Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial

Stefan Minocchieri, Clare A Berry, J Jane Pillow, CureNeb Study Team, Stefan Minocchieri, Clare A Berry, J Jane Pillow, CureNeb Study Team

Abstract

Objective: To evaluate if nebulised surfactant reduces intubation requirement in preterm infants with respiratory distress treated with nasal continuous positive airway pressure (nCPAP).

Design: Double blind, parallel, stratified, randomised control trial.

Setting: Sole tertiary neonatal unit in West Australia.

Patients: Preterm infants (290-336 weeks' gestational age, GA) less than 4 hours of age requiring 22%-30% supplemental oxygen, with informed parental written consent.

Interventions: Infants were randomised within strata (290-316 and 320-336 weeks' GA) to bubble nCPAP or bubble nCPAP and nebulised surfactant (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation (100 mg/kg) was repeated after 12 hours for persistent supplemental oxygen requirement.

Main outcome measures: The primary outcomes were requirement for intubation and duration of mechanical ventilation at 72 hours. Data analysis followed the intention-to-treat principle.

Results: 360 of 606 assessed infants were eligible; 64 of 360 infants were enrolled and randomised (n=32/group). Surfactant nebulisation reduced the requirement for intubation within 72 hours: 11 of 32 infants were intubated after continuous positive airway pressure (CPAP) and nebulised surfactant compared with 22 of 32 infants receiving CPAP alone (relative risk (95% CI)=0.526 (0.292 to 0.950)). The reduced requirement for intubation was limited to the 320-336 weeks' GA stratum. The median (range) duration of ventilation in the first 72 hours was not different between the intervention (0 (0-62) hours) and control (9 (0-64) hours; p=0.220) groups. There were no major adverse events.

Conclusions: Early postnatal nebulised surfactant may reduce the need for intubation in the first 3 days of life compared with nCPAP alone in infants born at 290-336 weeks' GA with mild respiratory distress syndrome. Confirmation requires further adequately powered studies.

Trial registration number: ACTRN12610000857000.

Keywords: infant, premature; nebulization; respiratory distress syndrome; surfactant.

Conflict of interest statement

Competing interests: JJP receives unrestricted grants of surfactant product from Chiesi Farmaceutici SpA (Parma, Italy) for unrelated neonatal ventilation research in preterm lambs. Surfactant for the current study was purchased from the hospital pharmacy at retail price using grant funding described above. JJP has also received equipment and unrestricted grant funding from Fisher & Paykel for unrelated preterm lamb research in the past. SM has a conflict of interest as disclosed above in relation to his patent with PARI Pharma.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials diagram for study recruitment and treatment assignment. CPAP, continuous positive airway pressure; FiO2, fractional inspired oxygen; GA, gestational age.
Figure 2
Figure 2
Kaplan-Meier survival curves illustrating the temporal relation between the treatment assignment and the probability of remaining on nCPAP all infants (top); 29.0-31.6 w gestation stratum (middle); and c) 32.0-33.6 w gestation stratum (bottom). Solid circles: nCPAP only; open triangles:  nCPAP+nebulised surfactant. Infants were more likely to remain on CPAP if they received nebulised surfactant. Stratified analysis indicated a significant benefit of nebulised surfactant was restricted to the more mature gestational age group. CPAP, continuous positive airway pressure; GA, gestational age; nCPAP, nasal continuous positive airway pressure.

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