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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Pain

Intervention / Treatment
-----------------
* Drug: Hydromorphone


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal hydromorphone<br>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<br>* To be administered by intranasal route using mucosal atomization device.<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intranasal, Hydromorphone, Pediatric, Emergency department