Analgesia, Fentanyl, Infant, Newborn, Infant, Premature, Intranasal Drug Administration, Neonatal Intensive Care Units, Neonatal Pain, Pain Management, Retinopathy of Prematurity (ROP)
Conditions
Keywords
intranasal fentanyl, fentanyl, neonatal analgesia, procedural pain, ROP screening, Retinopathy of Prematurity, Preterm infants, Premature infants, infant pain, Non-invasive analgesia, Opioid analgesia, Intranasal drug delivery, Neonatal intensive care, NICU, Pain management in neonates, Infant procedural sedation
Brief summary
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
DRUGFentanyl 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.
DRUGNormal 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.
Sponsors
Marsha Campbell-Yeo
Canadian Institutes of Health Research (CIHR)
Dalhousie University
IWK Health Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a quadruple-masked (participant/family, care provider, investigator, and outcome assessor) randomized controlled trial. Blinding is maintained through pharmacy-controlled randomization and preparation of identical syringes containing either intranasal fentanyl or intranasal 0.9% normal saline placebo. Study drug and placebo are matched for volume, appearance, labeling, and administration method using a mucosal atomization device. Clinical staff administering the intervention, investigators, outcome assessors scoring PIPP-R from video recordings, and families remain unaware of treatment allocation throughout the trial. Allocation concealment is ensured by the institutional pharmacy, which maintains the randomization sequence and dispenses study medication according to assignment.
Intervention model description
This is a randomized, double-blind, placebo-controlled, parallel-group trial. Eligible preterm infants born ≤31 weeks gestational age and/or with birth weight \<1250 g who are undergoing routine retinopathy of prematurity (ROP) screening will be randomly assigned in a 1:1 ratio to receive either intranasal fentanyl or intranasal 0.9% normal saline placebo administered 10 minutes prior to the procedure. Participants will receive a single study intervention and will remain in their assigned treatment group throughout the study. The primary aim is to evaluate the analgesic efficacy and safety of intranasal fentanyl compared with placebo during ROP screening.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity during ROP screening | First 30 seconds after speculum insertion during ROP screening | Pain intensity will be measured using the Premature Infant Pain Profile-Revised (PIPP-R). The primary endpoint is the PIPP-R score during the first 30 seconds following speculum insertion during the ROP examination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of infants with low to mild pain | During procedure and at 1- and 5-minutes post-procedure | The proportion of infants experiencing low or mild pain will be determined using PIPP-R score thresholds (≤6), assessed by blinded coders from synchronized video recordings during and following the ROP examination. |
| Ongoing pain response during ROP screening | Every 30 seconds during the procedure | Pain response will be assessed using PIPP-R scores measured at 30-second intervals from speculum insertion until completion of the ROP examination, coded from synchronized video by blinded assessors. |
| Pain recovery following ROP screening | 1-minute and 5-minutes post-procedure | Pain recovery will be evaluated using PIPP-R scores measured at 1 and 5 minutes following completion of the ROP examination to assess resolution of pain. |
| Cry duration | From speculum insertion through 5 minutes post-procedure | Total cry duration (in seconds) will be measured from synchronized video recordings during the ROP examination and recovery period by trained, blinded assessors. |
| Salivary cortisol response | 20 minutes pre-procedure and 20 minutes post-procedure | Salivary cortisol will be measured as a biologic marker of stress response, collected at baseline (20 minutes pre-procedure) and 20 minutes post-procedure to assess change from baseline. |
| Adverse events | During the procedure and up to 4 hours post-intervention | Safety will be evaluated by monitoring predefined adverse events including apnea, bradycardia, hypotension, chest wall rigidity, oxygen desaturation, and requirement for airway support following intranasal administration. |
| Duration of ROP examination | During the procedure | Total duration of the ROP examination will be measured in seconds from speculum insertion to removal using timestamped video recordings. |
| Physiological responses | Baseline, during the procedure, and at 1- and 5-minutes post-procedure | Physiological parameters including heart rate, respiratory rate, oxygen saturation, and blood pressure will be recorded as indicators of physiological response to the procedure, using synchronized bedside monitoring data. |
Countries
Canada
Contacts
CONTACTHelen McCord, BScN, MN, PhD Candidate, NNP
Outcome results
None listed