Clinical trial NCT05557344: Oral vs IV Acetaminophen for Long-bone Fracture in Children
Official title: Oral Versus Intravenous Acetaminophen for the Treatment of Pain Secondary to Long Bone Fracture Requiring Surgery in Children
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pain
Keywords: pain
analgesics
pediatrics
acetaminophen
orthopedics
pharmacokinetics
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2022-09-28
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Intravenous (IV) acetaminophen entered the Canadian market recently and children with acute pain following a trauma are ideal candidates for the IV formulation as it may improve analgesia and consequently decrease the amount of opioids needed to achieve pain control. Due to the limited data on bioavailability, adverse effect profile and efficacy of IV versus oral acetaminophen, it is of paramount importance to generate evidence-based data to guide clinicians with a rational choice of route of administration of acetaminophen.

Therefore, we propose a pilot study to inform a future large randomized controlled trial (RCT) to compare pharmacokinetics, feasibility, preliminary effects and side effects profile of oral versus IV acetaminophen in children admitted for surgical fixation of a long-bone fracture.

Detailed description: Patients admitted for a long-bone fracture needing surgical fixation are generally initially treated with intranasal and/or IV opioids in association to oral acetaminophen and ibuprofen. Following surgery they are treated with a combination of morphine and acetaminophen. To address the issue of opioid epidemics, the Pediatric Orthopaedic Society of North America recommends reduction of their prescription as much as possible by promoting, among others, use of multimodal analgesia after surgery. The current proposal aims to improve post-operative pain control in children following a surgical fixation of a long-bone fracture and decrease the use of opioids through better co-analgesia. As such, this study aims to assess the pharmacokinetics (PK) and the efficacy of oral versus IV formulations of acetaminophen after surgery for long bone fractures in children.

Eligibility criteria: Inclusion Criteria:

* Likely to undergo surgery for a long-bone fracture
* Aged between 2-18 years (IV acetaminophen is approved for children ≥2 years)
* IV line per standard of care

Exclusion Criteria:

* Contraindication to oral drug administration
* Patients unable to take oral solution
* Known hypersensitivity or allergy to acetaminophen or any of the excipients in the IV or oral formulation
* Use of any medication known to interact with acetaminophen including, but not restricted to phenytoin and carbamazepine (1)
* Pregnancy
* Known Hepatic insufficiency or hepatic disease
* Known or diagnosed severe renal failure
* Multiple trauma (more than two long bone fractures)
* Hemodynamic or respiratory compromise
* Altered level of consciousness (Glasgow coma scale \<15)

Primary outcomes:
measure: Change in pain scores
timeFrame: During 24h (starting with the first dose of study drug)
measure: Difference in quantity of rescue opioids
timeFrame: During 24h (starting with the first dose of study drug)
Secondary outcomes:
measure: Adverse events
timeFrame: During 24h (starting with the first dose of study drug)
measure: Determination of oral bioavailability
timeFrame: During 24 hours after the first dose of study drug
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Niina Kleiber, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ulrich M, Chamberland M, Bertoldi C, Garcia-Bournissen F, Kleiber N. Newly approved IV acetaminophen in Canada: Switching from oral to IV acetaminophen. Is IV worth the price difference? A systematic review. Paediatr Child Health. 2021 Mar 13;26(6):337-343. doi: 10.1093/pch/pxaa137. eCollection 2021 Oct.