Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs.

BACKGROUND: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans. METHODS: Newborn pigs (n = 18) were exposed to 2-h hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15 or 15-20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30 min with a 60 min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF. RESULTS: Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI. CONCLUSION: The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.

In vitro surfactant and perfluorocarbon aerosol deposition in a neonatal physical model of the upper conducting airways.

OBJECTIVE: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. METHODS: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4-7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. RESULTS: The nebulization system produced relatively large amounts of aerosol ranging between 0.3±0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0±0.1 ml/min for distilled water (H2Od) at 6 bar, with MMADs between 2.61±0.1 µm for PFD at 7 bar and 10.18±0.4 µm for FC-75 at 6 bar. The deposition study showed that for surfactant and H2Od aerosols, the highest percentage of the aerosolized mass (∼65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH2O only increased total airway pressure by 1.59 cmH2O at the highest driving pressure (7 bar). CONCLUSION: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support.

Dobutamine in paediatric population: a systematic review in juvenile animal models.

OBJECTIVE: Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/paediatric population. METHODS: Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included. RESULTS: Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions. CONCLUSION: There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.

The role of coagulase-negative staphylococci in early onset sepsis in a large European cohort of very low birth weight infants.

BACKGROUND: Early Onset Sepsis (EOS) is associated with increased major morbidity and mortality rates among very low birth weight (VLBW) infants. The epidemiology is changing in response to evolving medical practice. The objective of the study was to evaluate EOS epidemiology, risk factors, mortality and major morbidity rates among VLBW infants within a European cohort. METHODS: Data from VLBW infants born from 2006 through 2009 was collected by neonatal units participating in the EuroNeoNet initiative. Univariate and multivariate analyses were performed to assess the independent association of EOS with VLBW infant's perinatal characteristics, morbidity and mortality rates. RESULTS: The cohort included 14,719 infants, 391 developed EOS (2.7%). The most common pathogen responsible for EOS was Gram-positive bacteria (53.9%). Coagulase-negative staphylococci (CoNS) were isolated in 22.5% of episodes. Antenatal steroids exposure, single gestation, very low gestational age and birth weight, low 5 minute Apgar score and delivery room resuscitation were independently associated with EOS. EOS was also associated with a longer hospital stay, increased risk of mortality [adjusted odd ratio (aOR): 2.4; 95% Confidence Interval (CI): 1.9-3.1], respiratory distress syndrome (OR: 1.4; 95% CI: 1.1-1.9), severe intraventricular haemorrhage (aOR: 2.1; 95%CI: 1.6-2.8) and severe retinopathy of prematurity (aOR: 5; 95% CI: 1.9-13.3). Morbidity and mortality rates of infants with EOS caused by CoNS were similar to those of infants with EOS caused by other pathogens. CONCLUSIONS: VLBW infants with EOS are at an increased risk of mortality and major morbidities. CoNS was a significant cause of sepsis, infants with CoNS were at a similarly high risk of complication of prematurity and mortality as those with EOS caused by other organisms.

Aerosolized perfluorocarbon improves gas exchange and pulmonary mechanics in preterm lambs with severe respiratory distress syndrome.

BACKGROUND: Aerosolized perfluorocarbon (PFC) has been proposed as an alternative method of PFC administration; however, the efficacy of aerosolized PFC in a preterm animal model has not yet been demonstrated. METHODS: Twelve preterm lambs were randomized to two groups: a perfluorodecalin (PFD) aerosol group (n = 6) receiving 10 ml/kg/h of PFD delivered by an intratracheal inhalation catheter followed by 4 h of mechanical ventilation (MV) or the control group, in which animals (n = 6) were managed for 6 h with MV. Gas exchange, pulmonary mechanics, cardiovascular parameters, and cerebral blood flow (CBF) were measured. RESULTS: Both groups developed hypoxia, hypercarbia, and acidosis at baseline. Aerosolized PFD improved oxygenation (P < 0.0001) and pulmonary mechanics (P < 0.0001) and changed carbon dioxide values to normal physiological levels, unlike the treatment given to the controls (P < 0.0003). The time course of mean arterial blood pressure and CBF were significantly affected by PFD aerosolization, especially during the first hour of life. CBF gradually decreased during the first hour in the PFD aerosol group and remained stable until the end of the follow-up, whereas CBF remained higher in the control group (P < 0.0028). CONCLUSION: Aerosolized PFD improves pulmonary function in preterm lambs and should be further investigated as an alternative mode of PFC administration.

Surfactant and perfluorocarbon aerosolization during different mechanical ventilation strategies by means of inhalation catheters: an in vitro study.

BACKGROUND: Aerosol delivery of surfactant and perfluorocarbon (PFC) is a desirable therapeutic approach for the treatment of various lung diseases in patients undergoing mechanical ventilation. However, the behavior of these substances during aerosolization differs significantly from that of aqueous solutions. In particular, the high vapor pressure of many PFCs tends to result in greater evaporation during mechanical ventilation. METHODS: Three PFCs and surfactant were aerosolized during mechanical ventilation by means of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, and IC-1.4), with their aerosol generating tip placed at the distal end of the endotracheal tube (i.d. 4 mm). The influence of four different ventilation strategies on aerosol production rate and PFC and surfactant recovery was studied. The changes in intrapulmonary pressure produced by the air jets of each IC were measured. RESULTS: With IC-1.23 and IC-1.1, the highest rates of aerosol production were achieved using FC75 (2.27±0.18 and 0.76±0.01, respectively) followed by PFOB (1.74±0.06 and 0.56±0.04), PFD (0.82±0.01 and 0.21±0.01), and surfactant (0.42±0.05 and 0.092±0.01). With IC-1.4 modest aerosol production was obtained irrespective of the aerosolized compound. Mechanical ventilation influenced aerosol recovery, with the trend being toward recovering higher percentages of the compounds with lower peak inspiratory pressure (PIP) and lower respiratory rate (RR) settings. The highest percentages of the initial volume were recovered with IC-1.23 (between 65.43%±4.2 FC75 and 90.21%±4.71 surfactant) followed by IC-1.1 (between 46.48%±4.46 FC75 and 73.19%±2.82 PFOB) and IC-1.4 (between 4.65%±4.36 FC75 and 63.24%±9.71 surfactant). Each of three of the ICs were found to increase the intrapulmonary pressure by about 2-3 cmH2O during mechanical ventilation. CONCLUSIONS: Despite of mechanical ventilation, IC-1.23 and IC-1.1 were able to deliver significant amounts of surfactant and perfluorocarbon to the lung model. Changes in PIP and RR directly influence the percentage of surfactant and perfluorocarbon recovered.

Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic-Ischemic Fetal Lambs during Postnatal Life.

The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

Pediatric clinical trials in Latin America and Guyana: present views of local practitioners and ways to embrace the future.

BACKGROUND: Global pediatric research has recently received increased attention by health professionals, and research and government institutions. Since the approval of the FDA Pediatric Exclusivity Provision and the EU Paediatric Regulation, pharmaceutical companies have begun to look to developing/transitional countries for international pediatric research collaboration as a way of facilitating the recruitment of patients to clinical trials. Among countries identified as being 'developing/transitional' some were in the North, Central, and South American regions. OBJECTIVE AND METHODS: The aim of this study was to ascertain views from local practitioners on awareness and understanding of pediatric clinical research and to clarify resources and training required by pediatricians engaging in such research in the North, Central, and South American regions. A brief survey was disseminated via Sociedad Iberoamericana de Neonatología (SIBEN) and several other randomly selected pediatric institutions. This survey provided information for a Paediatric Global Research meeting at WorldPharma 2010 (Copenhagen, Denmark). RESULTS: Pediatricians (n = 55) from seven countries in Latin America and Guyana replied to the survey. They appeared to be enthusiastic about embracing the opportunity to participate in meaningful research to improve treatment of children worldwide. However, some challenges remain to be addressed around good clinical practice in the conduct of trials, education, and training of professionals, and the availability and use of resources. CONCLUSION: The survey indicated a considerable depth of interest in the improvement of the pediatric clinical research environment in Latin America. There is some momentum toward the development of a Latin American network for the facilitation and supervision of pediatric clinical research.

Surfactant and perfluorocarbon aerosolization by means of inhalation catheters for the treatment of respiratory distress syndrome: an in vitro study.

BACKGROUND: The aerosolization of perfluorocarbons or surfactant has emerged as a feasible alternative to instillation, for the treatment of experimental respiratory distress syndrome. However, the biophysical properties that make these compounds useful in such therapies, significantly affect the performance of nebulizers. Therefore, in vitro studies are required to assess the suitability of new aerosolization technologies for use with these compounds. METHODS: The aim of the present in vitro study was to investigate the influence of the biophysical properties of perfluorocarbons (PFD, FC75, and PFOB) and a natural porcine surfactant, Curosurf®; on aerosolization and to assess the suitability of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, IC-1.4) coupled to a jet nebulizer, for aerosol delivery of these compounds. RESULTS: With IC-1.23 significantly higher aerosol production rates were achieved (p < 0.0001), ranging between 6.05 ± 0.17 mL/min (FC75) and 1.94 ± 0.09 mL/min (Curosurf®), and lower percentage losses of the compound (5-21%), compared to IC-1.1 and IC-1.4 catheters. The lowest aerosolization rates were produced with IC-1.4 ranging from 0.58 ± 0.02 mL/min (FC75) to 0.14 ± 0.01 mL/min (Curosurf®), and this catheter also resulted in the highest percentage losses (25-60%). The mass median aerodynamic diameter (MMAD) ranged between 0.77 µm (PFD) and 8.29 µm (Curosurf®) with IC-1.1, whereas higher MMAD values, of between 4.84 µm (FC75) and 13.42 µm (PFOB), were observed with IC-1.23. Regardless of the catheter used during aerosolization, the perfluorocarbon with the highest kinematic viscosity showed the lowest aerosolization and emission rates and vice versa, which reveals the substantial contribution of this parameter that should accordingly be considered in the design of perfluorocarbon aerosol drug delivery systems. CONCLUSIONS: Jet aerosolization of perfluorocarbons or surfactant with the intratracheal inhalation catheters seems to be a suitable method for treating experimental respiratory distress syndrome, because it delivers relatively high doses of perfluorocarbons and surfactant to the lungs in a respirable size droplets.

Educational strategy to reduce medication errors in a neonatal intensive care unit.

OBJECTIVE: We aimed to evaluate the effect of a comprehensive preventive educational strategy on the number and type of drug errors in the prescription process in a regional neonatal intensive care unit (NICU). DESIGN: Medication errors during prescription were recorded in a 41 bed, level III regional neonatal unit by a pharmacist. Data were retrieved from handwritten doctor's orders and introduced at bedsite into an e-database. Each prescription, not related to enteral and parenteral nutrition and blood products, was evaluated for dosage, units, route and dosing interval. The study was developed in three phases: pilot phase to know the baseline drug error rate and estimate sample size; pre-intervention (4182 drug orders reviewed); and post-intervention seven months after a comprehensive preventive educational intervention consisting sessions about drug errors and study's aims was implemented. RESULTS: After the preventive educational intervention was implemented, the prescription error rate and the percentage of registers with one or more incident decreased significantly from 20.7 to 3% (p < 0.001) and from 19.2 to 2.9% (p < 0.001), respectively. Simultaneously, an improvement in correct identification of the prescribing physician was registered (from 1.3 to 78.2%). The rest of items analysed were similar in both periods. CONCLUSION: The implementation of a structured preventive educational intervention for health professionals in a regional NICU reduced the medication error rate, possibly by the dissemination of a patient safety culture.

European online postgraduate educational programme in neonatology-the way forward?

The provision of specialist postgraduate training is increasingly challenging for the acute medical specialties. There are often small numbers of trainees and tutors in any one centre, and service commitments may limit attendance at educational activities. Online learning can provide high-quality education to trainees from large geographical areas. We report the outcomes of an experimental educational project which provided an online postgraduate programme in neonatology. Ninety trainees from 14 countries, primarily European, participated. Six educational modules in neonatal topics were delivered over a 1-year period, within a "Virtual Learning Environment". Trainees were divided into multi-national groups; two online tutors supported each group. Analysis of online activity demonstrated that active participation was high initially (100%) but gradually declined to 46% in the final module; tutor participation followed a similar pattern. Eighty-six trainees were contactable at the end of the programme, and 67 (78%) completed an evaluation questionnaire. Of these, 92% reported that participation had "added value" to their training, attributable to the high-quality curriculum, the educational resources, collaborative networking and the sharing of best practice. Eleven (79%) tutors completed the questionnaire, with all reporting that participation was of educational value. The main limiting factor for trainees and tutors was insufficient time. This project confirms that multi-national online education in neonatology is feasible and transferable, but for this approach to be viable formal accreditation and protected time for both trainees and tutors are required.

Medication errors in a neonatal intensive care unit. Influence of observation on the error rate.

AIM: To study if medication error rate decreased as a consequence of a simple observation process of registering its occurrence. METHODS: Prescription and transcription processes were prospectively registered along two different period of time in a level III regional Neonatal Intensive Care Unit: a pilot phase, aimed to know the baseline drug error rate and a phase I, a pre-intervention phase, both part of a study designed to determinate the effect of a preventive strategy in drug error rate. Random drug prescriptions by physicians and their transcriptions by nurses were reviewed and registered by a hospital pharmacist. A drug error episode was registered if dosage, units, route and administration interval were incorrect, illegible or not indicated. RESULTS: A significant reduction in the prescription error rate from 32.8% in the pilot phase to 19.2% in the pre-intervention study phase was observed (p< 0.001). Rates of incorrect dosing (13.6% vs. 5%) and lack of dose specification in the medical prescriptions (3.3% vs. 0.5%) dropped significantly but transcription errors did not. CONCLUSION: The presence of a person reviewing and registering the drug records apparently had by itself a substantial positive effect on the overall drug error rate. This phenomenon known as the Hawthorne effect should be taken in consideration when evaluating the efficacy of any preventive intervention aimed at improving patient safety.

European consensus guidelines on the management of neonatal respiratory distress syndrome.

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the recommendations of a European panel of expert neonatologists who developed consensus guidelines after critical examination of the most up-to-date evidence in 2007. Strong evidence exists for the role of antenatal steroids in RDS prevention, but it is not clear if repeated courses are safe. Many practices involved in preterm neonatal stabilization at birth are not evidence based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in management of RDS but the best preparation, optimal dose and timing of administration at different gestations is not always clear. Respiratory support in the form of mechanical ventilation may also be life saving but can cause lung injury, and protocols should be directed to avoiding mechanical ventilation where possible by using nasal continuous positive airways pressure. For babies with RDS to have the best outcome, it is essential that they have optimal supportive care, including maintenance of a normal body temperature, proper fluid management, good nutritional support, management of the ductus arteriosus and support of the circulation to maintain adequate blood pressure.

Early cell death in the brain of fetal preterm lambs after hypoxic-ischemic injury.

The objective of the present study was to evaluate using premature fetal lambs the effect of cerebral hypoxia-ischemia induced by partial occlusion of the umbilical cord on the type of cell death which occurs in different brain regions and to ascertain some of the neural pathways which may underlie the associated pathologies. Lambs were sacrificed either immediately after a 1 h hypoxic-ischemic insult or 3 h later. Brains were fixed by perfusion and blocks of the different brain territories were processed for light microscopy (hematoxylin-eosin, Nissl staining), electron transmission microscopy and quantification of apoptosis by the TUNEL method. Other fixed brains were dissociated and labeled by nonyl acridine orange to determine mitochondrial integrity. Non-fixed brains were also used for membrane asymmetry studies, in which cell suspensions were analyzed by flow cytometry to quantify apoptosis. In both hypoxic-ischemic groups, necrotic-like neurons were observed mainly in the mesencephalon, pons, deep cerebellar nuclei and basal nuclei, whereas apoptotic cells were extensively found both in white and gray matter and were not limited to regions where necrotic neurons were present. The 3 h post-partial cord occlusion group, but not the 0 h group, showed a generalized alteration of cell membrane asymmetry and mitochondrial integrity as revealed by Annexin V/PI flow cytometry and nonyl acridine orange studies, respectively. Our results show that the apoptotic/necrotic patterns of cell death occurring early after hypoxic-ischemic injury are brain-region-specific and have distinct dynamics and suggest that therapeutic strategies aimed at rescuing cells from the effects of hypoxia/ischemia should be aimed at blocking the apoptotic components of brain damage.

Acute and sustained effects of lucinactant versus poractant-alpha on pulmonary gas exchange and mechanics in premature lambs with respiratory distress syndrome.

BACKGROUND: Animal-derived, protein-containing surfactants seem to be superior to protein-free surfactants. Lucinactant, a synthetic surfactant containing a surfactant protein-B peptide analog, has been shown to be effective in animal models and phase II clinical trials. To date, lucinactant has not been compared with an animal-derived surfactant in a premature animal model. OBJECTIVE: The objective was to compare the acute and sustained effects of lucinactant among premature lambs with respiratory distress syndrome (RDS) with the effects of a natural porcine surfactant (poractant-alpha). METHODS: After 5 minutes of mechanical ventilation twin premature lambs were assigned randomly to the lucinactant group (30 mg/mL, 5.8 mL/kg) or the poractant-alpha group (80 mg/mL, 2.2 mL/kg). Heart rate, systemic arterial pressure, arterial pH, blood gas values, and lung mechanics were recorded for 12 hours. RESULTS: Baseline fetal pH values were similar for the 2 groups (pH 7.27). After 5 minutes of mechanical ventilation, severe RDS developed (pH: <7.08; Paco2: >80 mm Hg; Pao2: <40 mm Hg; dynamic compliance: <0.08 mL/cm H2O per kg). After surfactant instillation, similar improvements in gas exchange and lung mechanics were observed for the lucinactant and poractant-alpha groups at 1 hour (pH: 7.3 +/- 0.1 vs 7.4 +/- 0.1; Paco2: 8 +/- 18 mm Hg vs 40 +/- 8 mm Hg; Pao2: 167 +/- 52 mm Hg vs 259 +/- 51 mm Hg; dynamic compliance: 0.3 +/- 0.1 mL/cm H2O per kg vs 0.3 +/- 0.1 mL/cm H2O per kg). The improvements in lung function were sustained, with no differences between groups. Cardiovascular profiles remained stable in both groups. CONCLUSIONS: Among preterm lambs with severe RDS, lucinactant produced improvements in gas exchange and lung mechanics similar to those observed with a porcine-derived surfactant.

A multicenter, randomized, controlled trial of lucinactant versus poractant alfa among very premature infants at high risk for respiratory distress syndrome.

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.