Fentanyl Intranasal for Retinopathy of Prematurity Screening in Preterm Infants

Official title

Intranasal Fentanyl to Reduce Pain Intensity Associated With Retinopathy of Prematurity Screening in Preterm Infants: A Randomized Control Trial

Overview

The goal of this clinical trial is to learn whether intranasal fentanyl (a pain medicine given as a nasal spray) can reduce pain and is safe to use during routine eye examinations for retinopathy of prematurity (ROP) in preterm infants. ROP is an eye condition that can affect babies born too early and requires regular eye examinations. The main questions this study aims to answer are: Does intranasal fentanyl lower pain during ROP screening? Is intranasal fentanyl safe for preterm infants? Researchers will compare intranasal fentanyl with a placebo (a saltwater spray that contains no medicine) to determine whether the medicine lowers pain during ROP screening. Participants will receive either intranasal fentanyl or placebo before their routine ROP eye examination, in addition to the standard comfort measures normally used during the procedure. Researchers will measure participants' pain and monitor their heart rate, oxygen levels, and any side effects during and after the examination.

Detailed description

Retinopathy of prematurity (ROP) screening is an essential part of the care of preterm infants. Despite the routine use of standard comfort measures, the examination remains associated with moderate-to-high pain intensity scores in many infants. Repeated exposure to untreated or undertreated procedural pain in preterm infants has been associated with adverse short- and long-term effects, highlighting the need for additional evidence-based pain management strategies.

Intranasal fentanyl has several characteristics that make it a promising option for procedural pain management. It has a rapid onset of action, is easy to administer, avoids the need for intravenous access, and has been shown to be effective and well tolerated for procedural pain in older infants and children. Emerging neonatal evidence, including randomized controlled trials, suggests that intranasal fentanyl may reduce pain during ROP screening, but additional high-quality evidence is needed to establish its effectiveness and safety in preterm infants.

This randomized, double-blind, placebo-controlled clinical trial will evaluate whether intranasal fentanyl, when used in addition to standard comfort measures, reduces pain during routine ROP screening while maintaining an acceptable safety profile. The study is designed to provide high-quality evidence to help determine whether intranasal fentanyl should be considered as an additional option for pain management during this necessary neonatal procedure.

The findings from this study may help improve pain management for preterm infants undergoing ROP screening and contribute to future evidence-based clinical practice guidelines for neonatal procedural pain management.

Interventions

• Drug Fentanyl Citrate (Intranasal)
  Fentanyl citrate will be administered intranasally at a dose of 2 mcg/kg via a mucosal atomization device 10 minutes prior to retinopathy of prematurity (ROP) screening. The intervention will be delivered into one nostril. All participants will also receive standard comfort measures as part of routine NICU care, including oral sucrose, non-nutritive sucking, swaddling, and topical anesthetic eye drops.
• Drug Normal Saline (Placebo, Intranasal)
  An equivalent volume of intranasal 0.9% normal saline placebo will be administered via a mucosal atomization device 10 minutes prior to retinopathy of prematurity (ROP) screening. All participants will also receive standard comfort measures as part of routine NICU care, including oral sucrose, non-nutritive sucking, swaddling, and topical anesthetic eye drops.

Primary outcome measures

• Pain intensity during ROP screening [Time frame: First 30 seconds after speculum insertion during ROP screening]

Secondary outcome measures (8)

• Proportion of infants with low to mild pain [Time frame: During procedure and at 1- and 5-minutes post-procedure]
• Ongoing pain response during ROP screening [Time frame: Every 30 seconds during the procedure]
• Pain recovery following ROP screening [Time frame: 1-minute and 5-minutes post-procedure]
• Cry duration [Time frame: From speculum insertion through 5 minutes post-procedure]
• Salivary cortisol response [Time frame: 20 minutes pre-procedure and 20 minutes post-procedure]
• Adverse events [Time frame: During the procedure and up to 4 hours post-intervention]
• Duration of ROP examination [Time frame: During the procedure]
• Physiological responses [Time frame: Baseline, during the procedure, and at 1- and 5-minutes post-procedure]

Eligibility criteria

Inclusion criteria

• Preterm infants born ≤31 weeks gestational age and/or with birth weight <1250 g
• Scheduled to undergo routine retinopathy of prematurity (ROP) screening as part of standard NICU care
• Clinically stable at the time of screening, defined as not requiring acute resuscitative support (no bag-mask ventilation, intubation, or chest compressions within the preceding 24 hours) and maintaining stable cardiorespiratory parameters on baseline respiratory support
• Written informed consent obtained from a parent or legally authorized representative

Exclusion criteria

• Congenital anomalies or conditions affecting the nasal passages that would interfere with intranasal drug administration
• Receipt of systemic opioids, benzodiazepines, barbiturates, or other sedative/analgesic medications within 24 hours prior to the ROP examination
• Known hypersensitivity or prior adverse reaction to fentanyl

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• IWK Health — Halifax

Publications

• McCord H, Disher T, Promelle V, Mitra S, Singh B, Bruce C, Peckham C, Neil E, Campbell-Yeo M. Intranasal fentanyl to reduce pain intensity associated with retinopathy of prematurity screening in preterm infants: study protocol for a randomized controlled trial. BMC Pediatr. 2026 Jul 15. doi: 10.1186/s12887-026-07328-x. Online ahead of print. PMID 42458331

Identifiers

NCT: NCT07112430 · IWK_INF_PainTrial2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗