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

Phase 1

Not yet recruiting

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

• Registration Number: NCT06889376
• Lead Sponsor: Polish Mother Memorial Hospital Research Institute

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.

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 Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-03-16
• Last Update Submitted: 2025-03-16
• Study First Posted: 2025-03-21
• Last Update Posted: 2025-03-21
• Study Start: 2025-03-24
• Primary Completion: 2025-06-01
• Study Completion: 2025-07-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intranasal midazolam and comfort care	Intranasal midazolam administration via the DART™ intranasal atomization device along with routine 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

Primary Outcome Measures

Name	Time	Method
Pain assessment pre and post intranasal midazolam administration	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.

Secondary Outcome Measures

Name	Time	Method
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.	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.
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.	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

Trial Locations

Locations (1)

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