Fentanyl Intranasal for Retinopathy of Prematurity Screening in Preterm Infants

NCT ID: NCT07112430

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2027-05-01

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.

Conditions

Neonatal Pain; Retinopathy of Prematurity (ROP); Pain Management; Infant, Premature; Fentanyl; Infant, Newborn; Neonatal Intensive Care Units; Analgesia; Intranasal Drug Administration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intranasal Fentanyl Group

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.

Group Type: EXPERIMENTAL

Fentanyl Citrate (Intranasal)

Intervention Type: DRUG

Fentanyl citrate will be administered intranasally at a dose of 2 mcg/kg via a mucosal atomization device, 5 minutes prior to ROP screening. Used in conjunction with standard non-pharmacologic comfort strategies.

Placebo Group

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.

Group Type: PLACEBO_COMPARATOR

Normal Saline (Placebo, Intranasal)

Intervention Type: DRUG

An equivalent volume of intranasal normal saline will be administered using a mucosal atomization device, 5 minutes prior to ROP screening.

Interventions

Fentanyl Citrate (Intranasal)

Fentanyl citrate will be administered intranasally at a dose of 2 mcg/kg via a mucosal atomization device, 5 minutes prior to ROP screening. Used in conjunction with standard non-pharmacologic comfort strategies.

Intervention Type: DRUG

Normal Saline (Placebo, Intranasal)

An equivalent volume of intranasal normal saline will be administered using a mucosal atomization device, 5 minutes prior to ROP screening.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 30 Weeks
• Maximum Eligible Age: 36 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

IWK Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Helen McCord, BScN, MN, PhD Candidate, NNP

Role: CONTACT

mccordhelen@hotmail.com

19024971412

Other Identifiers

IWK_INF_PainTrial2025

Identifier Type: -

Identifier Source: org_study_id