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

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02437669
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Actual Duration (Months): 35
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Hydromorphone	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intranasal Hydromorphone for the Treatment of Acute Pain in Children: A Pilot Study.
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Score on Faces Pain Scale - Revised [1 hour]

   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

Secondary Outcome Measures

1. Number of Minor Adverse Events [6 hours]

   Lightheadedness, dizziness; confusion; sleepy, drowsy, tiredness; nausea; vomiting; itchiness, warm sensation; dry mouth; bad taste in mouth; rhinitis.

2. Number of Major Adverse Events [6 hours]

   Oxygen desaturation, respiratory depression, hypotension, bradycardia, need for supplemental oxygen, bag-mask ventilation, airway support intervention, administration naloxone.

3. Score on Verbal Numeric Rating Scale [1 hour]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Morgan Stanley Children's Hospital	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 16, 2018

More Information

Publications

None provided.

• Responsible Party: Daniel S Tsze, MD, MPH, Assistant Professor of Pediatrics at CUMC, Columbia University
• ClinicalTrials.gov Identifier: NCT02437669
• Other Study ID Numbers: AAAP5709
• First Posted: May 7, 2015
• Last Update Posted: May 28, 2019
• Last Verified: May 1, 2019

• Keywords provided by Daniel S Tsze, MD, MPH, Assistant Professor of Pediatrics at CUMC, Columbia University: Intranasal; Hydromorphone; Pediatric; Emergency department
• Additional relevant MeSH terms: Acute Pain; Hydromorphone

Study Results

Participant Flow

Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	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. Hydromorphone: To be administered by intranasal route using mucosal atomization device.
Period Title: Overall Study
STARTED	35
COMPLETED	35
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	Children who received intranasal hydromorphone
Overall Participants	35
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	11
Sex: Female, Male (Count of Participants)
Female	13 37.1%
Male	22 62.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	26 74.3%
White	5 14.3%
Black	3 8.6%
More than one race	1 2.9%
Baseline pain score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7 (0.4)

Outcome Measures

1. Primary Outcome

Title	Score on Faces Pain Scale - Revised
Description	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
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Decrease in pain score one hour after terminal dose of intranasal hydromorphone administered

Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	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. Hydromorphone: To be administered by intranasal route using mucosal atomization device.
Measure Participants	35
Mean (95% Confidence Interval) [units on a scale]	4.7

2. Secondary Outcome

Title	Number of Minor Adverse Events
Description	Lightheadedness, dizziness; confusion; sleepy, drowsy, tiredness; nausea; vomiting; itchiness, warm sensation; dry mouth; bad taste in mouth; rhinitis.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	Children who received intranasal hydromorphone
Measure Participants	35
Number [Minor adverse events]	39

3. Secondary Outcome

Title	Number of Major Adverse Events
Description	Oxygen desaturation, respiratory depression, hypotension, bradycardia, need for supplemental oxygen, bag-mask ventilation, airway support intervention, administration naloxone.
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	Children who received intranasal hydromorphone
Measure Participants	35
Number [Major adverse events]	0

4. Secondary Outcome

Title	Score on Verbal Numeric Rating Scale
Description	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
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Decrease in pain score one hour after terminal dose of intranasal hydromorphone administered

Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	Children who received intranasal hydromorphone
Measure Participants	35
Mean (95% Confidence Interval) [units on a scale]	5.1

Adverse Events

Time Frame	6 hours
Arm/Group Title	Intranasal Hydromorphone
Arm/Group Description	Children who received intranasal hydromorphone
All Cause Mortality
	Intranasal Hydromorphone
	Affected / at Risk (%)	# Events
Total	0/35 (0%)
Serious Adverse Events
	Intranasal Hydromorphone
	Affected / at Risk (%)	# Events
Total	0/35 (0%)
Other (Not Including Serious) Adverse Events
	Intranasal Hydromorphone
	Affected / at Risk (%)	# Events
Total	22/35 (62.9%)
Gastrointestinal disorders
Vomiting	0/35 (0%)
General disorders
Sleepy, drowsy, or tired	11/35 (31.4%)
Bad taste in mouth	8/35 (22.9%)
Lightheaded, dizzy	8/35 (22.9%)
Dry mouth	5/35 (14.3%)
Rhinitis	3/35 (8.6%)
Nausea	2/35 (5.7%)
Warm sensation	0/35 (0%)
Nervous system disorders
Confusion	1/35 (2.9%)
Skin and subcutaneous tissue disorders
Itchiness	1/35 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.