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

March 16, 2025 updated by: Agnieszka Nowacka, Polish Mother Memorial Hospital Research Institute

The Use of Intranasal Sedation with Midazolam to Reduce Stress, Discomfort and Procedural Pain in Preterm Newborns and Infants During Routine ROP Screening

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Poland
      • Lodz, Poland, 93-338
        • Polish Mother's Health Center Institute Rzgowska 281/289, 93-338 Lodz
        • Contact:
        • Contact:
          • Agnieszka Nowacka, Lek. med

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: 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)
Other Names:
  • nasal midazolam
No Intervention: Control group

Control Group (non-midazolam group)

  • No midazolam administered.
  • Routine comfort care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain assessment pre and post intranasal midazolam administration
Time Frame: PIPP Score Assessment Time Points: 5 minutes before drug administration, during drug administration, 10, 30 minutes 1 hour and 2 hours post-procedure

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of clinical safety of intranasal midazolam using a nasal atomizer (DART™ intranasal atomisation device) in newborns/infants.
Time Frame: Neonatal Adverse Event Severity Scale (NAESS) will be reported up to 24 hours following drug administration.

To accurately report the adverse events during intranasal midazolam administration using a nasal atomizer (DART™ intranasal atomisation device) in newborns/infants, the Neonatal Adverse Event Severity Scale (NAESS) will be used.

This scale contains generic severity criteria that can occur in neonates, followed by a list of 35 specific medical conditions: neurological, cardiovascular, respiratory, gastrointestinal, infectious, general and any other symptoms

Each of the criteria is divided into grading system:

Grade 1 - Mild Grade 2 - Moderate Grade 3 - Severe Grade 4 - Life- threatening Grade 5 - Death Assessment of the severity of the adverse event is based on the observation of the changes in the following components: age appropriate behavioural changes, changes from the baseline in the vital signs, changes in the required care and monitoring. Only changes from the baseline condition will be considered as a reported adverse-events.
Neonatal Adverse Event Severity Scale (NAESS) will be reported up to 24 hours following drug administration.
Sedation assessment after intranasal midazolam administration.
Time Frame: 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.

To assess the sedation status after intranasal midazolam administration, Modified N-PASS: Neonatal Sedation Assessment Scale will be used.

The assessment criteria of the scale include:

  • Crying/ Irritability
  • Behaviour State
  • Facial Expression
  • Extremities Tone
  • Vital Signs: HR, RR, BP, SaO2 Each of the criteria scores from 0 to -2, the sum provides a total score and note as a negative score (0 to -10).

Deep sedation: -10 to -6 Light sedation: -5 to - 2 Normal: -1 to +3
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Polish Mother Memorial Hospital Research Institute

Investigators

  • Study Chair: Ewa Gulczyńska, Professor, Polish Mother's Health Center Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 24, 2025

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

July 6, 2025

Study Registration Dates

First Submitted

February 19, 2025

First Submitted That Met QC Criteria

March 16, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 16, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98/2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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