Neonatal PainPhase 1/2FIREFLYNCT07112430
Fentanyl Intranasal for Retinopathy of Prematurity Screening in Preterm Infants
A Phase 1/2 study testing Fentanyl Citrate (Intranasal) in people with Neonatal Pain and Retinopathy of Prematurity (ROP), run by Marsha Campbell-Yeo at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neonatal Pain, Retinopathy of Prematurity (ROP), Pain Management
- What is being tested?
- Fentanyl Citrate (Intranasal)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteCanada
- Study dates
- 9 Sep 2026to 1 Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
IWK Health
Halifax, Nova Scotia
Helen McCord, 9024971412, mccordhelen@hotmail.com
About this study
Official title: Intranasal Fentanyl to Reduce Pain Intensity Associated With Retinopathy of Prematurity Screening in Preterm Infants: A Randomized Control Trial
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.
Read the 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.
- Conditions
- Neonatal Pain, Retinopathy of Prematurity (ROP), Pain Management, Infant, Premature, Fentanyl, Infant, Newborn
- Being tested
- Fentanyl Citrate (Intranasal), Normal Saline (Placebo, Intranasal)
- 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
- Medical subject headings
- Retinopathy of Prematurity, Agnosia, Premature Birth, Pain, Procedural
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fentanyl Citrate (Intranasal)Drug
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.
Normal Saline (Placebo, Intranasal)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intranasal Fentanyl Group | Experimental | Participants in this group will receive intranasal fentanyl at a dose of 2 mcg/kg administered 10 minutes prior to initiation of retinopathy of prematurity (ROP) screening. The study drug will be delivered via a mucosal atomization device 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. Receives: Drug: Fentanyl Citrate (Intranasal) |
| Placebo Group | Placebo comparator | Participants in this group will receive an equivalent volume of intranasal 0.9% normal saline placebo administered 10 minutes prior to initiation of retinopathy of prematurity (ROP) screening using a mucosal atomization device. 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. Receives: Drug: Normal Saline (Placebo, Intranasal) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity 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.
Measured: First 30 seconds after speculum insertion during ROP screening
Secondary outcomes (8)
Proportion of infants with low to mild pain
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.
Measured: During procedure and at 1- and 5-minutes post-procedure
Ongoing pain response during ROP screening
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.
Measured: Every 30 seconds during the procedure
Pain recovery following ROP screening
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.
Measured: 1-minute and 5-minutes post-procedure
Cry duration
Total cry duration (in seconds) will be measured from synchronized video recordings during the ROP examination and recovery period by trained, blinded assessors.
Measured: From speculum insertion through 5 minutes post-procedure
Salivary cortisol response
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.
Measured: 20 minutes pre-procedure and 20 minutes post-procedure
Adverse events
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.
Measured: During the procedure and up to 4 hours post-intervention
Duration of ROP examination
Total duration of the ROP examination will be measured in seconds from speculum insertion to removal using timestamped video recordings.
Measured: During the procedure
Physiological responses
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.
Measured: Baseline, during the procedure, and at 1- and 5-minutes post-procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2025
- Study start9 Sep 2026 (estimated)
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neonatal PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marsha Campbell-Yeo
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Dalhousie University, IWK Health Centre
- Responsible party
- Sponsor-investigator, Marsha Campbell-Yeo, IWK Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07112430
- Sponsor's protocol ID
- IWK_INF_PainTrial2025
- Acronym
- FIREFLY
- Status last verified
- Jun 2025
- First submitted
- 29 Jul 2025
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The plan to share individual participant data (IPD) is currently undecided. IPD sharing may be considered in the future depending on institutional policies, ethics approval, and participant consent. If data sharing is pursued, it will involve de-identified data underlying published results, and appropriate data use agreements and secure access mechanisms will be established. No final decision has been made at this stage.
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.
PubMed 42458331
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Fentanyl to Reduce Pain Intensity Associated With Retinopathy of Prematurity Screening in Preterm Infants: A Randomized Control Trial
- ClinicalTrials.gov ID
- NCT07112430
- Acronym / sponsor ID
- FIREFLY / IWK_INF_PainTrial2025
- Conditions
- Neonatal Pain, Retinopathy of Prematurity (ROP), Pain Management, Infant, Premature, Fentanyl, Infant, Newborn
- Keywords
- intranasal fentanyl, fentanyl, neonatal analgesia, procedural pain, ROP screening, Retinopathy of Prematurity, Preterm infants, Premature infants
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Marsha Campbell-YeoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Dalhousie University, IWK Health Centre
- Study start
- 9 Sep 2026 (estimated)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 8 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Intranasal Fentanyl Group | Experimental | Drug: Fentanyl Citrate (Intranasal)Participants in this group will receive intranasal fentanyl at a dose of 2 mcg/kg administered 10 minutes prior to initiation of retinopathy of prematurity (ROP) screening. The study drug will be delivered via a mucosal atomization device 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. |
| Placebo Group | Placebo comparator | Drug: Normal Saline (Placebo, Intranasal)Participants in this group will receive an equivalent volume of intranasal 0.9% normal saline placebo administered 10 minutes prior to initiation of retinopathy of prematurity (ROP) screening using a mucosal atomization device. 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Intranasal Fentanyl Group |
| 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. | Drug | Placebo Group |
Primary outcome
Pain intensity during ROP screening
Time frame: 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.
8 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
- Derived from this study: PubMed 42458331McCord 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.
- Individual participant dataSharing planned: Undecided. The plan to share individual participant data (IPD) is currently undecided. IPD sharing may be considered in the future depending on institutional policies, ethics approval, and participant consent. If data sharing is pursued, it will involve de-identified data underlying published results, and appropriate data use agreements and secure access mechanisms will be established. No final decision has been made at this stage.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fentanyl Citrate (Intranasal) in people with Neonatal Pain and Retinopathy of Prematurity (ROP), run by Marsha Campbell-Yeo at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Helen McCord, BScN, MN, PhD Candidate, NNP (19024971412, mccordhelen@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain intensity during ROP screening (time frame: First 30 seconds after speculum insertion during ROP screening). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07112430, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.