Oral vs IV Acetaminophen for Long-bone Fracture in Children

Phase 4

Recruiting

• Conditions: Pain
• Interventions: Drug: Acetaminophen IV; Drug: Acetaminophen

• Registration Number: NCT05557344
• Lead Sponsor: Dr. Niina Kleiber

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.

Study Timeline

• Study Start: 2021-04-21
• Study First Submitted: 2022-08-24
• Status Verified: 2022-09
• Study First Submitted QC: 2022-09-23
• Last Update Submitted: 2022-09-23
• Study First Posted: 2022-09-28
• Last Update Posted: 2022-09-28
• Primary Completion: 2023-09-01
• Study Completion: 2024-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV acetaminophen arm	Acetaminophen IV	they will receive IV acetaminophen, placebo oral
Oral acetaminophen arm	Acetaminophen	they will receive oral acetaminophen, placebo (saline) IV

Primary Outcome Measures

Name	Time	Method
Change in pain scores	During 24h (starting with the first dose of study drug)	Pain scores within the first 24 hours following initiation of study drug, using the scales Face, Legs, Activity, Cry, Consolability (FLACC, 0-2 per item for a total of 10, 10 being the worst pain) and verbal numerical rating (VNR, 0-10, 10 being the worst pain).
Difference in quantity of rescue opioids	During 24h (starting with the first dose of study drug)	Quantity of rescue opioids (morphine equivalent in mg/kg) within the first 24 hours following initiation of study drug

Secondary Outcome Measures

Name	Time	Method
Adverse events	During 24h (starting with the first dose of study drug)	Any other adverse effect whether or not attributed to the study drug will be carefully recorded. Opioid-related adverse effects will be recorded (pruritus, time to first bowel movement, nausea (self-reported), vomiting, days of bladder catheterization, oxygen supplementation, episodes of respiratory depression (\< 10/min in children older than 5 years), use of diphenhydramine, naloxone, antiemetics, laxatives).
Determination of oral bioavailability	During 24 hours after the first dose of study drug	Blood level of acetaminophen will be determined

Trial Locations

Locations (1)

CHU Sainte-Justine; 🇨🇦 Montréal, Quebec, Canada