Intranasal Dexmedetomidine for Pain Management During Screening for Retinopathy of Prematurity

NCT06067958 | Recruiting Phase 3

• 1 other identifier: 0096-23-ASF
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Preterm infants undergo serial eye examinations during their hospital stay to monitor for the development of a specific disease termed "retinopathy of prematurity". While those examinations are known to cause significant pain and stress, the current standard of care (sucrose and local anesthesia) is not adequate in terms of alleviation of pain. Purpose: The goal of this clinical trial is to test the effectiveness of dexmedetomidine for pain management in preterm infants undergoing routine eye examinations. The main questions it aims to answer are:

• Does dexmedetomidine reduce the pain scores of preterm infants during and shortly after eye assessments in comparison to placebo (saline 0.9%).
• Does dexmedetomidine cause more adverse effects than placebo. In this crossover study participants will receive either dexmedetomidine or saline 0.9% intranasally 30 minutes before the examination, on top of the current standard of care. The participants will be monitored closely for 5 hours to note differences in adverse effects. The researchers will use video monitoring to assess the pain scores using a standardized and validated scoring system.

Conditions

Retinopathy of Prematurity; Dexmedetomidine

Keywords

Retinopathy of Prematurity; Dexmedetomidine; Pain; Analgesia; Premature Infant Pain Profile - Revised

Outcome Measures

Primary Outcomes (1)

• The Premature Infant Pain Profile: Revised, at peak

  The Premature Infant Pain Profile: Revised (PIPP-R) is a scoring system for pain and discomfort in preterm infants. The maximum attainable PIPP-R score is 21 for preterm infants \<28 weeks GA and 18 for full-term infants. The higher the score, the greater the discomfort. Every participant will be assessed using video recordings which will start 5 minutes before the administration of oral sucrose 24% and will continue until 5 minutes after the removal of the eyelid retractor. The primary outcome will be the PIPP-R score one minute after the insertion of the retractor.

  PIPP-R score will be assessed 60 seconds after the insertion of the retractor

Secondary Outcomes (7)

• The Premature Infant Pain Profile: Revised, 5 minutes

  5 minutes after the insertion of the retractor

• The Premature Infant Pain Profile: Revised, at completion

  2 minutes after the removal the retractors

• Apnea

  From time 0 until 5 hours after the examination

• Bradycardia

  From time 0 until 5 hours after the examination

• Heart rate

  Assessed every hour from time 0 until 5 hours after the examination

Study Arms (2)

Dexmedetomidine

ACTIVE COMPARATOR

Intranasal Dexmedetomidine 2 microgram/kilogram, 30 minutes before eye examination

Drug: Dexmedetomidine

Placebo

PLACEBO COMPARATOR

Saline 0.9%, volume will change to match that of dexmedetomidine based on participants' weight. 30 minutes before eye examination

Drug: Saline

Interventions

Dexmedetomidine DRUG

Intranasal administration of dexmedetomidine will be done using MAD Nasal atomization device (Teleflex Medical, 3015 Carrington Mill Blvd, Morrisville, NC 27560, USA). Administration will be given to both nares at a similar volume.

Dexmedetomidine

Saline DRUG

Intranasal administration of saline 0.9% will be done using MAD Nasal atomization device (Teleflex Medical, 3015 Carrington Mill Blvd, Morrisville, NC 27560, USA). Administration will be given to both nares at a similar volume.

Placebo

Eligibility Criteria

• Age: 4 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gestational age \< 31 weeks post-menstrual age, or birth weight \< 1500 grams
• Informed consent signed by one of the parents

You may not qualify if:

• Invasive ventilation at the time of the eye assessment
• Multiple congenital anomalies
• Chromosomal / genetic anomalies
• Infant received a sedative drug in last 5 days
• Eye examination for reasons other than retinopathy of prematurity screening
• Attending physician deemed the patient not stable enough

Sponsors & Collaborators

• Assaf-Harofeh Medical Center: lead

Study Sites (1)

Assaf-Harofeh Medical Center

Be’er Ya‘aqov, Center, 7033001, Israel

RECRUITING

Related Publications (23)

• Wood EH, Chang EY, Beck K, Hadfield BR, Quinn AR, Harper CA 3rd. 80 Years of vision: preventing blindness from retinopathy of prematurity. J Perinatol. 2021 Jun;41(6):1216-1224. doi: 10.1038/s41372-021-01015-8. Epub 2021 Mar 5.

  PMID: 33674712 BACKGROUND

• Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Paul Chan RV, Berrocal A, Binenbaum G, Blair M, Peter Campbell J, Capone A Jr, Chen Y, Dai S, Ells A, Fleck BW, Good WV, Elizabeth Hartnett M, Holmstrom G, Kusaka S, Kychenthal A, Lepore D, Lorenz B, Martinez-Castellanos MA, Ozdek S, Ademola-Popoola D, Reynolds JD, Shah PK, Shapiro M, Stahl A, Toth C, Vinekar A, Visser L, Wallace DK, Wu WC, Zhao P, Zin A. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021 Oct;128(10):e51-e68. doi: 10.1016/j.ophtha.2021.05.031. Epub 2021 Jul 8.

  PMID: 34247850 BACKGROUND

• Nayak R, Nagaraj KN, Gururaj G. Prevention of Pain During Screening for Retinopathy of Prematurity: A Randomized Control Trial Comparing Breast Milk, 10% Dextrose and Sterile Water. Indian J Pediatr. 2020 May;87(5):353-358. doi: 10.1007/s12098-020-03182-6. Epub 2020 Jan 27.

  PMID: 31989459 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

• Padhi TR, Sareen D, Pradhan L, Jalali S, Sutar S, Das T, Modi RR, Behera UC. Evaluation of retinopathy of prematurity screening in reverse Kangaroo Mother Care: a pilot study. Eye (Lond). 2015 Apr;29(4):505-8. doi: 10.1038/eye.2014.340. Epub 2015 Jan 23.

  PMID: 25613847 BACKGROUND

• Valeri BO, Holsti L, Linhares MB. Neonatal pain and developmental outcomes in children born preterm: a systematic review. Clin J Pain. 2015 Apr;31(4):355-62. doi: 10.1097/AJP.0000000000000114.

  PMID: 24866853 BACKGROUND

• Walker SM. Long-term effects of neonatal pain. Semin Fetal Neonatal Med. 2019 Aug;24(4):101005. doi: 10.1016/j.siny.2019.04.005. Epub 2019 Apr 5.

  PMID: 30987942 BACKGROUND

• Nesargi SV, Nithyanandam S, Rao S, Nimbalkar S, Bhat S. Topical anesthesia or oral dextrose for the relief of pain in screening for retinopathy of prematurity: a randomized controlled double-blinded trial. J Trop Pediatr. 2015 Feb;61(1):20-4. doi: 10.1093/tropej/fmu058. Epub 2014 Nov 5.

  PMID: 25376189 BACKGROUND

• Marsh VA, Young WO, Dunaway KK, Kissling GE, Carlos RQ, Jones SM, Shockley DH, Weaver NL, Ransom JL, Gal P. Efficacy of topical anesthetics to reduce pain in premature infants during eye examinations for retinopathy of prematurity. Ann Pharmacother. 2005 May;39(5):829-33. doi: 10.1345/aph.1E476. Epub 2005 Mar 29.

  PMID: 15797982 BACKGROUND

• Disher T, Cameron C, Mitra S, Cathcart K, Campbell-Yeo M. Pain-Relieving Interventions for Retinopathy of Prematurity: A Meta-analysis. Pediatrics. 2018 Jul;142(1):e20180401. doi: 10.1542/peds.2018-0401. Epub 2018 Jun 1.

  PMID: 29858451 BACKGROUND

• Dempsey E, McCreery K. Local anaesthetic eye drops for prevention of pain in preterm infants undergoing screening for retinopathy of prematurity. Cochrane Database Syst Rev. 2011 Sep 7;2011(9):CD007645. doi: 10.1002/14651858.CD007645.pub2.

  PMID: 21901708 BACKGROUND

• Campbell-Yeo M, Benoit B. Use of morphine before retinopathy of prematurity examinations. Lancet. 2018 Dec 15;392(10164):2521-2523. doi: 10.1016/S0140-6736(18)32324-9. Epub 2018 Nov 30. No abstract available.

  PMID: 30509742 BACKGROUND

• Alselaimy R, Al Tawil L, Abouammoh MA. Anesthesia in retinopathy of prematurity. Saudi J Ophthalmol. 2022 Oct 14;36(3):251-259. doi: 10.4103/sjopt.sjopt_229_21. eCollection 2022 Jul-Sep.

  PMID: 36276254 BACKGROUND

• Hartley C, Moultrie F, Hoskin A, Green G, Monk V, Bell JL, King AR, Buckle M, van der Vaart M, Gursul D, Goksan S, Juszczak E, Norman JE, Rogers R, Patel C, Adams E, Slater R. Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial. Lancet. 2018 Dec 15;392(10164):2595-2605. doi: 10.1016/S0140-6736(18)31813-0. Epub 2018 Nov 30.

  PMID: 30509743 BACKGROUND

• Sindhur M, Balasubramanian H, Srinivasan L, Kabra NS, Agashe P, Doshi A. Intranasal fentanyl for pain management during screening for retinopathy of prematurity in preterm infants: a randomized controlled trial. J Perinatol. 2020 Jun;40(6):881-887. doi: 10.1038/s41372-020-0608-2. Epub 2020 Feb 13.

  PMID: 32054982 BACKGROUND

• McDonald D, Palsgraf H, Shah P. Dexmedetomidine - An emerging option for sedation in neonatal patients. J Perinatol. 2022 Jul;42(7):845-855. doi: 10.1038/s41372-022-01351-3. Epub 2022 Feb 23.

  PMID: 35197548 BACKGROUND

• O'Mara K, Gal P, Wimmer J, Ransom JL, Carlos RQ, Dimaguila MA, Davanzo CC, Smith M. Dexmedetomidine versus standard therapy with fentanyl for sedation in mechanically ventilated premature neonates. J Pediatr Pharmacol Ther. 2012 Jul;17(3):252-62. doi: 10.5863/1551-6776-17.3.252.

  PMID: 23258968 BACKGROUND

• Laudenbach V, Mantz J, Lagercrantz H, Desmonts JM, Evrard P, Gressens P. Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology. 2002 Jan;96(1):134-41. doi: 10.1097/00000542-200201000-00026.

  PMID: 11753013 BACKGROUND

• Lewis J, Bailey CR. Intranasal dexmedetomidine for sedation in children; a review. J Perioper Pract. 2020 Jun;30(6):170-175. doi: 10.1177/1750458919854885. Epub 2019 Jun 27.

  PMID: 31246159 BACKGROUND

• Bua J, Massaro M, Cossovel F, Monasta L, Brovedani P, Cozzi G, Barbi E, Demarini S, Travan L. Intranasal dexmedetomidine, as midazolam-sparing drug, for MRI in preterm neonates. Paediatr Anaesth. 2018 Aug;28(8):747-748. doi: 10.1111/pan.13454. No abstract available.

  PMID: 30144232 BACKGROUND

• Yuen VM, Hui TW, Irwin MG, Yao TJ, Wong GL, Yuen MK. Optimal timing for the administration of intranasal dexmedetomidine for premedication in children. Anaesthesia. 2010 Sep;65(9):922-9. doi: 10.1111/j.1365-2044.2010.06453.x.

  PMID: 20645951 BACKGROUND

• Stevens BJ, Gibbins S, Yamada J, Dionne K, Lee G, Johnston C, Taddio A. The premature infant pain profile-revised (PIPP-R): initial validation and feasibility. Clin J Pain. 2014 Mar;30(3):238-43. doi: 10.1097/AJP.0b013e3182906aed.

  PMID: 24503979 BACKGROUND

• Slater R, Hartley C, Moultrie F, Adams E, Juszczak E, Rogers R, Norman JE, Patel C, Stanbury K, Hoskin A, Green G; Poppi Trial Team. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol. Wellcome Open Res. 2016 Nov 15;1:7. doi: 10.12688/wellcomeopenres.10005.2.

  PMID: 28066825 BACKGROUND

MeSH Terms

Conditions

Retinopathy of Prematurity; Pain; Agnosia

Interventions

Dexmedetomidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Sagee Nissimov, MD

CONTACT

97289779080; sageen@shamir.gov.il

Iris Morag, MD

CONTACT

97289778286; IRISMO@shamir.gov.il

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The units pharmacologist will be responsible for patient assignment and preparation of the medication / placebo syringes but will remain blinded to the other aspects of the trial. The patient's nurse, attending physician, ophthalmologist, investigator and outcome assessor will remain blinded to the patient allocation
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This will be a crossover, prospective randomized controlled trial. Block randomization will be performed before the first eye examination. Every participant will undergo two eye examinations - one following exposure to dexmedetomidine and one following placebo.

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 5, 2023
• Study Start: December 11, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)