Use of Intranasal Midazolam to Reduce Stress and Procedural Pain in Premature Infants During Routine ROP Examination.

NCT ID: NCT06889376

Last Updated: 2025-03-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-24

Study Completion Date

2025-07-06

Brief Summary

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The goal of this study is to learn about the safety and effectiveness of intranasal midazolam in newborns and infants born prematurely, undergoing Retinopathy of Prematurity (ROP) screening.

The main question it aims to answer is:

• Does use of intranasal midazolam is a safe, quick, non-invasive medication, that reduces the pain, stress, discomfort, and other complications in patients undergoing ROP screening?

Researchers will compare the intervention group with a comparison group of the patients who will receive routine comfort care.

Detailed Description

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The aim of this parallel, prospective, nonblinded randomised control trial is to assess the effectiveness and safety of intranasal midazolam administered before ROP screening using the DART™ intranasal atomization device in preterm newborns and infants.

Participants: Preterm newborns and infants eligible for routine ROP screening. Recruitment: Parental/legal guardian consent required before random assignment to either the study or control group.

Study Groups and Randomization:

Random Assignment: Block randomization will be used. • Sample Size: 40 newborns/infants (20 in control, 20 in study group).

Study intervention and monitoring:

• Study Group (midazolam group) Intervention: intranasal midazolam (0.2 mg/kg) administered 10 minutes before ROP screening via the DART™ intranasal atomization device.

Comfort Measures:

* 1 ml of 20% glucose solution orally with a pacifier, 5 minutes before screening.
* Swaddling and placement under the radiant warmer.

Monitoring:

* Vital signs: heart rate, respiratory rate, blood pressure, oxygen saturation recorded 10 minutes before screening until 2 hours post-examination.
* Pain assessment (PIPP scale) conducted before, during, and 10, 30 minutes 1 hour and 2 hours post-procedure.
* Modified N-PASS scale to assess the level of sedation conducted before, during, 10, 30 minutes 1 hour and 2 hours post-procedure.

Control Group (non-midazolam group)

* No midazolam administered.
* Comfort measures: 1 ml of 20% glucose solution orally with a pacifier 5 minutes before screening. Swaddling and placement under the radiant warmer.

Monitoring:

* Vital signs: heart rate, respiratory rate, blood pressure, oxygen saturation recorded 10 minutes before screening until 2 hours post-examination.
* Pain assessment (PIPP scale) conducted before, during, and 10, 30 minutes 1 hour and 2 hours post-procedure.

In both groups, observations for:

* Respiratory Distress (apnoea, desaturation, increased work of breathing)
* Cardiovascular Instability (Bradycardia, tachycardia, hypotension)
* Neurological Symptoms (Lethargy, seizures, abnormal tone)
* Gastrointestinal Issues (Feeding intolerance, NEC-like symptoms)
* Infections \& Sepsis (Confirmed or suspected based on clinical signs)

Study Outcome Assessment:

Change in pain and stress symptoms during ROP screening, measured by the Premature Infant Pain Profile (PIPP).

Clinical safety of intranasal midazolam using a nasal atomizer (DART™ intranasal atomization device) in newborns/infants.

Assessment of sedation post intranasal midazolam administration.

Conditions

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Drug Safety

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Intranasal midazolam and comfort care

The newborn/infant qualified for the ROP screening will receive intranasal midazolam before the procedure using a nasal atomizer.

The newborn/infant will also receive comfort care

Group Type EXPERIMENTAL

Intranasal midazolam administration via the DART™ intranasal atomization device along with routine comfort care.

Intervention Type DRUG

Intervention: Intranasal midazolam (0.2 mg/kg) administered 10 minutes before ROP screening via the DART™ intranasal atomization device.

Comfort Measures:

* 1 ml of 20% glucose solution orally with a pacifier, 5 min before screening.
* Swaddling and placement under the radiant warmer.

Monitoring:

* Vital Signs (heart rate, respiratory rate, blood pressure, oxygen saturation monitoring before drug administration until 2 hours after).
* Pain assessment (PIPP scale) conducted before, during, and 10 and 30 min post-procedure.
* Modified N-PASS to assess the level of sedation conducted before, during, 10, 30 minutes 1 hour and 2 hours post-procedure

Observations for signs of:

* Respiratory Distress (apnoea, desaturation, increased work of breathing)
* Cardiovascular Instability (Bradycardia, tachycardia, hypotension)
* Neurological Symptoms (Lethargy, seizures, abnormal tone)
* Gastrointestinal Issues (Feeding intolerance, NEC-like symptoms)

Control group

Control Group (non-midazolam group)

* No midazolam administered.
* Routine comfort care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Intranasal midazolam administration via the DART™ intranasal atomization device along with routine comfort care.

Intervention: Intranasal midazolam (0.2 mg/kg) administered 10 minutes before ROP screening via the DART™ intranasal atomization device.

Comfort Measures:

* 1 ml of 20% glucose solution orally with a pacifier, 5 min before screening.
* Swaddling and placement under the radiant warmer.

Monitoring:

* Vital Signs (heart rate, respiratory rate, blood pressure, oxygen saturation monitoring before drug administration until 2 hours after).
* Pain assessment (PIPP scale) conducted before, during, and 10 and 30 min post-procedure.
* Modified N-PASS to assess the level of sedation conducted before, during, 10, 30 minutes 1 hour and 2 hours post-procedure

Observations for signs of:

* Respiratory Distress (apnoea, desaturation, increased work of breathing)
* Cardiovascular Instability (Bradycardia, tachycardia, hypotension)
* Neurological Symptoms (Lethargy, seizures, abnormal tone)
* Gastrointestinal Issues (Feeding intolerance, NEC-like symptoms)

Intervention Type DRUG

Other Intervention Names

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nasal midazolam

Eligibility Criteria

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Inclusion Criteria

* Newborns qualified for ophthalmologic screening examination to detect retinopathy of prematurity (ROP):

a. Newborns/infants born before the 32 weeks of gestation and/or with a birth weight \<1500 g.
* Obtaining informed consent from a parent/legal guardian.

Exclusion Criteria

* Newborns/infants not qualified for screening ophthalmologic examination (ROP).
* Newborns/infants clinically unstable, with respiratory disorders/cardiovascular instability before the ophthalmologic examination.
* Newborns/infants with congenital developmental defects.
* Newborns/infants receiving analgesic/sedative medications for other reasons.
Maximum Eligible Age

30 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Polish Mother Memorial Hospital Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Agnieszka Nowacka

Principal Investigator, Senior Assistant at Neonatology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ewa Gulczyńska, Professor

Role: STUDY_CHAIR

Polish Mother's Health Center Institute

Locations

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Polish Mother's Health Center Institute Rzgowska 281/289, 93-338 Lodz

Lodz, , Poland

Site Status

Countries

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Poland

Central Contacts

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Agnieszka Nowacka, MSc

Role: CONTACT

+48 607603226

Facility Contacts

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Agnieszka Nowacka, Lek. med.

Role: primary

+48607603226

References

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Salaets T, Lacaze-Masmonteil T, Hokuto I, Gauldin C, Taha A, Smits A, Thewissen L, Van Horebeek I, Shoraisham A, Mohammad K, Suzuki M, Komachi S, Michels K, Turner MA, Allegaert K, Lewis T. Prospective assessment of inter-rater reliability of a neonatal adverse event severity scale. Front Pharmacol. 2023 Sep 7;14:1237982. doi: 10.3389/fphar.2023.1237982. eCollection 2023.

Reference Type BACKGROUND
PMID: 37745081 (View on PubMed)

Salaets T, Turner MA, Short M, Ward RM, Hokuto I, Ariagno RL, Klein A, Beauman S, Wade K, Thomson M, Roberts E, Harrison J, Quinn T, Baer G, Davis J, Allegaert K; International Neonatal Consortium. Development of a neonatal adverse event severity scale through a Delphi consensus approach. Arch Dis Child. 2019 Dec;104(12):1167-1173. doi: 10.1136/archdischild-2019-317399. Epub 2019 Sep 19.

Reference Type BACKGROUND
PMID: 31537552 (View on PubMed)

Morgan ME, Kukora S, Nemshak M, Shuman CJ. Neonatal Pain, Agitation, and Sedation Scale's use, reliability, and validity: a systematic review. J Perinatol. 2020 Dec;40(12):1753-1763. doi: 10.1038/s41372-020-00840-7. Epub 2020 Oct 2.

Reference Type BACKGROUND
PMID: 33009491 (View on PubMed)

Vinall J, Miller SP, Chau V, Brummelte S, Synnes AR, Grunau RE. Neonatal pain in relation to postnatal growth in infants born very preterm. Pain. 2012 Jul;153(7):1374-1381. doi: 10.1016/j.pain.2012.02.007.

Reference Type BACKGROUND
PMID: 22704600 (View on PubMed)

COMMITTEE ON FETUS AND NEWBORN and SECTION ON ANESTHESIOLOGY AND PAIN MEDICINE. Prevention and Management of Procedural Pain in the Neonate: An Update. Pediatrics. 2016 Feb;137(2):e20154271. doi: 10.1542/peds.2015-4271. Epub 2016 Jan 25.

Reference Type BACKGROUND
PMID: 26810788 (View on PubMed)

Snyers D, Tribolet S, Rigo V. Intranasal Analgosedation for Infants in the Neonatal Intensive Care Unit: A Systematic Review. Neonatology. 2022;119(3):273-284. doi: 10.1159/000521949. Epub 2022 Mar 1.

Reference Type BACKGROUND
PMID: 35231912 (View on PubMed)

Pasero C. Pain assessment in infants and young children: Premature Infant Pain Profile. Am J Nurs. 2002 Sep;102(9):105-6. doi: 10.1097/00000446-200209000-00065. No abstract available.

Reference Type BACKGROUND
PMID: 12394025 (View on PubMed)

Francis K. What Is Best Practice for Providing Pain Relief During Retinopathy of Prematurity Eye Examinations? Adv Neonatal Care. 2016 Jun;16(3):220-8. doi: 10.1097/ANC.0000000000000267.

Reference Type BACKGROUND
PMID: 27195471 (View on PubMed)

Ballantyne M, Stevens B, McAllister M, Dionne K, Jack A. Validation of the premature infant pain profile in the clinical setting. Clin J Pain. 1999 Dec;15(4):297-303. doi: 10.1097/00002508-199912000-00006.

Reference Type BACKGROUND
PMID: 10617258 (View on PubMed)

Brummelte S, Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, Gover A, Synnes AR, Miller SP. Procedural pain and brain development in premature newborns. Ann Neurol. 2012 Mar;71(3):385-96. doi: 10.1002/ana.22267. Epub 2012 Feb 28.

Reference Type BACKGROUND
PMID: 22374882 (View on PubMed)

Mitchell AJ, Green A, Jeffs DA, Roberson PK. Physiologic effects of retinopathy of prematurity screening examinations. Adv Neonatal Care. 2011 Aug;11(4):291-7. doi: 10.1097/ANC.0b013e318225a332.

Reference Type BACKGROUND
PMID: 22123352 (View on PubMed)

Moral-Pumarega MT, Caserio-Carbonero S, De-La-Cruz-Bertolo J, Tejada-Palacios P, Lora-Pablos D, Pallas-Alonso CR. Pain and stress assessment after retinopathy of prematurity screening examination: indirect ophthalmoscopy versus digital retinal imaging. BMC Pediatr. 2012 Aug 28;12:132. doi: 10.1186/1471-2431-12-132.

Reference Type BACKGROUND
PMID: 22928523 (View on PubMed)

Thirunavukarasu AJ, Hassan R, Savant SV, Hamilton DL. Analgesia for retinopathy of prematurity screening: A systematic review. Pain Pract. 2022 Sep;22(7):642-651. doi: 10.1111/papr.13138. Epub 2022 Jun 27.

Reference Type BACKGROUND
PMID: 35703418 (View on PubMed)

Slevin M, Murphy JF, Daly L, O'Keefe M. Retinopathy of prematurity screening, stress related responses, the role of nesting. Br J Ophthalmol. 1997 Sep;81(9):762-4. doi: 10.1136/bjo.81.9.762.

Reference Type BACKGROUND
PMID: 9422929 (View on PubMed)

Other Identifiers

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98/2024

Identifier Type: -

Identifier Source: org_study_id

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