges accrued during initial hospitalisation through to 1 year; measurement of long term resource use data and all resulting costs are required for a more complete pharmacoeconomic evaluation. The optimal timing of surfactant administration is likely to be an important economic issue given that efficacy data from a large international trial support earlier administration of colfosceril palmitate versus delayed therapy in high risk patients. Further economic benefits may be realised by the sequential use of antenatal corticosteroids and surfactant therapy, although this has yet to be prospectively investigated. In conclusion, clinical and pharmacoeconomic data strongly support the use of rescue therapy with colfosceril palmitate. Additionally, recent clinical data indicating that even better results may be achieved with earlier administration and/or combined use with antenatal corticosteroids should be assessed from an economic standpoint to determine the optimal prescribing strategy for this agent.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Cost-Benefit Analysis; Economics, Pharmaceutical; Follow-Up Studies; Humans; Infant; Infant, Newborn; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn