Aerosolized Calfactant for Newborns With Respiratory Distress: A Randomized Trial

Pediatrics. 2020 Nov;146(5):e20193967. doi: 10.1542/peds.2019-3967. Epub 2020 Oct 15.

Abstract

Background: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant.

Methods: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion.

Results: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different.

Conclusions: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

Trial registration: ClinicalTrials.gov NCT03058666.

Publication types

  • Multicenter Study
  • Pragmatic Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aerosols
  • Biological Products / administration & dosage*
  • Cohort Studies
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Intensive Care Units, Neonatal / statistics & numerical data
  • Intubation, Intratracheal / statistics & numerical data
  • Male
  • Nebulizers and Vaporizers
  • Prospective Studies
  • Pulmonary Surfactants / administration & dosage*
  • Respiratory Distress Syndrome, Newborn / drug therapy*

Substances

  • Aerosols
  • Biological Products
  • Pulmonary Surfactants
  • calfactant

Associated data

  • ClinicalTrials.gov/NCT03058666