Non-Steroidal or Opioid Analgesia Use for Children With Musculoskeletal Injuries

NCT03767933 | Completed Phase 2

• 1 other identifier: Pro00073476
• Study Type: interventional
• Target: 710
• Locations: 1 country
• Sites: 6

Brief Summary

Musculoskeletal (MSK) injuries, including limb injuries, are the most common cause for Emergency Department (ED) visits for children with pain. Broken arms and legs are known to cause moderate to severe pain in most children, yet previous research shows that children's pain in the emergency department is still under-treated. Further, children are less likely to receive appropriate pain medicine than adults with similar injuries. The purpose of this research study is to compare the effectiveness and safety of 3 different possible medication combinations, for the pain management of children with acute MSK limb injuries. The pain medicines the investigators are studying are ibuprofen (Advil/Motrin), acetaminophen (Tylenol/Tempra), and hydromorphone (Dilaudid). This study will consist of 2 trials that will be run simultaneously. Eligible caregiver/ child pairs presenting to the emergency department with acute MSK limb injury will decide in which trial they wish to participate: the Opioid trial or the Non-Opioid trial. If they select the Non-opioid trial, they will have an equal chance of receiving either (a) Ibuprofen OR (b) Ibuprofen and acetaminophen. If they select the Opioid trial, they will have an equal chance of receiving either (a) Ibuprofen OR (b) Ibuprofen and acetaminophen OR (c) Ibuprofen and hydromorphone. Regardless of which study they choose, their child will, at minimum, receive Ibuprofen (Advil/Motrin) for their pain. All study medicines will be given in oral liquid form. This study will help the investigators figure out which pain medicine or combination of pain medicines works best for children with limb injuries. Promotion of adequate acute pain treatment of children presenting to the ED may help prevent the known short and long-term effects of inadequately treated pain in children, including unpleasant memories, stress and anxiety upon future visits to healthcare, and compromised functional outcomes such as missed school.

Conditions

Musculoskeletal Injury

Keywords

Pediatrics; Emergency; Analgesia; Opioids; Combination therapy; Ibuprofen; Acetaminophen; Hydromorphone

Outcome Measures

Primary Outcomes (1)

• vNRS Pain Score

  The self-reported vNRS pain score. The 11 point 0-10 verbal Numerical Rating Scale (vNRS) is the most commonly used pain measurement tool for our study age group and has been validated in a number of children's pain studies.

  At 60 minutes post study drug administration (ie. T-60)

Secondary Outcomes (14)

• Pain Score <3

  At 60 minutes post study drug administration (ie. T-60)

• Pain Score Reduction of at least 2 points out of 10

  At 60 minutes post study drug administration (ie. T-60)

• Between Group Pain Scores

  At 30, 60, 90, and 120 minutes post study drug administration, at Time of Medical Examination (approximately 90 minutes after time of recruitment) and at Time of X-Ray (approximately 60 minutes after time of recruitment)

• Satisfaction with Pain Relief

  At the time of discharge from the emergency department (approximately 3 hours after time of recruitment)

• Length of Stay

  At the time of discharge from the emergency department (approximately 3 hours after time of recruitment)

Study Arms (5)

Non-Opioid Trial: Arm 1

ACTIVE COMPARATOR

Oral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen placebo, both administered once during the study at the time of recruitment.

Drug: Ibuprofen; Drug: Acetaminophen placebo

Non-Opioid Trial: Arm 2

EXPERIMENTAL

Oral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen (15mg/kg, maximum 1000mg), both administered once during the study at the time of recruitment.

Drug: Ibuprofen; Drug: Acetaminophen

Opioid Trial: Arm 1

ACTIVE COMPARATOR

Oral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen placebo + Oral hydromorphone placebo, all administered once during the study at the time of recruitment.

Drug: Ibuprofen; Drug: Acetaminophen placebo; Drug: Hydromorphone placebo

Opioid Trial: Arm 2

EXPERIMENTAL

Oral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen (15mg/kg, maximum 1000mg) + Oral hydromorphone placebo, all administered once during the study at the time of recruitment.

Drug: Ibuprofen; Drug: Acetaminophen; Drug: Hydromorphone placebo

Opioid Trial: Arm 3

EXPERIMENTAL

Oral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen placebo + Oral hydromorphone (0.05mg/kg, maximum 5 mg), all administered once during the study at the time of recruitment.

Drug: Ibuprofen; Drug: Hydromorphone; Drug: Acetaminophen placebo

Interventions

Ibuprofen DRUG

10mg/kg, maximum 600mg; Oral liquid

Also known as: Advil, Motrin

Non-Opioid Trial: Arm 1; Non-Opioid Trial: Arm 2; Opioid Trial: Arm 1; Opioid Trial: Arm 2; Opioid Trial: Arm 3

Acetaminophen DRUG

15mg/kg, maximum 1000mg; Oral liquid

Also known as: Tylenol, Tempra

Non-Opioid Trial: Arm 2; Opioid Trial: Arm 2

Hydromorphone DRUG

0.05mg/kg, maximum 5 mg; Oral liquid

Also known as: Dilaudid, pms-Hydromorphone

Opioid Trial: Arm 3

Acetaminophen placebo DRUG

Oral liquid

Non-Opioid Trial: Arm 1; Opioid Trial: Arm 1; Opioid Trial: Arm 3

Hydromorphone placebo DRUG

Oral liquid

Opioid Trial: Arm 1; Opioid Trial: Arm 2

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Child aged 6-17 years
• Presenting to the emergency department with an acute limb injury (\<24 hours old) that is neither obviously deformed nor having neuro-vascular compromise (as assessed by the triage nurse)
• Self-reported pain score \> 5 on the 0 to 10 verbal Numerical Rating Scale at triage

You may not qualify if:

• Deemed to require immediate intravenous (IV) or intranasal (IN) pain medications by the clinical team
• Previously known hypersensitivity to study medications
• Acetaminophen or NSAID use within 3 hours prior to recruitment
• Opioid use within 1 hour prior to recruitment
• Caregiver and/or child cognitive impairment precluding the ability to self-report pain or respond to study questions
• Injury suspected to be due to non-accidental trauma/ child abuse (as assessed by the triage nurse or reported by the family)
• Suspected multi-limb fracture
• Chronic pain that necessitates daily analgesic use
• Hepatic or renal disease/dysfunction
• Bleeding disorder
• Known pregnancy
• Vomiting that precludes the ability to take oral medications (as determined by the family)
• Caregiver and/or child inability to communicate fluently in English or French in the absence of a native language interpreter
• Caregiver unavailable for follow-up
• Previous enrolment in the NO OUCH study

Sponsors & Collaborators

• University of Alberta: lead
• University of Manitoba: collaborator
• Centre hospitalier de l'Université de Montréal (CHUM): collaborator
• University of Calgary: collaborator
• The Hospital for Sick Children: collaborator
• University of Ottawa: collaborator
• Western University: collaborator

Study Sites (6)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A9, Canada

Location

Stollery Children's Hospital Emergency Department

Edmonton, Alberta, T6G 2B7, Canada

Location

Children's Hospital of Winnipeg

Winnipeg, Manitoba, R3A 1S1, Canada

Location

Childrens Hospital at London Health Sciences

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, HT3 1C5, Canada

Location

Related Publications (4)

• Ali S, Klassen TP, Candelaria P, Bhatt M, Sawyer S, Stang A, Yaskina M, Heath A, Pechlivanoglou P, Offringa M, Drendel AL, Hickes S, Poonai N; KidsCAN PERC Innovative Pediatric Clinical Trials No OUCH Study Team. Acetaminophen (Paracetamol) or Opioid Analgesia Added to Ibuprofen for Children's Musculoskeletal Injury: Two Randomized Clinical Trials. JAMA. 2026 Jan 8:e2525033. doi: 10.1001/jama.2025.25033. Online ahead of print.

  PMID: 41505155 DERIVED

• Ali S, Dworsky-Fried Z, Moir M, Bharadia M, Rajagopal M, Gouin S, Sawyer S, Pellerin S, Bourrier L, Poonai N, Stang A, Leung J, van Manen M; KidsCAN PERC Innovative Pediatric Clinical Trials No OUCH Study Team. Factors Influencing Parental Decision-Making Regarding Analgesia for Children with Musculoskeletal Injury-Related Pain: A Qualitative Study. J Pediatr. 2023 Jul;258:113405. doi: 10.1016/j.jpeds.2023.113405. Epub 2023 Apr 4.

  PMID: 37023945 DERIVED

• Heath A, Yaskina M, Hopkin G, Klassen TP, McCabe C, Offringa M, Pechlivanoglou P, Rios JD, Poonai N, Ali S; KidsCAN PERC Innovative Pediatric Clinical Trials No OUCH Study Group. Non-steroidal or opioid analgesia use for children with musculoskeletal injuries (the No OUCH study): statistical analysis plan. Trials. 2020 Sep 3;21(1):759. doi: 10.1186/s13063-020-04503-y.

  PMID: 32883371 DERIVED

• Ali S, Rajagopal M, Klassen T, Richer L, McCabe C, Willan A, Yaskina M, Heath A, Drendel AL, Offringa M, Gouin S, Stang A, Sawyer S, Bhatt M, Hickes S, Poonai N; KidsCAN PERC Innovative Pediatric Clinical Trials No OUCH Study Team. Study protocol for two complementary trials of non-steroidal or opioid analgesia use for children aged 6 to 17 years with musculoskeletal injuries (the No OUCH study). BMJ Open. 2020 Jun 21;10(6):e035177. doi: 10.1136/bmjopen-2019-035177.

  PMID: 32565458 DERIVED

MeSH Terms

Conditions

Emergencies; Agnosia

Interventions

Ibuprofen; Acetaminophen; Hydromorphone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Samina Ali, MD

  University of Alberta/Stollery Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Research staff, emergency department staff, and participants will be masked with respect to the allocated treatment. The data analyst will also be masked using codes that will not identify treatment groups until analysis is complete.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be comprised of two Phase 2, six-centre, randomized, double blind, placebo-controlled trials that will be run simultaneously. The investigators expect that the number of participants recruited and the time to completion of both trials will be more efficient as recruitment for both will occur simultaneously. They propose to conduct this study with a novel preference-informed complementary trial design, in which they will conduct two simultaneous 'sister' trials. Caregiver/child pairs presenting to the ED with acute MSK limb injury will decide in which trial they wish to participate: the Opioid trial or the Non-Opioid trial. The design of each trial will be informed by its sister, or complementary, trial. Once the caregiver/child pair has chosen their preferred trial, conduct within each trial will follow traditional randomized, double-blind placebo-controlled superiority trial methodology. Study endpoints will be identical for both trials within this study.

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: December 7, 2018
• Study Start: April 20, 2019
• Primary Completion: March 9, 2023
• Study Completion: March 22, 2023
• Last Updated: September 19, 2024

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data from this study may be requested from other researchers 2 years after the completion of the primary endpoint
• Access Criteria: Researchers will need to contact the WCHRI DCC for access to the data

Locations

CA (6)