Showing papers on "Lucinactant published in 2005"
TL;DR: Lucinactant and poractant alfa were similar in terms of efficacy and safety when used for the prevention and treatment of RDS among preterm infants, with the lower boundary of the 95% CI for the difference being greater than the prespecified noninferiority margin.
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, KL4 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. The ability to enhance the performance of a synthetic surfactant with the addition of a peptide that mimics the action of SP-B, such as sinapultide, brings potential advantages to exogenous surfactant therapy.
190 citations
TL;DR: It is concluded 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.
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.
176 citations
TL;DR: Clinical studies have shown that treatment with these novel surfactant preparations can ameliorate RDS and improve clinical outcome and there is concern regarding the hypothetical risk of transmission of viral or unconventional infectious agents from an animal source.
Abstract: Surfactant preparations have been proven to improve clinical outcome of infants at risk for or having respiratory distress syndrome (RDS) In clinical trials, ani mal-derived surfactant preparations reduce the risk of pneumothorax and mortality when compared to non-protein-containing synthetic surfactant preparations In part, this is thought to be due to the presence of surfactant proteins in animal-derived surfactant preparations Four native surfactant proteins have been identified The hydrophobic surfactant proteins B (SP-B) and C (SP-C) are tightly bound to phospholipids These proteins have important roles in maintaining the surface tension-lowering properties of pulmonary surfactant Surfactant protein A (SP-A) and D (SP-D) are extremely hydrophilic and are not retained in the preparation of any commercial animal-derived surfactant products These proteins are thought to have a role in recycling surfactant and improving host defense There is concern that animal-derived products may have some batch-to-batch variation regarding the levels of native pulmonary surfactant proteins In addition, there is concern regarding the hypothetical risk of transmission of viral or unconventional infectious agents from an animal source New surfactant preparations, composed of synthetic phospholipids and essential hydrophobic surfactant protein analogs, have been developed These surfactant protein analogs have been produced by peptide synthesis and recombinant technology to provide a new class of synthetic surfactants that may be a suitable alternative to animal-derived surfactants Preliminary clinical studies have shown that treatment with these novel surfactant preparations can ameliorate RDS and improve clinical outcome Clinicians will need to further understand any differences in clinical effects between available products
39 citations
TL;DR: Randomised clinical trials suggest that this compound is a safe and effective treatment for respiratory distress syndrome in preterm infants and it is also being actively investigated for other indications, including meconium aspiration syndrome, treatment of bronchopulmonary dysplasia in neonates and asthma.
Abstract: Lucinactant (Surfaxin®, Discovery Laboratories) is a synthetic surfactant, which contains the novel peptide, sinapultide, a surfactant-associated proteinB mimic. Randomised clinical trials suggest that this compound is a safe and effective treatment for respiratory distress syndrome in preterm infants. It is also being actively investigated for other indications, including meconium aspiration syndrome, treatment of bronchopulmonary dysplasia in neonates, acute respiratory distress syndrome and asthma. A novel aerosol formulation administered with nasal continuous positive airway pressure is also under development for treatment of respiratory insufficiency in neonates. Its non-animal origin may make it an attractive alternative to present animal-derived surfactants by eliminating the risks of infection and immunogenicity related to the latter.
18 citations
TL;DR: In the pivotal randomized, double-blind, prophylaxis trial in premature infants, the incidence of RDS at 24 hours after birth was significantly lower in lucinactant recipients than in recipients of colfosceril palmitate, a synthetic non-protein-containing surfactant.
Abstract: Lucinactant, formerly known as KL(4) surfactant, is a novel synthetic lung surfactant containing phospholipids and an engineered peptide, sinapultide, which is designed to mimic the actions of human surfactant protein B. It has been developed for use in the prevention or treatment of respiratory distress syndrome (RDS), a common problem in premature infants, which results from a deficiency or degradation of pulmonary surfactant. Lucinactant is administered intratracheally soon after birth as a replacement surfactant. In the pivotal randomized, double-blind, prophylaxis trial in premature infants, the incidence of RDS at 24 hours after birth was significantly lower in lucinactant recipients than in recipients of colfosceril palmitate, a synthetic non-protein-containing surfactant. RDS-related mortality at 14 days was significantly lower in lucinactant recipients than in recipients of colfosceril palmitate or beractant, a bovine-derived surfactant. In another randomized, double-blind, prophylaxis trial in premature infants, the rate of survival without bronchopulmonary dysplasia at 28 days of age in lucinactant recipients was not inferior to that in recipients of poractant alfa, a porcine-derived surfactant. Lucinactant was generally well tolerated. Adverse events were transient and related to the administration procedure. There were no differences in the incidences of complications of prematurity between lucinactant and the other surfactants.
6 citations
TL;DR: The synthetic surfactant lucinactant may reduce total initial NICU hospital costs in surviving infants who receive surfactan therapy when compared to pooled animal-derived surfactants.
Abstract: 140 Preventing Respiratory Distress Syndrome: A Comparative Pharmacoeconomic Analysis of Lucinactant (Surfaxin) Versus Pooled Animal-Derived Surfactants
3 citations
TL;DR: The early survival advantage observed through 36-wks PMA in premature infants treated with Surfaxin compared with animal-derived surfactants as well as a synthetic, non-protein-containing surfactant was maintained through 1-year corrected age.
Abstract: 134 Long-Term Outcomes of Lucinactant (Surfaxin) Vs. Animal-Derived and Synthetic, Non–Protein-Containing Synthetic Surfactants in Very Preterm Infants
3 citations
TL;DR: Among surviving pre-term infants diagnosed with NEC who received surfactant therapy, the synthetic protein-containing surfactan lucinactant reduced total initial NICU hospital costs when compared to pooled animal-derived surfactants.
Abstract: 406 Infants with Necrotizing Enterocolitis: Pharmacoeconomic Analysis of Lucinactant (Surfaxin) Versus Pooled Animal-Derived Surfactants in Preventing RDS
1 citations