Intervention, Allocation, and Blinding
Each aerosolized therapy (albuterol 1.25 mg, albuterol 2.5 mg, and 3mL saline placebo) was administered every 4 hours for up to a total of 6 doses during separate 24-hour treatment periods. A 6-hour washout phase was utilized after each 24-hour treatment period before initiating the subsequent trial therapy. A 6-hour monitoring period was used following the final treatment at the end of each infant’s trial. The placebo and study drugs were administered in-line to the ventilator circuitry via the Aeroneb® Pro vibrating mesh nebulizer (Aerogen®, Galway, Ireland) placed on the inspiratory limb on the dry side of the humidifier, as is the standard practice in our institution.
The order of the three 24-hours treatment periods was randomly assigned in each infant. Briefly, each study participant was assigned to 1 of 6 possible treatment sequences using block randomization (block sizes of 6) in a 1:1 ratio. The randomization sequence was generated using the “ralloc” function in Stata version 13.1. All study randomization and drug preparation procedures were performed by CHOP Investigational Pharmacy to maintain blinding of the study investigators, clinicians, and families. Each study medication dose and saline placebo was drawn up in a 3ml syringe to an equivalent final volume. The two albuterol doses and saline placebo were not visually distinguishable. All six doses administered during a treatment period were delivered to the participant’s bedside in a brown, light protected bag labeled with the appropriate treatment order number (1, 2, or 3).