Clinical Trial Details
— Status: Withdrawn
Administrative data
NCT number |
NCT02985177 |
Other study ID # |
99 |
Secondary ID |
|
Status |
Withdrawn |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
January 2020 |
Est. completion date |
September 2021 |
Study information
Verified date |
October 2022 |
Source |
St. Justine's Hospital |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
MSK-I is the most 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-I is known to generate
moderate to severe pain in most children and the ED serves as the critical entry point for
these injured children. This study aims to provide rapid and sustained pain management for
children presenting with a MSK-I in the ED. The investigators will compare the efficacy of
two possible medication combinations of fentanyl intranasal (1.0 mcg/kg) + oral ibuprofen (10
mg/kg) and fentanyl intranasal (2.0 mcg/kg) + oral ibuprofen (10 mg/kg) for the rapid,
adequate and sustained pain management of children with suspected fracture.
The investigators believe that the combination of different dosage of intranasal fentanyl
with ibuprofen will lead to better pain treatment by providing a consistent and adequate
level of analgesia throughout the entire ED visit, including prior to physician exam and
during painful radiologic procedures.
Description:
Pain management for children with a suspected fracture is suboptimal in the Emergency
Department (ED). This type of musculoskeletal injury (MSK-I) often generates moderate to
severe pain (> 49 mm on 0 to 100 mm Visual Analogue Scale (VAS)), and requires rapid and
sustained pain management for the duration of the physical examination, diagnostic imaging
(X-Ray), immobilization and occasionally fracture reduction. Current standard care includes
the use of oral ibuprofen (IBU), a non-steroidal anti-inflammatory drug (NSAID), for
mild-to-moderate MSK-I pain in the ED. However, ibuprofen has been shown to be inadequate for
moderate-to-severe pain when used alone. A number of small/single centre studies suggest that
intranasal fentanyl (INF) is effective for rapidly decreasing MSK-I related pain in children
with a quick onset of 10 minutes and a peak action of 20 minutes. However, the duration of
its analgesic effect is limited to a maximum of 60 minutes, which does not provide an optimal
pain management for the duration of the ED stay, which typically lasts up to three hours.
Typically, patients with a fracture have sustained pain throughout their ED stay due to
imaging, splinting and repeated physical exams. Our objective is to examine the efficacy of a
combination of intranasal and oral analgesics for pain management in children presenting to
the ED with a suspected fracture. Our primary research question: For children presenting to
the ED with a suspected fracture, is a combination of INF1.0 (1.0 mcg/kg, maximum dose of 100
mcg) and IBU (10 mg/kg, maximum dose of 600 mg) more efficacious than a combination of INF2.0
(2.0 mcg/kg, maximum dose of 100 mcg) and oral ibuprofen (10 mg/kg, maximum dose of 600 mg)
to decrease pain at 15 minutes post-administration? Our primary hypothesis is: A combination
of INF2.0 and IBU will be more efficacious than a combination of INF1.0 and IBU to decrease
pain at 15 minutes post-administration.
Methods. Design: This study is a single-blind, two-arm, three-centre RCT of a combination of
analgesics for pain management of children presenting to the ED with a suspected fracture
will be performed. Settings: Children will be recruited in the following EDs: CHU
Sainte-Justine (Montreal, QC), Stollery Children's Hospital (Edmonton, AB), and Children's
Hospital of the London Health Sciences Centre (London, ON). Sample. Inclusion criteria: Will
be include children: (a) with a pain score >49 mm on VAS at triage, (b) between the ages of 7
and 17 years, (c) presenting to the ED with a suspected fracture of the upper or lower limb,
and (d) who can communicate in either French or English. Exclusion criteria: Will be exclude
children with (a) known allergy to fentanyl or ibuprofen, (b) triage nurse suspicion of child
abuse, (c) inability to self-report pain, (d) chronic pain that necessitates daily analgesic
use, (e) NSAID or opioid analgesic use within the three hours prior to ED presentation, (f)
trauma to >1 limb, (g) known hepatic or renal disease/dysfunction, (h) known bleeding
disorder, (i) neuro-cognitive disability that precludes assent and/or participating in the
study, (j) known history of obstructive sleep apnea (k) a suspected fracture of the nose, or
(l) significant head injury, as determined by the clinical team/triage nurse.
Allocation and Randomization: A biostatistician, independent to our study team, will generate
the randomization scheme that will consist of a computer-generated random listing of the
treatment using a 1:1 allocation scheme. Randomization will be stratified by center using
block-randomization (with permuted block sizes). Enrolled children will be allocated to (a)
INF 1.0 mcg/kg (up to a maximum of 100 mcg) via intranasal atomization + oral IBU 10 mg/kg
(up to a maximum of 600 mg) OR (b) INF 2.0 mcg/kg (up to a maximum of 100 mcg) via intranasal
atomization + oral IBU 10 mg/kg (up to a maximum of 600 mg.
Sample Size: Accounting for a 10% attrition rate, we determined that enrollment of 172
participants would provide at least 90 % power to detect a 10 mm absolute difference in mean
pain scores between groups at 15 minutes post-medication administration (T-15), at an alpha
level of 5 %.
Primary efficacy outcome: Mean difference in pain scores between groups at 15 minutes
post-medication administration (T-15) using the Visual Analogue Scale (VAS). Secondary
outcomes: (a) Mean differences in pain scores between groups at 30 min (T-30), 60 min (T-60),
90 min (T-90), 120 min (T-120) after medication administration, during the medical
examination (T-ME), and during radiographic procedure (T-XR), (b) the proportion of children
administered a rescue analgesic in the 60 minutes following administration of study
medication, (c) the proportion of children with adverse events at T-15, T-30, T-60, T-90,
T-120, T-ME and T-XR, (d) the proportion of children with serious adverse events at T-15,
T-30, T-60, T-90, T-120, T-ME and T-XR, (e) the proportion of children in each group with an
RSS score > 3 (f) satisfaction of children and parents regarding pain management (T-120).
Relevance: In response to the persistent problem of inadequate and delayed analgesia, the
investigators believe that a combination of rapidly acting (INF) and longer-acting (oral
ibuprofen) medications will address both the delay in the time to effective analgesia and
overall under-treatment of suspected fracture pain. The team anticipate that an RCT
demonstrating the efficacy of a combination of fast and long-acting analgesics will
significantly improve the treatment for children with a suspected fracture in the ED. The
investigators hypothesize that use of INF2.0 and oral IBU will provide rapid pain relief that
is sustained for the duration of the ED visit. Promotion of adequate acute pain treatment of
children presenting to the ED will prevent the known short and long-term effects of
inadequately treated pain in children previously demonstrated by our team, including
unpleasant memories, stress and anxiety upon future visits to healthcare and compromised
functional outcomes such as missed school.