Curosurf®
KEY CUROSURF REFERENCES
- Composition
- Pilot Trial
- The First Randomized
Trial
- Single versus Multiple
Doses
- High versus Low
Doses
- Early versus Late
Treatment
- Prophylaxis versus
Rescue Treatment
- Curosurf and CPAP
- Follow-up Study
- Comparative Trials
1.
Composition
Robertson B, Curstedt T, Johansson J, Jornvall H, Kobayashi T.
Structural and functional characterization of porcine surfactant isolated
by liquid-gel chromatography.
Progress in Respiration Research 1990; 25: 237-246.
This paper outlines the preparation of Curosurf
from minced porcine lungs and characterizes its composition. There is information
on the surface properties of Curosurf in vitro and physiological effects in
immature newborn rabbits. This paper also discusses inactivation of Curosurf
by serum proteins and potential immunogenicity of surfactant proteins.
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2.
Pilot Trial
Noack G, Berggren P, Curstedt T, Grossmann G, Herin P, Mortensson W, Nilsson
R, Robertson B.
Severe neonatal respiratory distress syndrome treated with the isolated
phospholipid fraction of natural surfactant.
Acta Paediatrica Scandinavica 1987; 76: 697-705. (PubMed)
This paper reports the outcome of 10 preterm
babies with severe respiratory distress syndrome (RDS) who were treated with
Curosurf at St Goran's Hospital in Stockholm. There was a rapid improvement
in arterial oxygen tensions after treatment and aeration of chest radiographs
increased within 2 hours. The paper describes the preparation of Curosurf in
some detail and it is interesting to note that the first 7 babies treated were
given a bovine derived surfactant whilst the last 3 had the now better known
porcine surfactant.
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3.
The First Randomized Trial
Collaborative European Multicenter Study Group.
Surfactant replacement therapy for severe neonatal respiratory distress
syndrome: an international randomized clinical trial.
Pediatrics 1988; 82: 683-691. (PubMed)
This study showed that Curosurf given in a
dose of 200 mg/kg to treat severe RDS had a number of beneficial effects. In
addition to dramatic improvement in oxygenation within 5 minutes there was increased
survival and a reduction of pulmonary air leaks in the treated infants. When
it was published in 1988 this study was the first to have shown improved survival
with surfactant treatment. It lead to a series of further randomized trials
assessing repeat dosing, total dose and timing of surfactant treatment (see
4, 5,
6 and 7).
Two year follow up was also reported (see 9).
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4.
Single versus Multiple Doses
Speer CP, Robertson B, Curstedt T, Halliday HL, Compagnone D, et al.
Randomized European multicenter trial of surfactant replacement therapy
for severe neonatal respiratory distress syndrome: single versus multiple doses
of Curosurf.
Pediatrics 1992; 89: 13-20. (PubMed)
This large trial showed better outcomes for
preterm babies with severe RDS treated with multiple doses as opposed to a single
dose of Curosurf. Both groups received an initial dose of 200 mg/kg but the
multiple dose group were able to receive 2 further doses of 100 mg/kg each if
they still needed artificial ventilation in more than 21% oxygen 12 and 24 hours
later. The multiple dose group had better survival and a reduced rate of pneumothorax
compared to the single dose group.
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5.
High versus Low Doses
Halliday HL, Tarnow-Mordi WO, Corcoran JD, Patterson CC on behalf of the European
Collaborative Multicentre Study Group.
Multicentre randomised trial comparing high and low dose surfactant
regimens for the treatment of respiratory distress syndrome (the Curosurf 4
trial).
Archives of Disease in Childhood 1993; 69: 276-280. (PubMed)
Over 2000 preterm infants with severe RDS
were enrolled in this study which compared a cumulative total dose of Curosurf
of up to 600 mg/kg with up to 300 mg/kg. Those given an initial dose of 200
mg/kg had better indices of oxygenation up to 36 hours after treatment compared
to those given an initial dose of 100 mg/kg. However, the primary endpoints
of survival without chronic oxygen dependency at either 28 days or expected
date of delivery were similar in both dosage groups.
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6.
Early versus Late Treatment
Bevilacqua G, Halliday HL, Parmigiani S, Robertson B.
Randomized multicentre trial of treatment with porcine natural surfactant
for moderately severe neonatal respiratory distress syndrome.
Journal of Perinatal Medicine 1993; 21: 329-340. (PubMed)
This study reported the benefits of treating
infants with RDS when their oxygen requirements are between 40 and 60% compared
to greater than 60%. Treatment at an earlier stage improves survival and reduces
the risk of intraventricular haemorrhage.
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7.
Prophylaxis versus Rescue Treatment
Egberts J, Brand R, Walti H, Bevilacqua G, Breart G, Gardini F.
Mortality, severe respiratory distress syndrome, and chronic lung disease
of the newborn are reduced more after prophylactic than after therapeutic administration
of the surfactant Curosurf.
Pediatrics 1997; 100: E4. (PubMed)
This paper reports on a meta-analysis of 3
prophylaxis (treatment within 0-15 minutes of birth) versus rescue (treatment
when criteria for moderately severe RDS were met) trials (Egberts J, de Winter
P, Sedin G, de Kleine MJK, Broberger U, van Bel F, Curstedt T, Robertson B.
Comparison of prophylaxis and rescue treatment with Curosurf in neonates less
than 30 weeks' gestation: a randomized trial. Pediatrics 1993; 92: 768-774
- PubMed.
Walti H, Paris-Llado J, Breart G, Couchard M and the French Collaborative Study
Group. Porcine surfactant replacement therapy in newborns of 25-31 weeks' gestation:
a randomized, multicentre trial of prophylaxis versus rescue with multiple low
doses. Acta Paediatrica 1995; 84: 913-921 - PubMed
Bevilacqua G, Parmigiani S, Robertson B and the Italian Collaborative Multicenter
Group. Prophylaxis of respiratory distress syndrome by treatment with modified
porcine surfactant at birth: a multicenter prospective randomized trial. Journal
of Perinatal Medicine 1996; 24: 609-620 - PubMed.).
For infants of less than 31 weeks' gestation prophylaxis with Curosurf leads
to improved outcomes including survival, chronic lung disease and intraventricular
haemorrhage (Walti H, Paris-Llado J, Egberts J, Brand R, Bevilacqua G, Gardini
F, Breart G. Prophylactic administration of porcine-derived lung surfactant
is a significant factor in reducing the odds for peri-ventricular haemorrhage
in premature infants. Biology of the Neonate 2002; 81: 182-187 - PubMed.).
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8.
Curosurf and CPAP
Verder H, Robertson B, Greisen G, Ebbesen F, Albertsen P, Lundstrom K, Jacobsen
T for the Danish-Swedish Multicenter Study Group.
Surfactant therapy and nasal continuous positive airway pressure for
newborns with respiratory distress syndrome.
New England Journal of Medicine 1994; 331: 1051-1055. (PubMed)
Verder H, Albertsen P, Ebbesen F, Greisen
G, Robertson B, Bertelsen A, Agertoft L, Djernes B, Nathan E, Reinholt J.
Nasal continuous positive airway pressure and early surfactant therapy
for respiratory distress syndrome in newborns of less than 30 weeks' gestation.
Pediatrics 1999; 103: E24. (PubMed)
These 2 randomized trials showed that the
combination of Curosurf treatment and nasal continuous positive airway pressure
(CPAP) reduced the need for subsequent mechanical ventilation. For infants of
less than 30 weeks' gestation early treatment with Curosurf combined with CPAP
was very effective.
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9.
Follow-up Study
Robertson B, Curstedt T, Tubman R, Strayer D, Berggren P, et al.
A 2-year follow up of babies enrolled in a European multicentre trial
of porcine surfactant replacement for severe neonatal respiratory distress syndrome.
European Journal of Pediatrics 1992; 151: 372-376. (PubMed)
This paper reported 1 and 2 year outcomes
for surviving babies from the first randomized trial (see 3).
Treated and control infants were similar as regards physical growth, prevalence
of respiratory symptoms and occurrence of major and minor disabilities when
examined at 1 and 2 years of age. Surfactant treatment for severe RDS reduces
mortality and pulmonary leaks and is not associated with an increase in disability
at 2 years of age.
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10.
Comparative Trials
Speer CP, Gefeller O, Groneck P, Laufkotter E, Roll C, Hanssler L, et al.
Randomised clinical trial of two treatment regimens of natural surfactant
preparations in neonatal respiratory distress syndrome.
Archives of Disease in Childhood 1995; 72: F8-F13. (PubMed)
Ramanathan R, Rasmussen MR, Gerstmann D, Finer
N, Sekar K and the North American Study Group.
A randomized, multicenter masked comparison trial of Curosurf and Survanta
in the treatment of respiratory distress syndrome in preterm infants.
Biology of the Neonate 2002; 81 (suppl 1): 36 (abstract 16).
Baroutis G, Kaleyias J, Liarou T, Papathoma
E, Hatzistamatiou Z, Costalos C.
Comparison of three treatment regimens of natural surfactant preparations
in neonatal respiratory distress syndrome.
European Journal of Pediatrics 2003; 162: 476-480. (PubMed)
Kukkonen AK, Virtanen M, Jarvenpaa A-L, Pokela
M-L, Ikonen S, Fellman V.
Randomized trial comparing natural and synthetic surfactant: increased
infection rate after natural surfactant?
Acta Paediatrica 2000; 89: 556-561. (PubMed)
Ainsworth SB, Beresford MW, Milligan DWA,
Shaw NJ, Matthews JNS, Fenton AC, Ward Platt MP.
Pumactant and poractant alfa for treatment of respiratory distress syndrome
in neonates born at 25-29 weeks' gestation: a randomised trial.
Lancet 2000; 355: 1387-1392. (PubMed)
There are 5 trials where Curosurf has been
compared with other surfactants. In 2 studies there was a direct comparison
with Survanta (a bovine surfactant), in 1 the comparison was with Survanta and
Alveofact (another bovine surfactant) and in 2 studies the comparator was a
synthetic surfactant (Exosurf in 1 and pumactant or ALEC in the other). Curosurf
was shown to more rapidly improve lung function in preterm babies with RDS when
compared with Survanta. There were also trends towards better survival in the
babies treated with Curosurf. In the 3 group comparison study the Curosurf and
Alveofact groups spent fewer days on the ventilator, needed fewer days of oxygen
and were in hospital for shorter periods than the Survanta treated babies. When
compared to Exosurf babies treated with Curosurf had lower inspired oxygen concentrations
and mean airway pressures but there were no other major differences between
the groups. On the contrary babies of 25 to 29 weeks' gestation treated with
Curosurf soon after birth had much better survival rates than those treated
with ALEC (pumactant).
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