Fentanyl Intranasal for Retinopathy of Prematurity Screening in Preterm Infants
- Conditions
- Neonatal PainRetinopathy of Prematurity (ROP)Infant, NewbornPain ManagementFentanylNeonatal Intensive Care UnitsAnalgesiaInfant, PrematureIntranasal Drug Administration
- Interventions
- Drug: Fentanyl Citrate (Intranasal)Drug: Normal Saline (Placebo, Intranasal)
- Registration Number
- NCT07112430
- Lead Sponsor
- IWK Health Centre
- Brief Summary
This single-center, double-blinded, randomized controlled trial aims to evaluate the efficacy and safety of intranasal fentanyl (INF) for reducing pain during retinopathy of prematurity (ROP) screening in preterm infants. The trial will enroll preterm neonates (≤32 weeks gestation) requiring ROP screening and randomize them to receive either intranasal fentanyl (2 mcg/kg) or a placebo (normal saline) 5-10 minutes prior to the procedure. The primary outcome is pain intensity measured using the Premature Infant Pain Profile-Revised (PIPP-R) at 30 seconds after speculum insertion. Secondary outcomes include physiological (heart rate, oxygen saturation), behavioral (crying time), and recovery indicators, along with adverse events and need for rescue dosing. This study addresses a critical gap in evidence by exploring a non-invasive pharmacologic intervention for procedural pain in the neonatal intensive care unit (NICU) setting. The findings may inform future practice and guidelines for neonatal pain management.
- Detailed Description
This double-blinded, randomized controlled trial will evaluate the effectiveness and safety of intranasal fentanyl (INF) in reducing procedural pain associated with retinopathy of prematurity (ROP) screening in preterm infants. ROP screening is a necessary but painful procedure routinely performed in neonatal intensive care units (NICUs), and there remains a lack of consistent and effective pharmacological strategies for managing associated pain, particularly in preterm infants.
Eligible participants will include preterm infants born at or before 32 weeks gestation and scheduled for their first ROP exam. Infants with congenital anomalies, hemodynamic instability, or contraindications to fentanyl will be excluded. Participants will be randomized in a 1:1 ratio to receive either intranasal fentanyl (2 mcg/kg) or an equivalent volume of intranasal saline placebo. Randomization will be stratified by gestational age (\<28 weeks vs. ≥28 weeks) to ensure balance between treatment arms.
The intervention will be administered 5-10 minutes prior to the ROP screening using a mucosal atomization device to optimize nasal absorption and bioavailability. Non-pharmacological comfort measures such as swaddling and non-nutritive sucking will be applied uniformly to all participants as standard of care. The ROP examination will be performed by a pediatric ophthalmologist using a standardized protocol including use of a speculum and scleral depression.
The primary outcome is pain intensity as measured by the Premature Infant Pain Profile-Revised (PIPP-R) at 30 seconds after speculum insertion. Secondary outcomes include additional PIPP-R scores at subsequent timepoints (e.g., speculum removal), changes in physiological parameters (heart rate, oxygen saturation), crying time, pain recovery trajectory, and the occurrence of any adverse events such as respiratory depression, apnea, or need for rescue dosing.
Vital signs and continuous cardiorespiratory monitoring will be conducted before, during, and after the procedure to identify any immediate adverse effects. Pain scoring will be conducted by trained, blinded assessors who are not involved in administering the intervention or performing the ROP exam.
Safety monitoring will include predefined criteria for adverse events and a data safety monitoring plan, including interim review by an independent neonatologist. Any infant experiencing a serious adverse event will be promptly evaluated, and unblinding may occur if necessary for clinical care.
This trial is designed to address a significant gap in neonatal pain management by generating high-quality evidence on the feasibility, safety, and efficacy of intranasal fentanyl in a vulnerable population. The use of a non-invasive, easily administered opioid analgesic could improve procedural pain control without introducing the risks associated with intravenous access. Findings from this study may inform neonatal pain management protocols and support the development of evidence-based guidelines for the use of intranasal fentanyl in NICU settings.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Infants born at <32 weeks gestational age
- Undergoing their first screening for retinopathy of prematurity (ROP)
- Clinically stable at the time of the procedure
- Parental or legal guardian informed consent obtained
- Known or suspected congenital anomalies affecting the nose
- Receipt of systemic analgesics or sedatives at the time of ROP screening
- Nasal obstruction or malformations that interfere with intranasal drug delivery
- Contraindications to fentanyl (e.g., known hypersensitivity)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intranasal Fentanyl Group Fentanyl Citrate (Intranasal) Participants in this group will receive intranasal fentanyl at a dose of 2 mcg/kg administered 5 minutes prior to initiation of retinopathy of prematurity (ROP) screening. Fentanyl will be delivered via a mucosal atomization device in conjunction with standard non-pharmacologic comfort measures. Placebo Group Normal Saline (Placebo, Intranasal) Participants in this group will receive an equivalent volume of intranasal normal saline (placebo) administered 5 minutes prior to ROP screening using a mucosal atomization device. Standard non-pharmacologic comfort measures will also be provided.
- Primary Outcome Measures
Name Time Method Pain intensity during ROP screening 30 seconds after speculum insertion during ROP screening Pain intensity will be measured using the Premature Infant Pain Profile-Revised (PIPP-R) score. The score will be assessed 30 seconds after insertion of the speculum, during the ROP eye examination.
- Secondary Outcome Measures
Name Time Method Proportion of infants with low to mild pain 30 seconds after speculum insertion The proportion of infants experiencing low or mild pain will be assessed using the PIPP-R score, with established thresholds to categorize pain levels. Scores will be assigned by blinded assessors reviewing synchronized video recordings.
Pain response during ROP screening Every 30 seconds throughout the procedure Pain scores will be measured using PIPP-R at 30-second intervals from speculum insertion until the end of the ROP screening to evaluate procedural pain trajectory. Scores will be coded from video by blinded assessors.
Salivary cortisol levels Pre-procedure and 20 minutes post-procedure Salivary cortisol (μg/dL), a hormonal marker of stress, will be measured before the procedure and 20 minutes after to assess endocrine pain response.
Duration of ROP examination Entire ROP procedure from speculum insertion to removal Total duration of the ROP exam will be recorded in seconds from speculum insertion to removal using timestamped video to assess procedural efficiency.
Physiological pain indicators (Heart rate) Baseline, 30 seconds after speculum insertion, 1-minute and 5-minutes post-procedure Changes in heart rate (beats per minute) will be measured as physiological correlates of pain. Data will be collected before, during, and after the procedure.
Pain recovery following ROP screening End of procedure, 1-minute and 5-minutes post-procedure PIPP-R scores will be used to evaluate pain recovery immediately at procedure end, and at 1- and 5-minutes post-procedure. This will assess the time course of pain resolution.
Cry time during and after procedure During and after the ROP screening procedure Total cry time and first cry duration (in seconds) will be measured from video recordings of the procedure, assessed by trained, blinded coders.
Adverse events related to intervention During procedure and up to 4 hours post-intervention Safety will be evaluated by monitoring predefined adverse events such as apnea, bradycardia, hypotension, chest rigidity, desaturation, feeding intolerance, need for airway support, and inadequate pupil dilation.
Physiological pain indicators (RR) Baseline, 30 seconds after speculum insertion, 1-minute and 5-minutes post-procedure Changes in respiratory rate (breaths per minute) will be measured as physiological correlates of pain. Data will be collected before, during, and after the procedure.
Physiological pain indicators (blood pressure) Baseline, 30 seconds after speculum insertion, 1-minute and 5-minutes post-procedure Changes in blood pressure (mmHg) will be measured as physiological correlates of pain. Data will be collected before, during, and after the procedure.
Physiological pain indicators (Oxygen saturation) Baseline, 30 seconds after speculum insertion, 1-minute and 5-minutes post-procedure Changes in oxygen saturation (SpO₂) will be measured as physiological correlates of pain. Data will be collected before, during, and after the procedure.