Intranasal Hydromorphone for the Treatment of Acute Pain in Children: A Pilot Study.

Intranasal hydromorphone has been shown to be effective in reducing acute pain in adults. It has not been previously studied in children, but may be a viable option for effectively and safely reducing pain in children by administering an analgesic by the intranasal route.

This study will be a prospective, open-label pilot study of intranasal hydromorphone in children with moderate to severe acute pain presenting to the pediatric emergency department. The investigators aim to describe the amount of pain reduction associated with intranasal hydromorphone, and to determine the optimal dose of intranasal hydromorphone associated with a clinically meaningful improvement in acute pain.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Hydromorphone

Detailed Description

Primary Aim: Determine the change in pain intensity in children with moderate to severe pain who receive intranasal hydromorphone one hour after administration.

Secondary Aim(s): Describe the incidence of minor and major adverse events associated with intranasal hydromorphone in children with acute pain.

The investigators will assess the patient's pain at baseline (prior to study drug administration), then after study drug administration: 5 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and then every 30 minutes thereafter until 6 hours; administration of non-protocolized rescue medication administration (i.e. administered after first two rescue doses of IN hydromorphone); or discharge from emergency department (whichever comes first). The pain score at 60 minutes will be the primary outcome.

The investigators will evaluate qualitative improvement in pain intensity at 15- and 30-minutes after study drug administration. If there is no improvement, or worsening of pain intensity, at each assessment, an additional rescue dose rescue dose of intranasal hydromorphone will be administered. After 60 minutes, the treating physician may administer any additional rescue medications at their discretion to treat the child's pain.

The patient will be assessed for minor and major adverse events for the duration of the study.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 4 to 17 years old, inclusive
• Moderate to severe pain (i.e. FPS-R or vNRS score of 4 or more)
• Requires parenteral opioid analgesic to treat their pain, as decided by treating physician

Exclusion Criteria:

• Allergy or known contraindication to receiving opioids
• Receipt of any opioid or benzodiazepine within preceding 6 hours
• Presence of intranasal obstruction that cannot be cleared readily
• Cannot speak English or Spanish
• Patient unlikely to be able to complete self-report measures of pain or questionnaires
• Known liver or kidney problems
• Currently critically ill
• Chronic pain condition (e.g. sickle cell disease, fibromyalgia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal hydromorphone; Hydromorphone, intranasal. 2 mg/mL concentration. Initial dose: 0.03 mg/kg, maximum single dose 4 mg. Rescue dose: 0.015 mg/kg, maximum single dose 2 mg.	Drug: Hydromorphone; To be administered by intranasal route using mucosal atomization device.; Other Names: Dilaudid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on Faces Pain Scale - Revised	Pain was measured using the Faces Pain Scale - Revised (FPS-R). The FPS-R is a self-reported measure of pain that is administered using a picture of 6 different faces lined up in a row, each face representing an escalating degree of pain intensity. The faces, starting from the left-most face and moving towards the right-most face, are scored 0, 2, 4, 6, 8 and 10. A score of 0 represents no pain, a score of 10 represents "very much pain" (i.e. maximum possible pain). More information about the FPS-R can be found here: https://bit.ly/2VPk8GM	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Minor Adverse Events	Lightheadedness, dizziness; confusion; sleepy, drowsy, tiredness; nausea; vomiting; itchiness, warm sensation; dry mouth; bad taste in mouth; rhinitis.	6 hours
Number of Major Adverse Events	Oxygen desaturation, respiratory depression, hypotension, bradycardia, need for supplemental oxygen, bag-mask ventilation, airway support intervention, administration naloxone.	6 hours
Score on Verbal Numeric Rating Scale	Pain was measured using the Verbal Numerical Rating Scale (VNRS). The VNRS is a self-reported measure of pain that is administered verbally by asking a patient to rate their pain on a scale from 0 to 10, with 0 representing no pain, and 10 representing maximum pain. More information about the VNRS in children can be found here: https://bit.ly/2VZ7aWU	1 hour

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Daniel Tsze, MD, MPH, Columbia University

Publications and helpful links

General Publications

• Tsze DS, Pan SS, DePeter KC, Wagh AM, Gordon SL, Dayan PS. Intranasal hydromorphone for treatment of acute pain in children: A pilot study. Am J Emerg Med. 2019 Jun;37(6):1128-1132. doi: 10.1016/j.ajem.2019.03.013. Epub 2019 Mar 13.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: May 5, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (Estimate): May 7, 2015

Study Record Updates

• Last Update Posted (Actual): May 28, 2019
• Last Update Submitted That Met QC Criteria: May 7, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Pediatric; Intranasal; Emergency department; Hydromorphone
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: AAAP5709