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

NCT06889376 | Not Yet Recruiting Phase 1

• 1 other identifier: 98/2024
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Safety

Keywords

intranasal midazolam; ROP screening; Premature infants

Outcome Measures

Primary Outcomes (1)

• Pain assessment pre and post intranasal midazolam administration

  Primary Endpoint: \- Change in the occurrence of pain symptoms and stress associated with screening ophthalmologic examination (ROP). Use of Premature Infant Pain Profile (PIPP) score * Purpose: To evaluate pain and stress responses before, during, and after the procedure. * Scoring Components: * Heart rate changes. * Oxygen saturation levels. * Facial expressions (brow bulge, eye squeeze, nasolabial furrow). * Behavioural state (awake, fussy, crying). * Gestational age adjustment.

  PIPP Score Assessment Time Points: 5 minutes before drug administration, during drug administration, 10, 30 minutes 1 hour and 2 hours post-procedure

Secondary Outcomes (2)

• Evaluation of clinical safety of intranasal midazolam using a nasal atomizer (DART™ intranasal atomisation device) in newborns/infants.

  Neonatal Adverse Event Severity Scale (NAESS) will be reported up to 24 hours following drug administration.

• Sedation assessment after intranasal midazolam administration.

  Modified N-PASS score used to assess level of sedation time points: 5 minutes before drug administration, during drug administration, 10, 30 minutess, 1 hour and 2 hours post - drug administration.

Study Arms (2)

Intranasal midazolam and comfort care

EXPERIMENTAL

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

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

Control group

NO INTERVENTION

Control Group (non-midazolam group) * No midazolam administered. * Routine comfort care

Interventions

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

Also known as: nasal midazolam

Intranasal midazolam and comfort care

Eligibility Criteria

• Age: Up to 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Polish Mother Memorial Hospital Research Institute: lead

Study Sites (1)

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

Lodz, 93-338, Poland

Location

Related Publications (14)

• 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.

  PMID: 37745081 BACKGROUND

• 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.

  PMID: 31537552 BACKGROUND

• 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.

  PMID: 33009491 BACKGROUND

• 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.

  PMID: 22704600 BACKGROUND

• 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.

  PMID: 26810788 BACKGROUND

• 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.

  PMID: 35231912 BACKGROUND

• 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.

  PMID: 12394025 BACKGROUND

• 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.

  PMID: 27195471 BACKGROUND

• 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.

  PMID: 10617258 BACKGROUND

• 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.

  PMID: 22374882 BACKGROUND

• 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.

  PMID: 22123352 BACKGROUND

• 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.

  PMID: 22928523 BACKGROUND

• 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.

  PMID: 35703418 BACKGROUND

• 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.

  PMID: 9422929 BACKGROUND

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Ewa Gulczyńska, Professor

  Polish Mother's Health Center Institute

  STUDY CHAIR

Central Study Contacts

Agnieszka Nowacka, MSc

CONTACT

+48 607603226; agn.nowacka@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Senior Assistant at Neonatology Department

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: March 21, 2025
• Study Start: March 24, 2025
• Primary Completion: June 1, 2025
• Study Completion: July 6, 2025
• Last Updated: March 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)