Oral vs IV Acetaminophen for Long-bone Fracture in Children

NCT ID: NCT05557344

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-21
• Study Completion Date: 2024-03-01

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.

Conditions

Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Oral acetaminophen arm

they will receive oral acetaminophen, placebo (saline) IV

Group Type: ACTIVE_COMPARATOR

Acetaminophen

Intervention Type: DRUG

A liquid oral acetaminophen suspension will be administered regularly every 6h at a dose of 15mg/kg (maximum single dose: 1g). An IV infusion of NaCl 0.9% corresponding to the volume of IV acetaminophen will be administered as a 15-minute intravenous infusion at the same time as the oral dose. PrACETAMINOPHEN INJECTION ® is a clear and colorless liquid undistinguishable from NaCl 0.9%.

IV acetaminophen arm

they will receive IV acetaminophen, placebo oral

Group Type: ACTIVE_COMPARATOR

Acetaminophen IV

Intervention Type: DRUG

An IV infusion of 15mg/kg of acetaminophen (PrACETAMINOPHEN INJECTION, AVIR Pharma Inc.) (maximum single dose:1g) will be administered regularly every 6h as a 15-minute intravenous infusion. At the same time, an oral placebo with similar appearance as the corresponding acetaminophen oral solution will be administered.

Interventions

Acetaminophen IV

An IV infusion of 15mg/kg of acetaminophen (PrACETAMINOPHEN INJECTION, AVIR Pharma Inc.) (maximum single dose:1g) will be administered regularly every 6h as a 15-minute intravenous infusion. At the same time, an oral placebo with similar appearance as the corresponding acetaminophen oral solution will be administered.

Intervention Type: DRUG

Acetaminophen

A liquid oral acetaminophen suspension will be administered regularly every 6h at a dose of 15mg/kg (maximum single dose: 1g). An IV infusion of NaCl 0.9% corresponding to the volume of IV acetaminophen will be administered as a 15-minute intravenous infusion at the same time as the oral dose. PrACETAMINOPHEN INJECTION ® is a clear and colorless liquid undistinguishable from NaCl 0.9%.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dr. Niina Kleiber

OTHER

Sponsor Role: lead

Responsible Party

Dr. Niina Kleiber

Paediatrician and Clinical Pharmacologist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Niina Kleiber, MD PhD

Role: PRINCIPAL_INVESTIGATOR

St. Justine's Hospital

Locations

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Niina Kleiber, MD

Role: CONTACT

niina.kleiber.med@ssss.gouv.qc.ca

(514) 3454931

Evelyne Trottier

Role: CONTACT

evelyne.doyon-trottier.med@ssss.gouv.qc.ca

(514) 3454931

Facility Contacts

Niina kleiber, MD

Role: primary

niina.kleiber.med@ssss.gouv.qc.ca

514 3454931

References

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.

Reference Type: BACKGROUND

PMID: 34676011 (View on PubMed)

Other Identifiers

Acetaminophen IV vs PO

Identifier Type: -

Identifier Source: org_study_id