Musculoskeletal InjuryPhase 2No OUCHNCT03767933
Non-Steroidal or Opioid Analgesia Use for Children With Musculoskeletal Injuries
A Phase 2 study testing Ibuprofen, Acetaminophen and Hydromorphone in people with Musculoskeletal Injury, run by University of Alberta at 6 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Musculoskeletal Injury
- What is being tested?
- Ibuprofen, Acetaminophen and Hydromorphone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 710 participants
- Where
- 6 sitesCanada
- Study dates
- 20 Apr 2019to 22 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Canada6 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A9
Stollery Children's Hospital Emergency Department
Edmonton, Alberta, T6G 2B7
Childrens Hospital at London Health Sciences
London, Ontario, N6A 5W9
CHU Sainte-Justine
Montreal, Quebec, HT3 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Children's Hospital of Winnipeg
Winnipeg, Manitoba, R3A 1S1
About this study
Official title: A Study of Non-Steroidal or Opioid Analgesia Use for Children With Musculoskeletal Injuries: The No OUCH Trials
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).
Read more
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.
Read the detailed description
Rationale:
Multiple national and international organizations, including the American Academy of Pediatrics (AAP), have voiced concern over the emergency departments' (EDs) ability and willingness to provide appropriate analgesia for children's pain. Musculoskeletal (MSK) injury is a very common cause for ED visits for children with pain, with a child's risk of sustaining a fracture ranging from 27-42% by the age of 16 years. MSK injury is known to generate moderate to severe pain in most children and the ED serves as the critical entry point for these injured children. Despite three decades of pain research in this area, recent evidence confirms that ED pain management in children is still suboptimal. A retrospective cohort study of children presenting to the ED with an isolated long-bone fracture showed almost 1/3 received inadequate medication and 59% received no pain medications during the critical first hour of assessment. Previous studies have demonstrated that only 35% of children presenting to a Canadian pediatric ED with fractures or severe sprains received any analgesic. Further, a medical record review of two Canadian EDs showed unacceptably long delays in provision of initial analgesia, with children waiting a mean of 118 minutes to the provision of first analgesia.
The AAP's consensus statement on the assessment and management of pain in children recommends acetaminophen, ibuprofen, and opioids as the top three medication choices for the treatment of acute pain in children. These are also the top three most commonly used treatments in the ED for children with MSK injury pain. It stands to reason that clinicians (and certainly patients and their families) would prefer medication that has the best efficacy and safety profile. Although not based on robust evidence, there has recently been a concerted movement to limit opioid use in children. This is due, in part, to recent controversial publications and the Centre for Disease Control (CDC)'s position statement regarding opioid use in adults. Clinicians are increasingly less likely to prescribe oral opioids to younger children, and caregivers are increasingly less willing to accept or administer them.
Clinicians are currently seeking effective (and for many, non-opioid) oral analgesic options for their pediatric patients. Researchers have yet to identify the optimal acute pain management strategy for children with a suspected fracture, as very few studies of analgesic combination therapy for this injury exist, and monotherapy has been shown to be inadequate 50% of the time. This team's previous work has demonstrated that a combination of oral morphine with ibuprofen was no more effective and was less safe than oral ibuprofen, alone, for suspected fracture pain. Similarly, oxycodone was no more effective and was less safe than ibuprofen for post-discharge fracture pain. There is some emerging work from non-ED settings to suggest that oral hydromorphone may be an effective alternative to these two opioid medications. The investigators wish to study if acetaminophen or hydromorphone, when added to ibuprofen, offers more clinical pain relief than ibuprofen alone. They also wish to study if the combination of hydromorphone and ibuprofen is more clinically effective than the combination of acetaminophen with ibuprofen. This study, which will consist of two clinical trials, will inform health-care decisions by providing evidence for the effectiveness and safety of commonly prescribed analgesic combination therapies, and compare them to the most commonly used monotherapy, ibuprofen.
Methods:
This study will be comprised of two Phase 2, six-centre, randomized, double blind, placebo-controlled trials that will be run simultaneously. These two 'sister trials will be run simultaneously within this novel preference-informed complementary trial design. 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.
Those willing to consider an Opioid will be randomized to receive either single-dose: (a) oral ibuprofen (10mg/kg, max 600mg) plus 2 placebos (both oral hydromorphone and acetaminophen), OR (b) oral ibuprofen (10mg/kg, max 600mg) + oral acetaminophen (15 mg/kg, max 1000mg) plus hydromorphone placebo OR (c) oral ibuprofen (10mg/kg) + oral hydromorphone (0.05 mg/kg, max 5 mg) plus acetaminophen placebo. Those not willing to consider an opioid will be enrolled in the Non-Opioid trial and will be randomized to receive a single dose of (a) oral ibuprofen (10mg/kg, max 600mg) + oral acetaminophen (15 mg/kg, max 1000mg) OR (b) oral ibuprofen (10mg/kg, max 600mg) + oral acetaminophen placebo. Those without a preference for either trial will be assigned to the Opioid trial, as this one includes all three options of possible medication combinations. The investigators will measure pain scores, assess safety, and acquire other study measures, at designated study time points.
- Conditions
- Musculoskeletal Injury
- Being tested
- Ibuprofen, Acetaminophen, Hydromorphone, Acetaminophen placebo, Hydromorphone placebo
- Keywords
- Pediatrics, Emergency, Analgesia, Opioids, Combination therapy, Ibuprofen, Acetaminophen, Hydromorphone
- Medical subject headings
- Emergencies, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbuprofenDrug
Also called Advil, Motrin
10mg/kg, maximum 600mg; Oral liquid
AcetaminophenDrug
Also called Tylenol, Tempra
15mg/kg, maximum 1000mg; Oral liquid
HydromorphoneDrug
Also called Dilaudid, pms-Hydromorphone
0.05mg/kg, maximum 5 mg; Oral liquid
Acetaminophen placeboDrug
Oral liquid
Hydromorphone placeboDrug
Oral liquid
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Ibuprofen; Drug: Hydromorphone; Drug: Acetaminophen placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 60 minutes post study drug administration (ie. T-60)
Secondary outcomes (14)
Pain Score <3
The proportion of patients with a vNRS pain score <3 at 60 minutes. 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.
Measured: At 60 minutes post study drug administration (ie. T-60)
Pain Score Reduction of at least 2 points out of 10
The proportion of patients with a vNRS pain score reduction of at least 2 points out of 10. 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.
Measured: At 60 minutes post study drug administration (ie. T-60)
Between Group Pain Scores
Between group differences in vNRS pain scores. 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.
Measured: 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
Self-reported caregiver and child satisfaction with pain relief and acceptability of study medications, using a previously employed 5 point Likert scale. This scale ranges from very satisfied to very dissatisfied for caregivers, and ranges from very happy to very sad for children.
Measured: At the time of discharge from the emergency department (approximately 3 hours after time of recruitment)
Length of Stay
Emergency Department length of stay
Measured: At the time of discharge from the emergency department (approximately 3 hours after time of recruitment)
Missed Fractures or Dislocations
Frequency of missed fractures or dislocations
Measured: In the 1 week following administration of study medication
Additional Analgesic Requirements
Proportion of children administered a rescue analgesic
Measured: In the 60 minutes following administration of study medication
Time to Effective Analgesia
Time to effective analgesia, defined as the first vNRS pain score <3 post-intervention
Measured: At 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
VAS Pain Scores
Children's self-reported pain intensity on the Visual Analog Scale (VAS). The VAS consists of a straight line with the anchor 'no pain' on one end and 'the worst imaginable pain' at the other end. It is a validated measure for the assessment of pain in children.
Measured: At 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
FPS-R Pain Scores
Children's self-reported pain intensity on the Faces Pain Scale-Revised (FPS-R). The FPS-R consists of 6 faces, from left to right, each showing a greater level of pain than the previous one, with scores varying from 0 (no pain), 2, 4, 6, 8, and 10 (very much pain). The FPS-R is a validated measure for the assessment of pain in children.
Measured: At 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
Adverse Events
Proportion of children with adverse events related to study drug administration.
Measured: Up to 24 hours post study drug administration
Serious Adverse Events
Proportion of children with any serious adverse events during the study period
Measured: Up to 24 hours post study drug administration
RSS
Proportion of children in each study group with a Ramsay Sedation Score (RSS) score between 1 to 3
Measured: At 0, 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
Specific Adverse Events
Proportion of children with each specific adverse event type during the study period
Measured: Up to 24 hours post study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2018
- Study start20 Apr 2019
- Primary completion9 Mar 2023
- Study completion22 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Musculoskeletal InjuryStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 710 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manitoba, Centre hospitalier de l'Université de Montréal (CHUM), University of Calgary, The Hospital for Sick Children, University of Ottawa, Western University
- Responsible party
- Sponsor
- Investigators
- Samina Ali, MD, Principal investigator, University of Alberta/Stollery Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03767933
- Sponsor's protocol ID
- Pro00073476
- Acronym
- No OUCH
- Status last verified
- Jan 2023
- First submitted
- 21 Nov 2018
- Last updated
- 19 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: This study will comply with the CIHR Open Access Policy. The trials will be registered at ClinicalTrials.gov, and results information from this study will be submitted to ClinicalTrials.gov. Also, every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers 2 years after the completion of the primary endpoint by contacting the Women and Children\'s Health Research Institute (WCHRI) Data Coordinating Center (DCC). Conduct, reporting, editing, and publication of resultant scholarly work will be guided by the International Committee of Journal Medical Editors (ICJME)'s published recommendations. The identity of participants will not be revealed in any published data or in presentation of the information obtained as a result of this study.
Publications
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 Mar 10;335(10):863-873. doi: 10.1001/jama.2025.25033.
PubMed 41505155Ali 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.
PubMed 37023945Heath 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.
PubMed 32883371Ali 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.
PubMed 32565458
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Non-Steroidal or Opioid Analgesia Use for Children With Musculoskeletal Injuries: The No OUCH Trials
- ClinicalTrials.gov ID
- NCT03767933
- Acronym / sponsor ID
- No OUCH / Pro00073476
- Conditions
- Musculoskeletal Injury
- Keywords
- Pediatrics, Emergency, Analgesia, Opioids, Combination therapy, Ibuprofen, Acetaminophen, Hydromorphone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 710 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- University of Manitoba, Centre hospitalier de l'Université de Montréal (CHUM), University of Calgary, The Hospital for Sick Children, University of Ottawa, Western University
- Study start
- 20 Apr 2019 (actual)
- Primary completion
- 9 Mar 2023 (actual)
- Study completion
- 22 Mar 2023 (actual)
- First posted
- 7 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rationale:
Multiple national and international organizations, including the American Academy of Pediatrics (AAP), have voiced concern over the emergency departments' (EDs) ability and willingness to provide appropriate analgesia for children's pain. Musculoskeletal (MSK) injury is a very common cause for ED visits for children with pain, with a child's risk of sustaining a fracture ranging from 27-42% by the age of 16 years. MSK injury is known to generate moderate to severe pain in most children and the ED serves as the critical entry point for these injured children. Despite three decades of pain research in this area, recent evidence confirms that ED pain management in children is still suboptimal. A retrospective cohort study of children presenting to the ED with an isolated long-bone fracture showed almost 1/3 received inadequate medication and 59% received no pain medications during the critical first hour of assessment. Previous studies have demonstrated that only 35% of children presenting to a Canadian pediatric ED with fractures or severe sprains received any analgesic. Further, a medical record review of two Canadian EDs showed unacceptably long delays in provision of initial analgesia, with children waiting a mean of 118 minutes to the provision of first analgesia.
The AAP's consensus statement on the assessment and management of pain in children recommends acetaminophen, ibuprofen, and opioids as the top three medication choices for the treatment of acute pain in children. These are also the top three most commonly used treatments in the ED for children with MSK injury pain. It stands to reason that clinicians (and certainly patients and their families) would prefer medication that has the best efficacy and safety profile. Although not based on robust evidence, there has recently been a concerted movement to limit opioid use in children. This is due, in part, to recent controversial publications and the Centre for Disease Control (CDC)'s position statement regarding opioid use in adults. Clinicians are increasingly less likely to prescribe oral opioids to younger children, and caregivers are increasingly less willing to accept or administer them.
Clinicians are currently seeking effective (and for many, non-opioid) oral analgesic options for their pediatric patients. Researchers have yet to identify the optimal acute pain management strategy for children with a suspected fracture, as very few studies of analgesic combination therapy for this injury exist, and monotherapy has been shown to be inadequate 50% of the time. This team's previous work has demonstrated that a combination of oral morphine with ibuprofen was no more effective and was less safe than oral ibuprofen, alone, for suspected fracture pain. Similarly, oxycodone was no more effective and was less safe than ibuprofen for post-discharge fracture pain. There is some emerging work from non-ED settings to suggest that oral hydromorphone may be an effective alternative to these two opioid medications. The investigators wish to study if acetaminophen or hydromorphone, when added to ibuprofen, offers more clinical pain relief than ibuprofen alone. They also wish to study if the combination of hydromorphone and ibuprofen is more clinically effective than the combination of acetaminophen with ibuprofen. This study, which will consist of two clinical trials, will inform health-care decisions by providing evidence for the effectiveness and safety of commonly prescribed analgesic combination therapies, and compare them to the most commonly used monotherapy, ibuprofen.
Methods:
This study will be comprised of two Phase 2, six-centre, randomized, double blind, placebo-controlled trials that will be run simultaneously. These two 'sister trials will be run simultaneously within this novel preference-informed complementary trial design. 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.
Those willing to consider an Opioid will be randomized to receive either single-dose: (a) oral ibuprofen (10mg/kg, max 600mg) plus 2 placebos (both oral hydromorphone and acetaminophen), OR (b) oral ibuprofen (10mg/kg, max 600mg) + oral acetaminophen (15 mg/kg, max 1000mg) plus hydromorphone placebo OR (c) oral ibuprofen (10mg/kg) + oral hydromorphone (0.05 mg/kg, max 5 mg) plus acetaminophen placebo. Those not willing to consider an opioid will be enrolled in the Non-Opioid trial and will be randomized to receive a single dose of (a) oral ibuprofen (10mg/kg, max 600mg) + oral acetaminophen (15 mg/kg, max 1000mg) OR (b) oral ibuprofen (10mg/kg, max 600mg) + oral acetaminophen placebo. Those without a preference for either trial will be assigned to the Opioid trial, as this one includes all three options of possible medication combinations. The investigators will measure pain scores, assess safety, and acquire other study measures, at designated study time points.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Non-Opioid Trial: Arm 1 | Active comparator | Drug: Ibuprofen, Drug: Acetaminophen placeboOral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen placebo, both administered once during the study at the time of recruitment. |
| Non-Opioid Trial: Arm 2 | Experimental | Drug: Ibuprofen, Drug: AcetaminophenOral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen (15mg/kg, maximum 1000mg), both administered once during the study at the time of recruitment. |
| Opioid Trial: Arm 1 | Active comparator | Drug: Ibuprofen, Drug: Acetaminophen placebo, Drug: Hydromorphone placeboOral ibuprofen (10mg/kg, max 600mg) + Oral acetaminophen placebo + Oral hydromorphone placebo, all administered once during the study at the time of recruitment. |
| Opioid Trial: Arm 2 | Experimental | Drug: Ibuprofen, Drug: Acetaminophen, Drug: Hydromorphone placeboOral 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. |
| Opioid Trial: Arm 3 | Experimental | Drug: Ibuprofen, Drug: Hydromorphone, Drug: Acetaminophen placeboOral 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. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbuprofenAlso: Advil, Motrin10mg/kg, maximum 600mg; Oral liquid | Drug | Non-Opioid Trial: Arm 1, Non-Opioid Trial: Arm 2, Opioid Trial: Arm 1, Opioid Trial: Arm 2, Opioid Trial: Arm 3 |
| AcetaminophenAlso: Tylenol, Tempra15mg/kg, maximum 1000mg; Oral liquid | Drug | Non-Opioid Trial: Arm 2, Opioid Trial: Arm 2 |
| HydromorphoneAlso: Dilaudid, pms-Hydromorphone0.05mg/kg, maximum 5 mg; Oral liquid | Drug | Opioid Trial: Arm 3 |
| Acetaminophen placeboOral liquid | Drug | Non-Opioid Trial: Arm 1, Opioid Trial: Arm 1, Opioid Trial: Arm 3 |
| Hydromorphone placeboOral liquid | Drug | Opioid Trial: Arm 1, Opioid Trial: Arm 2 |
Primary outcome
vNRS Pain Score
Time frame: At 60 minutes post study drug administration (ie. T-60)
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.
14 secondary outcomes
Pain Score <3
Time frame: At 60 minutes post study drug administration (ie. T-60)
Pain Score Reduction of at least 2 points out of 10
Time frame: At 60 minutes post study drug administration (ie. T-60)
Between Group Pain Scores
Time frame: 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
Time frame: At the time of discharge from the emergency department (approximately 3 hours after time of recruitment)
Length of Stay
Time frame: At the time of discharge from the emergency department (approximately 3 hours after time of recruitment)
Missed Fractures or Dislocations
Time frame: In the 1 week following administration of study medication
Additional Analgesic Requirements
Time frame: In the 60 minutes following administration of study medication
Time to Effective Analgesia
Time frame: At 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
VAS Pain Scores
Time frame: At 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
FPS-R Pain Scores
Time frame: At 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
Adverse Events
Time frame: Up to 24 hours post study drug administration
Serious Adverse Events
Time frame: Up to 24 hours post study drug administration
RSS
Time frame: At 0, 30, 60, 90, and 120 minutes post study drug administration, and at the Time of Medical Examination (approximately 90 minutes after time of recruitment) and Time of X-Ray (approximately 60 minutes after time of recruitment)
Specific Adverse Events
Time frame: Up to 24 hours post study drug administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 41505155Ali 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 Mar 10;335(10):863-873. doi: 10.1001/jama.2025.25033.
- Derived from this study: PubMed 37023945Ali 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.
- Derived from this study: PubMed 32883371Heath 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.
- Derived from this study: PubMed 32565458Ali 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.
- Individual participant dataSharing planned: Yes. This study will comply with the CIHR Open Access Policy. The trials will be registered at ClinicalTrials.gov, and results information from this study will be submitted to ClinicalTrials.gov. Also, every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers 2 years after the completion of the primary endpoint by contacting the Women and Children\'s Health Research Institute (WCHRI) Data Coordinating Center (DCC). Conduct, reporting, editing, and publication of resultant scholarly work will be guided by the International Committee of Journal Medical Editors (ICJME)'s published recommendations. The identity of participants will not be revealed in any published data or in presentation of the information obtained as a result of this study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samina Ali, MD principal investigator
University of Alberta/Stollery Children's Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibuprofen, Acetaminophen and Hydromorphone in people with Musculoskeletal Injury, run by University of Alberta at 6 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
vNRS Pain Score (time frame: At 60 minutes post study drug administration (ie. T-60)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03767933, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.