By Reuters Staff
NEW YORK (Reuters Health) - Delivery of aerosolized calfactant, a type of surfactant, reduced the need for intubation for liquid surfactant by nearly 50% in a large randomized controlled trial of newborns with respiratory distress syndrome (RDS).
"As a result, far fewer infants in the aerosol group were subjected to the potential harms of laryngoscopy and intubation," Dr. James Cummings from Albany Medical College in New York and the AERO-02 study team reports in a paper in Pediatrics today.
They note that currently, exogenous surfactants for RDS are approved for tracheal instillation only, which requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have yielded mixed results.
The new study enrolled 457 newborns (median gestation, 33 weeks; median birth weight, 1960 grams) with signs of mild to moderate RDS requiring noninvasive respiratory support; 230 were randomly allocated to aerosolized calfactant delivered directly into the mouth via a nebulizer modified with a pacifier adapter. Infants in the aerosol group received up to three treatments at least four hours apart.
The 227 infants in the control group received usual care, determined by providers. In cases of persistent or worsening respiratory distress, infants were intubated and given instilled surfactant at the providers' discretion.
Rates of intubation for surfactant instillation within the first four days of life (primary outcome) were 26% in the aerosol group and 50% in the usual care group (P<0.0001), with a relative risk of 0.51 (90% CI: 0.41 to 0.63) and five the number needed to treat to prevent one intubation, the investigators report. There were no between-group differences in respiratory outcomes up to 28 days of age.
Limitations of the study include inclusion of relatively few infants born at less than 28 weeks gestation and the unblinded study design. Also, because chest x-rays were not required, it's possible that some infants may have had etiologies other than RDS.
Despite these limitations, this study shows that aerosolized calfactant can be readily administered to newborns with mild to moderate RDS and reduces the need for intubation and liquid surfactant instillation during the first four days of age, the investigators say.
"The use of aerosolized calfactant avoids the risks associated with endotracheal intubation and expands opportunities for surfactant therapy in the hospitalized patient," they add.
The co-authors of a linked editorial say the results are "promising" and in line with previous pilot studies and a recent phase 1 clinical study that demonstrated the feasibility and safety of aerosolized surfactants for newborns receiving noninvasive ventilation.
"Nebulization of surfactants remains an attractive route because it avoids endotracheal manipulation, with the potential of reducing exposure to mechanical ventilation and, ultimately, decreasing the risk of lung injury," write Dr. Kirsten Glaser, University of Leipzig, Germany and Dr. Clyde Wright, Children's Hospital Colorado, Aurora.
"Although this study is promising and reveals safety and feasibility, a trial targeted at a less mature population is necessary before adopting this approach for preterm infants at highest risk of lung injury," they caution.
The study was funded by ONY Biotech, manufacturer of Infasurf, the surfactant used in the trial. Three study investigators have financial relationships with ONY Biotech. Dr. Cummings did not respond to a request for comment by press time.
SOURCE: https://bit.ly/3nUboxs and https://bit.ly/2H3GGkT Pediatrics, online October 15, 2020.