lucinactant

Treat Respir Med 2005; 4 (2): 139-145ADIS DRUG PROFILE 1176-3450/05/0002-0139/$34.95/0

© 2005 Adis Data Information BV. All rights reserved.

LucinactantIn Neonatal Respiratory Distress Syndrome

Marit D. Moen, Caroline M. Perry and Keri Wellington

Adis International Inc., Yardley, Pennsylvania, USA

ContentsAbstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1391. Pharmacological Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1402. Therapeutic Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1413. Tolerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1434. Dosage and Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1445. Lucinactant: Current Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

Features and properties of lucinactant (KL4 surfactant; Surfaxin®)

AbstractIndication

▲ Lucinactant, formerly known as KL4 surfactant, is a novel synthet-ic lung surfactant containing phospholipids and an engineered Focus of this profile Neonatal respiratory distress syndrome

peptide, sinapultide, which is designed to mimic the actions ofMechanism of actionhuman surfactant protein B. It has been developed for use in the

prevention or treatment of respiratory distress syndrome (RDS), aThe exact mechanism is unknown. Lowers surface tension in the lungs, andcommon problem in premature infants, which results from a defi-sinapultide (peptide component) enhances surfactant spreading ability

ciency or degradation of pulmonary surfactant. Lucinactant isadministered intratracheally soon after birth as a replacement Dosage and administration in clinical trials

surfactant.Usual dose 175mg phospholipids/kg birth weight▲ In the pivotal randomized, double-blind, prophylaxis trial in pre-

(5.8 mL/kg; 30 mg/mL)mature infants, the incidence of RDS at 24 hours after birth wassignificantly lower in lucinactant recipients than in recipients of Method of administration Intratracheal dose in conjunction withcolfosceril palmitate, a synthetic non-protein-containing positive pressure inflation

surfactant. RDS-related mortality at 14 days was significantlyTiming of administration Prophylactic treatment: an initial doselower in lucinactant recipients than in recipients of colfosceril

20–30 minutes after birth, maximum ofpalmitate or beractant, a bovine-derived surfactant.two or three additional doses if

▲ In another randomized, double-blind, prophylaxis trial in prema- necessary at 6-hourly intervalsfollowing the initial doseture infants, the rate of survival without bronchopulmonary dyspla-

sia at 28 days of age in lucinactant recipients was not inferior toAdverse eventsthat in recipients of poractant alfa, a porcine-derived surfactant.

▲ Lucinactant was generally well tolerated. Adverse events were Most frequent Transient events during administration,transient and related to the administration procedure. There were including oxygen desaturation, pallor,

dose interruption, endotrachealno differences in the incidences of complications of prematurityobstruction, apnea, bradycardia, and

between lucinactant and the other surfactants. endotracheal tube reflux

140 Moen et al.

Neonatal respiratory distress syndrome (RDS) results from a taining the hydrophilic amino acid lysine (K) and the hydrophobicdeficiency or degradation of pulmonary surfactant in underdevel- amino acid leucine (L) in the sequence KLLLLKLLLLKLL-oped lungs and is common in premature infants.[1] Pulmonary LLKLLLLK. It was designed to mimic the hydrophobic-hydro-surfactant is a mixture of lipids and proteins that forms a layer at philic patterns of endogenous SP-B.[6]

the air-water interface of the alveoli and lowers surface tension to The sinapultide (SP-B equivalent) content of lucinactant isprevent alveolar collapse.[2] Surfactant replacement therapy with 2.67% of the total phospholipids.[5] By contrast, animal-derivedeither animal-derived or synthetic surfactants improves oxygena- surfactants such as beractant and poractant alfa have SP-B con-tion and reduces mortality in premature infants (reviewed by tents of 0.04%[7] and 0.26%.[8] These surfactants are described inSuresh and Soll[3]). These surfactants are currently used as prophy- more detail in section 2.laxis or rescue treatment for premature infants with RDS in The available pharmacological data on lucinactant are from inconjunction with respiratory support.[1] vitro surfactant surface activity studies and from pulmonary func-

Natural bovine or porcine surfactants are obtained by lung tion studies in animals. There is a lack of pharmacokinetic datalavage or extracted from minced lungs.[3] In addition to lipids, regarding distribution of lucinactant in the lungs, absorption intoanimal-derived surfactants contain the hydrophobic surfactant the systemic circulation, and clearance from the lungs. The meta-proteins (SP)-B and SP-C, which are responsible for lowering bolic fate of sinapultide is not known.[9]

surface tension and enhancing the spreading of surfactant. SP-B is Mechanism of Actionconsidered to be the most important of the surfactant proteins

(reviewed by Ainsworth and Milligan[4]). Proteins SP-A and SP-D● The mechanism by which lucinactant lowers surface tension atare lost during the extraction process. Animal-derived surfactants

the alveolar air-water interface has been studied and has providedare clinically effective in the prevention and treatment of RDS, butinformation on the possible mechanism of SP-B function.[6] How-the levels of proteins are low and may vary between batches. Thereever, the structure-function relationships between lipids and pro-is also a theoretical risk of transmitting animal infections.[3]

teins in lung surfactants in general are not fully understood and areSynthetic surfactants available to date have contained

still being investigated.[10]phospholipids but no proteins. Many trials found that synthetic

● The phospholipids, which are known to be responsible for thesurfactants failed to reach the same clinical efficacy assurface tension-lowering ability of lung surfactant,[4] form a mono-animal-derived surfactants.[3] Lucinactant (Surfaxin®)1, formerlylayer at the alveolar air-water interface.[11] Sinapultide is thoughtknown as KL4 surfactant, is a new synthetic surfactant consistingto lie horizontally in the monolayer within the acyl side chains,of phospholipids plus a novel synthetic peptide, sinapultide, de-allowing electrostatic interactions between the hydrophilic resi-signed to mimic human SP-B.dues and the phospholipid polar head groups.[6] This enables the

This profile reviews the use of lucinactant in the prevention andstretches of hydrophobic residues to interact with the acyl side

treatment of neonatal RDS. Lucinactant is also currently beingchains, thereby enhancing the stability of the phospholipid mono-

investigated for potential use in other respiratory conditions, in-layer.[6]

cluding bronchopulmonary dysplasia (BPD), meconium aspiration● Other studies have examined the effects of sinapultide onsyndrome (MAS), and acute respiratory distress syndrome

surfactant function.[12,13] Sinapultide has been shown to speed(ARDS), but discussion of these indications is beyond the scope ofspreading of the phospholipids at an air-water interface, which isthis article.believed to be another function of SP-B and SP-C,[12] and topromote the separation of DPPC-rich and POPG/PA-rich

1. Pharmacological Profilephases.[13]

Lucinactant is a mixture of the phospholipids dipalmitoylphos- Effects on Surface Tensionphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol(POPG) at a ratio of 3 : 1, the fatty acid palmitic acid (PA, 13.5% The pulsating bubble surfactometer has been used to compareby weight), and sinapultide, a synthetic peptide.[5] Sinapultide, the surface tension-lowering abilities of several natural and syn-formerly known as KL4-peptide, is a 21-amino acid peptide con- thetic surfactants including lucinactant.[14-17]

1 The use of trade names is for product identification purposes only and does not imply endorsement.

© 2005 Adis Data Information BV. All rights reserved. Treat Respir Med 2005; 4 (2)

Lucinactant: Adis Drug Profile 141

● In one of the studies, the mean surface tension of the lower lobes and in some scattered small areas elsewhere in thelucinactant bubbles ranged from 2.0–46.1 dynes/cm (minimal to lungs.[14]

maximal bubble radius), which was numerically similar to the ● In the second study, a special adapter was used to allowmean surface tension measurements for natural human surfactant positive end-expiratory pressure to be maintained while(8.7–39.1 dynes/cm).[14] Non-protein-containing surfactant mean lucinactant was administered. The amount of lucinactant distribut-surface tension was measured at 30.5–57.0 dynes/cm.[14]

ed to the right middle lobe and left lower lobe was greater (p <● Another study (which is only available as an abstract) com- 0.03) in monkeys that received lucinactant by this method than in

pared various physical and chemical properties of lucinactant with monkeys that had a break in mechanical ventilation duringseveral other available lung surfactants, including beractant, lucinactant administration.[19] However, the effects on pulmonaryporactant alfa, and colfosceril palmitate.[15] Lucinactant was found function were similar in both groups.[19]

to have the best surface tension-lowering ability; surface tensionvalues were not reported.[15]

2. Therapeutic Efficacy● The surface tension-lowering ability of surfactant can be inhib-

ited by serum components and some reactive oxygen species.[16,17]

The efficacy of lucinactant in the prevention of neonatal RDSThis deterioration of surfactant function can increase the severityhas recently been evaluated in two phase III, randomized, double-of RDS.[16,17] Hypochlorous acid, which is released by activatedblind, active-controlled, prophylaxis, multicenter trials known asneutrophils, decreased the surface tension-lowering ability of nat-SELECT (Safety and Effectiveness of Lucinactant vs Exosurf in aural (rabbit) lung surfactant but not that of lucinactant.[16]

Clinical Trial of RDS in premature infants)[20] and STAR (Surfax-● The ability of lucinactant to lower surface tension was initially

in Therapy Against RDS).[21] Inclusion criteria were a gestationalinhibited by various serum components, but this effect was re-

age of 24–32 weeks,[20] or 24–28 weeks,[21] a birth weight ofversed within several minutes, unlike the reduction in surface

between 600g and 1250g, and successful endotracheal intubationtension-lowering ability of a non-protein-containing phospholipid-

at birth.only mixture, which was not reversed.[17] Lucinactant surface

Lucinactant was administered intratracheally as a single 175tension-lowering ability was inhibited by fibrinogen, but less somg/kg dose between 20 and 30 minutes after birth. All surfactantthan that of beractant.[17] Natural (rabbit) lung surfactant was onlydoses are based on the phospholipid portion of the surfactantminimally inhibited by high levels of fibrinogen.[17]

mixture. Manual or mechanical positive pressure inflation wasused during administration. A maximum of two[21] or three[20]

Effects on Lung Functionadditional identical doses, administered between 6 and 48 hoursafter the initial dose, were allowed if required. Mechanical ventila-● Different animal models of RDS have been used to investigatetion was provided when necessary, according to specific guide-the effect of lucinactant on pulmonary function. In all studies,lines developed for the study.[20,21] Other preterm infant care wasadministration of lucinactant improved oxygenation.[14,18,19] Theprovided according to local standard procedures.mean arterial/alveolar oxygen partial pressure ratio (a/A O2) in

premature rhesus monkeys with RDS that were treated with Lucinactant was compared with colfosceril palmitate (Exosurflucinactant was significantly higher at 9 hours after birth than in Neonatal®), with beractant (Survanta®) as a reference arm, in themonkeys that received the non-protein-containing surfactant SELECT study.[20] Colfosceril palmitate was administered at acolfosceril palmitate (0.38 vs 0.15; p = 0.0001).[14] In a piglet dose of 67.5 mg/kg, and beractant at a dose of 100 mg/kg. Themodel of RDS, lucinactant 100 mg/kg was also significantly (p < STAR study compared lucinactant with poractant alfa (Curosurf®)0.05) superior to colfosceril palmitate and similar to beractant in given at a dose of 175 mg/kg.[21] Survanta® is extracted fromimproving oxygenation.[18] minced bovine lung and Curosurf® from porcine lung mince.[3]

● Two studies performed physical examinations of the lungs of Exosurf Neonatal® is a non-protein-containing syntheticpremature rhesus monkeys after treatment with lucinactant to surfactant that is composed of 84.5% DPPC (also known asinvestigate the distribution of lucinactant in the lungs.[14,19] colfosceril palmitate) and two other agents to aid with spreading.[4]

Lucinactant was administered as an intratracheal bolus dose divid- DPPC is the most abundant phospholipid in all surfactants (endog-ed between the left and right lungs.[14,19] This resulted in general enous and exogenous); the surfactants differ in the levels of DPPCexpansion of the lungs with atelectasis seen at the lower rim of the and inclusion of other components.[4]


142 Moen et al.

The largest trial (SELECT, n = 1294) was event driven and the dose (200 mg/kg) to the remaining patients within 4 hours of birth.results were analyzed using an intent-to-treat analysis,[20] whereas One additional dose of lucinactant was administered if necessary.the STAR trial used a non-inferiority analysis, which excluded If further surfactant treatment was required, lucinactant was dis-nine infants who did not receive lucinactant within 30 minutes of continued and treatment with an approved surfactant was initiated.birth.[21] However, the findings of the trial were confirmed using The primary endpoints for this study were as follows: pulmonaryan intent-to-treat analysis.[21] The required sample size calculated gas exchange (measured by calculation of a/A O2), duration offor the STAR trial was 248 infants per group, although a total of required mechanical ventilation, RDS-related mortality within 28only 252 infants entered the trial because of slow recruitment and days, incidence of BPD at 28 days of age, and a clearing of thethe trial stopping early.[21] diffuse granular density in the lungs, seen in chest radiographs,

which is typical of RDS.The primary endpoints for the SELECT study were the devel-This study excluded infants with congenital anomalies andopment of RDS at 24 hours after birth and RDS-related death

those with severe congenital infection or proven sepsis.[23]within 14 days.[20] RDS was determined by a requirement of ≥0.30FiO2 (fraction of inspired oxygen) and the diagnosis of RDS from

Comparative Trialsa chest radiograph. The primary endpoint of the STAR study (n =252) was survival without BPD at day 28.[21] BPD is a chronic lung

Comparison with Colfosceril Palmitate and Beractant (SELECT)disease that can occur in premature infants after prolonged venti-● The incidence of RDS at 24 hours after birth was significantlylatory support, which is often used to treat RDS. In this study, the

lower in infants who received lucinactant than in recipients ofoccurrence of BPD was defined as requiring mechanical ventila-colfosceril palmitate (39.1% vs 47.2%; OR 0.68, 95% CI 0.52,tion or additional oxygen.[21]

0.89; p = 0.005).[20] The percentage of infants who died from RDS-The two comparative trials measured similar secondary

related causes within 14 days was also significantly lower in theendpoints.[20,21] These included all-cause mortality and incidence

lucinactant group than in the colfosceril palmitate group (4.7% vsof BPD, measured at day 28 and 36 weeks post-menstrual age

9.4%; OR 0.43, 95% CI 0.25, 0.73; p = 0.002).[20]

(PMA), as well as the incidence of complications of prematurity● The incidence of RDS at 24 hours did not differ significantly

including air leaks, intraventricular hemorrhage, periventricularbetween the lucinactant and beractant groups.[20] However, the

leukomalacia, retinopathy of prematurity, pulmonary hemorrhageincidence of RDS-related mortality within 14 days was signifi-

and sepsis.[20,21] Complications of prematurity reported in thesecantly lower in infants treated with lucinactant than in recipients of

trials are discussed in the tolerability section (see section 3).beractant (4.7% vs 10.5%; OR 0.35, 95% CI 0.18, 0.66; p =

Results from both trials were reported as rates of occurrence (%);0.001).[20]

some odds ratios (ORs) were also reported.[20,21]

● A greater proportion of infants were alive without BPD at 36Infants were excluded from participating in these two trials if

weeks PMA in the lucinactant-treated group compared with thethey had an Apgar score of less than three at 5 minutes after birth,

colfosceril palmitate group (59.4% vs 53.8%; p = 0.021) [figuremajor congenital malformations, or chromosomal abnormali-

1].[20] This was the only significant difference in secondaryties.[20,21] Infants who were delivered more than 2 weeks after the

endpoints and resulted from the combination of a reduction (non-rupture of membranes or who required resuscitation in the delivery

significant) in all-cause mortality and a significantly reducedroom with chest compressions, vasopressors, bicarbonate, or IV

frequency of BPD. Specifically, the incidence of BPD at 36 weeksfluids were also excluded.[20,21]

PMA was 40.2% in infants treated with lucinactant and 45.0% inBoth trials are continuing with 6- and 12-month follow-up those treated with colfosceril palmitate (OR 0.75, 95% CI 0.56,

clinical assessments for all enrolled infants.[22]0.99; p = 0.045).[20]

An earlier nonblind, dose-comparison study examined the effi- ● All treatment groups experienced improvements in oxygena-cacy of lucinactant (then known as KL4 surfactant) in the treat- tion. FiO2 and mean airway pressure requirements for respiratoryment of premature infants with RDS.[23] In this study, lucinactant support decreased over the 72 hours following treatment. Thiswas administered intratracheally to 39 eligible preterm infants decrease was greater in lucinactant recipients and beractant recipi-with birth weights of between 750g and 1750g who required ents at 24 hours than in recipients of colfosceril palmitate (quanti-mechanical ventilation for RDS. A low dose (133 mg/kg) of tative data not reported).[20] After 72 hours, the areas under thelucinactant was administered to the first eight patients and a high curve for FiO2 were 0.38 ± 0.19 and 0.37 ± 0.19 versus 0.40 ±



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LucinactantBeractantColfosceril palmitatePoractant alfa

SELECT STAR

Fig. 1. Efficacy of lucinactant and comparators in respiratory distress syndrome (RDS). Survival without bronchopulmonary dysplasia (BPD) at (a) 28 daysof age and (b) 36 weeks post-menstrual age (PMA) in two comparative trials.[20,21] Premature infants were randomized in two double-blind, active-controlled, multicenter trials to receive lucinactant 175mg phospholipids/kg birth weight, beractant 100 mg/kg, or colfosceril palmitate 67.5 mg/kg (SELECT,n = 1294[20]), or lucinactant 175 mg/kg or poractant alfa 175 mg/kg (STAR, n = 252[21]), intratracheally 20–30 minutes after birth to prevent or lessen thedevelopment of neonatal respiratory distress syndrome. BPD was defined as requiring mechanical ventilation or additional oxygen. SELECT = Safety andEffectiveness of Lucinactant vs Exosurf in a Clinical Trial of RDS in premature infants; STAR = Surfaxin Therapy Against RDS; * p < 0.05 vs colfoscerilpalmitate.

0.20, for lucinactant and beractant versus colfosceril palmitate (p ≤ with lucinactant had a mean Edwards’ RDS score of 2.0 ± 0.1,0.05).[20] down from a score of 3.7 ± 0.1 before treatment.[23]

● There were no statistically significant differences between the Comparison with Poractant Alfa (STAR)high- (200 mg/kg) and low-dose (133 mg/kg) groups in the mean● In the trial that compared lucinactant with poractant alfa,a/A O2 ratios, and no requirements to cross any infants over to37.8% of the lucinactant recipients were alive without BPD at dayanother surfactant following the predefined conditions for the trial.28, compared with 33.1% of the infants who received poractantHowever, several infants were subsequently given an alternativealfa, giving a treatment difference of 4.7% (95% CI –7.3, 16.8)surfactant either mistakenly or for other reasons.[23]

[figure 1]. The lower boundary of the treatment difference 95%confidence interval was greater than the prespecified limit of–14.5% which was required to show statistical non-inferiority.[21] 3. Tolerability● There were no significant differences between the two treat-

ment groups in all-cause mortality at day 28 and 36 weeks PMA or ● Lucinactant was generally well tolerated in the three trialsbeing alive without BPD at 36 weeks PMA.[21]

involving premature infants.[20,21,23] Adverse events reported dur-ing the lucinactant administration procedure were transient and

Dose-Comparison Trial similar to events reported with other surfactants (reviewed bySuresh and Soll[24]).

● Treatment with lucinactant improved pulmonary gas exchangein premature infants in the dose-comparison trial.[23] The levels of ● Infants who received lucinactant or beractant had significantlya/A O2 increased from a mean pretreatment value of 0.14 ± 0.02 to higher incidences of transient pallor during administration thana mean of 0.40 ± 0.04 within 12 hours after treatment. The median recipients of colfosceril palmitate (12.4% and 12.8% vs 7.1%; p <duration of mechanical ventilation was 5 days, and 34 (89.5%) of 0.05, lucinactant and beractant vs colfosceril palmitate).[20] The38 evaluable infants were extubated by day 28. No RDS-related incidences of other events were significantly higher (p < 0.05) fordeaths occurred during the study. The incidence of BPD was 4 lucinactant (but not beractant) than for colfosceril recipients.(10.8%) of 37 at 28 days. In this trial, BPD was diagnosed by an These events included transient dose interruption (11.8% andEdwards’ radiographic score ≥4 and a Toce clinical score ≥5. 9.7% vs 7.3%, lucinactant and beractant vs colfosceril palmitate)Chest radiographs taken approximately 10 hours after treatment and transient endotracheal obstruction (8.4% and 6.6% vs


144 Moen et al.

3.8%).[20] Incidences of endotracheal tube reflux were not signifi- air leak that can occur in newborn infants, associated with naturalcantly different between groups (25.2%, 20.9%, and 26.9%).[20] surfactants (typical relative risk 0.63, 95% CI 0.52, 0.76; typical

risk difference –0.05, 95% CI –0.07, –0.03).[3] However, this● The transient events reported included events occurring duringperiods of sham-air administration. A maximum of two additional difference was not significant in the prevention trial. A marginaldoses of colfosceril palmitate were administered at 12-hourly increase in the risk of intraventricular hemorrhage was associatedintervals, whereas for lucinactant and beractant, a maximum of with the natural surfactant used in the prevention trial, but not inthree additional doses were administered at 6-hourly intervals. To the treatment trials (only six trials reported on this complica-maintain blinding, doses of air were administered to the colfosceril tion).[3] In the recent trials, there were no differences betweenpalmitate group when treatment was not required.[20]

lucinactant and beractant[20] or poractant alfa[21] for the incidences● In infants treated with lucinactant or poractant alfa, there were of these events (figure 2).

no differences in the incidences of oxygen desaturation, brady-cardia, apnea, dose interruption, or any other adverse events

4. Dosage and Administrationobserved.[21]

● In the dose-comparison trial, transient events related to theFormal prescribing information for lucinactant is not yet availa-administration procedure, including bradycardia and changes in

ble. In the two recent phase III trials, lucinactant was administeredoxygen saturation, were reported.[23] There was no control group,via the endotracheal tube at a dose of 175mg phospholipids/kgbut the occurrence of these events was believed to be similar tobirth weight (5.8 mL/kg; 30 mg/mL).[20,21] Lucinactant was giventhat reported in trials of other surfactants in premature infants.[23]

as prophylactic treatment 20–30 minutes after birth. Doses were● There were no differences between lucinactant recipients anddivided into two[21] or four[20] aliquots and administered via acomparator recipients for the incidences of complications of pre-5-French end-hole catheter, passed through a valve, into the endo-maturity described in section 2 (figure 2).[20,21]

tracheal tube above the carina. Positive pressure inflation, either● The effects of animal-derived versus non-protein-containingmanual or mechanical, was used during administration of thesynthetic surfactant therapy on complications of prematurity havesurfactant.[20,21] A maximum of two[21] or three[20] identical addi-been described in a meta-analysis of eleven trials, one preventiontional doses could be administered if necessary at 6-hour intervalstrial and ten treatment trials.[3] The treatment trial meta-analysisfollowing the initial dose.showed a significantly reduced risk of pneumothorax, one type of

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Percentage of infants Percentage of infants

LucinactantPoractant alfa

LucinactantBeractantColfosceril palmitate

Fig. 2. The incidence of complications of prematurity with lucinactant and comparators in premature infants with respiratory distress syndrome (RDS).Premature infants were randomized in two double-blind, active-controlled, multicenter trials to receive (a) lucinactant 175mg phospholipids/kg birth weight,beractant 100 mg/kg, or colfosceril palmitate 67.5 mg/kg (SELECT, n = 1294[20]); or (b) lucinactant 175 mg/kg or poractant alfa 175 mg/kg (STAR, n =252[21]), intratracheally 20–30 minutes after birth to prevent or lessen the development of neonatal respiratory distress syndrome. Incidences of necrotizingenterocolitis, apnea, and patent ductus arteriosus are not shown for the SELECT trial (a) as only total incidences were reported (17%, 52%, and 37%).[20]

IVH = intraventricular hemorrhage; PVL = periventricular leukomalacia; ROP = retinopathy of prematurity; SELECT = Safety and Effectiveness ofLucinactant vs Exosurf in a Clinical Trial of RDS in premature infants; STAR = Surfaxin Therapy Against RDS.



14. Revak SD, Merritt TA, Cochrane CG, et al. Efficacy of synthetic peptide-contain-5. Lucinactant: Current Statusing surfactant in the treatment of respiratory distress syndrome in preterm infant

rhesus monkeys. Pediatr Res 1996 Apr; 39 (4 Pt 1): 715-24

15. Nutt M, Patel N, Rairkar M, et al. Comparison of the novel lung surfactantThe US FDA has issued an approvable letter for lucinactant forsurfaxin® (lucinactant) with currently available commercial products [abstractthe prevention of RDS in premature infants. In two well controlledno. 2912]. Pediatric Academic Societies’ Annual Meeting; 2004 May 1-4; San

trials for this indication, lucinactant has shown clinical efficacyFrancisco

similar to that of animal-derived surfactants and superior to that of16. Merritt TA, Amirkhanian JD, Helbock H, et al. Reduction of the surface-tension-

a non-protein-containing synthetic surfactant. Lucinactant was lowering ability of surfactant after exposure to hypochlorous acid. Biochem J

generally well tolerated and had a safety and tolerability profile 1993 Oct 1; 295: 19-22

comparable to other exogenous surfactants. 17. Manalo E, Merritt TA, Kheiter A, et al. Comparative effects of some serum

components and proteolytic products of fibrinogen on surface tension-lowering

abilities of beractant and a synthetic peptide containing surfactant KL4. Pediatr

Res 1996 Jun; 39 (6): 947-52References

18. Sood SL, Balaraman V, Finn KC, et al. Exogenous surfactants in a piglet model of1. Boyd S. Causes and treatment of neonatal respiratory distress syndrome. Nurs

acute respiratory distress syndrome. Am J Respir Crit Care Med 1996 Feb; 153:Times 2004 Jul; 100 (30): 40-4820-8

2. Lewis JF. Surfactant: where are we in 2003? Can Respir J 2004; 11 (3): 204-619. Merritt TA, Kheiter A, Cochrane CG. Positive end-expiratory pressure during KL43. Suresh GK, Soll RF. Lung surfactants for neonatal respiratory distress syndrome:

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