Intranasal Fentanyl in Preterm Infants Undergoing Peripherally Inserted Central Catheter Placement (INFENT PICC): A Feasibility Randomized Controlled Trial

<b>Background/Objectives</b>: Preterm infants in the neonatal intensive care unit (NICU) are subjected to clinically essential painful procedures including peripherally inserted central catheter (PICC) placement. Pharmacological interventions are inconsistently used for procedural analgesia due to concerns of adverse events. Intranasal (IN) fentanyl is a promising pharmacological alternative that delivers rapid targeted analgesia. The objectives of this blinded randomized controlled trial (RCT) were to assess the feasibility of conducting a definitive RCT of IN fentanyl for PICC placement in preterm infants and evaluate the acceptability and adoption of IN fentanyl for procedural pain management in the NICU. <b>Methods</b>: Infants admitted to the NICU (Mount Sinai Hospital, Toronto) with a gestational age (GA) at birth < 32 weeks undergoing their first PICC placement were randomized to IN fentanyl or placebo as an add-on to standard of care. The primary feasibility outcomes were recruitment and completeness of data collection for pain assessment. The pre-specified targets were recruitment of 24 participants and at least 80% of video-recordings being suitable for pain assessment. Secondary outcomes were adverse events, and IN fentanyl acceptability and adoption by healthcare providers. (ClinicalTrials.gov ID NCT06590870). <b>Results</b>: Between August 2024 and January 2025, 16 parents/guardians were approached resulting in eight enrollments for a consent rate of 50% (95% CI 28, 72). The target recruitment of 24 participants was not achieved. Out of six infants that received study interventions, all video-recordings were suitable for pain assessment by outcome assessors with a success rate of 100% (95% CI 61, 100). There were no adverse events. Fifteen healthcare providers completed the survey and reported acceptability of IN fentanyl but barriers with its adoption in clinical practice. <b>Conclusions</b>: Major modifications to the recruitment strategy would be required to progress to a definitive RCT. Strategies facilitating IN fentanyl adoption for procedural analgesia in the NICU are needed.