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Oral vs IV Acetaminophen for Long-bone Fracture in Children

Primary Purpose

Pain

Status

Recruiting

Phase

Phase 4

Locations

Canada

Study Type

Interventional

Intervention

Acetaminophen IV

Acetaminophen

About this trial

This is an interventional supportive care trial for Pain focused on measuring pain, analgesics, pediatrics, acetaminophen, orthopedics, pharmacokinetics

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

CHU Sainte-JustineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Oral acetaminophen arm

IV acetaminophen arm

Arm Description

they will receive oral acetaminophen, placebo (saline) IV

they will receive IV acetaminophen, placebo oral

Outcomes

Primary Outcome Measures

Change in pain scores

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

Quantity of rescue opioids (morphine equivalent in mg/kg) within the first 24 hours following initiation of study drug

Secondary Outcome Measures

Adverse events

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

Blood level of acetaminophen will be determined

Full Information

NCT ID

NCT05557344

First Posted

August 24, 2022

Last Updated

September 23, 2022

Sponsor

Dr. Niina Kleiber

1. Study Identification

Unique Protocol Identification Number

NCT05557344

Brief Title

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

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 21, 2021 (Actual)

Primary Completion Date

September 1, 2023 (Anticipated)

Study Completion Date

March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Dr. Niina Kleiber

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pain

Keywords

pain, analgesics, pediatrics, acetaminophen, orthopedics, pharmacokinetics

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Oral acetaminophen arm

Arm Type

Active Comparator

Arm Description

they will receive oral acetaminophen, placebo (saline) IV

Arm Title

IV acetaminophen arm

Arm Type

Active Comparator

Arm Description

they will receive IV acetaminophen, placebo oral

Intervention Type

Drug

Intervention Name(s)

Acetaminophen IV

Intervention Description

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

Intervention Name(s)

Acetaminophen

Intervention Description

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%.

Primary Outcome Measure Information:

Title

Change in pain scores

Description

Time Frame

During 24h (starting with the first dose of study drug)

Title

Difference in quantity of rescue opioids

Description

Quantity of rescue opioids (morphine equivalent in mg/kg) within the first 24 hours following initiation of study drug

Time Frame

During 24h (starting with the first dose of study drug)

Secondary Outcome Measure Information:

Title

Adverse events

Description

Time Frame

During 24h (starting with the first dose of study drug)

Title

Determination of oral bioavailability

Description

Blood level of acetaminophen will be determined

Time Frame

During 24 hours after the first dose of study drug

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Niina Kleiber, MD

Phone

(514) 3454931

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

First Name & Middle Initial & Last Name or Official Title & Degree

Evelyne Trottier

Phone

(514) 3454931

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Niina Kleiber, MD PhD

Organizational Affiliation

St. Justine's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU Sainte-Justine

City

Montréal

State/Province

Quebec

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Niina kleiber, MD

Phone

514 3454931

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

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34676011

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.

Results Reference

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Oral vs IV Acetaminophen for Long-bone Fracture in Children

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