442 - Predictors of Successful Treatment of Respiratory Distress with Aerosolized Calfactant

Poster Number: 442
Publication Number: 442.227

Michelle Hojnicki, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States; Stephen Minton, University of Utah School of Medicine, Provo, UT, United States; George Albert, Buffalo Neonatology Associates, Buffalo, NY, United States; Dinushan C. Kaluarachchi, University of Wisconsin - Madison, Madison, WI, United States; Prem Fort, Johns Hopkins All Children's Hospital, St Petersburg, FL, United States; Ann Ross, K. Hovnanian Children's Hospital at Jersey Shore University Medical Center, Neptune, NJ, United States; Gregory E. Wilding, University at Buffalo, Buffalo, NY, United States; Laura Richards, Jackson-Madison County General Hospital, Jackson, TN, United States; Scott O. Guthrie, Monroe Carell Jr. Children's Hospital at Vanderbilt, Jackson, TN, United States

Background: Respiratory distress syndrome (RDS) often leads to intubation for surfactant. Less invasive methods for delivery can improve the success of non-invasive ventilation. The AERO-02 trial investigated a device to aerosolize calfactant which reduced the need for intubation by ~50% in infants with mild to moderate RDS. A continued use protocol, AERO-03 (NCT03582930), has allowed expanded access to the device while the FDA reviews. No study has identified criteria to predict the success of aerosolized calfactant which would help identify candidates for treatment.

Objective: Identify predictors for successful aerosolized calfactant treatment among infants enrolled in the AERO-02 trial and the AERO-03 continued use protocol.

Design/Methods: IRB granted waiver of consent. Factors from AERO-02 and AERO-03 including gestational age (GA), birthweight (BW), sex, time of first aerosol administration, total doses required, respiratory support (support type, level of support, and FiO2 requirement) at time of treatment, and need for intubation were assessed using Fisher’s exact test or the Wilcoxon rank sum test. Univariate and multivariate associations between intubation and covariates were examined using logistic regression from which estimated ORs were produced.

Results: A total of 401 infants (226 from AERO-02 and 175 from AERO-03) were included. The following characteristics were significantly different between two trials: sex, support type, BW, GA, and number of aerosols. [Table 1] 87 infants (22%) required intubation. On univariate testing, successful aerosolized treatment was associated with BW (p=0.003), GA (p=0.0003), number of aerosols (p < 0.0001), and FiO2 (p= 0.0001). Mode of support in both datasets was primarily CPAP. Multivariate analysis of infants on CPAP showed the following factors to be associated with need for intubation:  higher PEEP (p=0.01), need for more than 1 aerosol (p < 0.0001), higher FiO2 (p=0.002), and lower GA (p=0.02). [Fig. 1] No between-study differential effects were identified. Stepwise regression determined that four factors could predict aerosol success and avoidance of intubation: GA, number of aerosols, FiO2, and CPAP PEEP (AUC=0.7824). [Fig. 2]Conclusion(s): Continued use of aerosolized calfactant demonstrates that it is likely to prevent intubation in neonates with specific clinical criteria which can predict success. Once an FDA approved device is available, use expands, and clinicians gain further experience, it is expected that these criteria will be better defined. A method to track clinical use to guide therapeutic decisions will help with successful implementation.
Table 1Characteristics of the study cohort. Mean (SD) or N (%) shown.
Figure 1Odds Ratios with 95% CI for all factors in multivariate analysis on cohort of infants on CPAP.