A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy and safety of Intravenous (IV) acetaminophen plus rescue opioids for the relief of moderate to severe acute pain in neonates and infants (age < 2 years) compared to placebo plus standard of care rescue opioids as well as characterize the concentration-effect relationship (PK/PD) of the intravenous acetaminophen as compared to the control group.

Official Title
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A Randomized, Placebo Controlled, Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: IV Acetaminophen
* Drug: IV Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 28 weeks gestational age and < 2 years old at study enrollment Subject will undergo surgery or had a traumatic injury expected to produce moderate to severe pain and patient is expected to require analgesic treatment for acute pain for 24 hours Subject has a medically reasonable need for IV treatment due to their underlying procedure(s) or medical condition(s) for the duration of the study Subject has reliable vascular access for administration of study medication and PK sampling Subject has a bodyweight which, in the opinion of the Investigator does not preclude participation in the study. Subject is free of other physical, mental, or medical conditions which, in the opinion of the Investigator, make study participation inadvisable or make it impossible to accurately assess efficacy or safety endpoints Subject's parent or guardian must provide written informed consent prior to participation in the study Subject's parent or guardian must have the ability to read and understand the study procedures and have the ability to communicate meaningfully with the study investigator and staff Exclusion Criteria: Subject is not able to comply with the sampling requirements of the study Subject has known or suspected hypersensitivity to acetaminophen or the excipients of IV acetaminophen Subject has any significant medical condition that in the opinion of the Investigator contraindicates participation in the study or impairs the assessment of efficacy or safety Subject has participated in another interventional clinical study within 30 days of the planned study randomization date Pre-Randomization (Qualification) Inclusion Criteria Subject has not been administered any of the following: any acetaminophen-containing product, nonsteroidal anti-inflammatory agent, central alpha-adrenergic agents (e.g., clonidine, dexmedetomidine) or ketamine within 6 hours of baseline (T0) received a regional or neuraxial (caudal, epidural or spinal) anesthetic with local anesthetics within 6 hours of T0 Subject does not have abnormal liver function tests from a sample obtained post-operatively/post-trauma and prior to randomization above protocol-specified limits Subject does not have significantly impaired renal function or known significant renal disease which in the opinion of the Investigator would contraindicate study participation. Subject had a nursing assessment documenting moderate to severe pain within 6 hours prior to randomization Subject required at least one dose of parenteral opioid medication for pain management (i.e., not pre-emptive therapy) during the 6-hour pre-randomization period, and is anticipated to require at least one dose of parenteral opioid medication during the 24 hour treatment period If subject is breast feeding, mother has not been administered any acetaminophen containing product in the previous 6 hours to T0 and throughout the treatment period

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Acetaminophen<br>Participants receive a low dose of acetaminophen intravenously (IV) for 24 hours | Drug: IV Acetaminophen<br>* IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours<br>* Other names: OFIRMEV;|
| Experimental: High Dose Acetaminophen<br>Participants receive a low dose of acetaminophen (IV) for 24 hours | Drug: IV Acetaminophen<br>* IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours<br>* Other names: OFIRMEV;|
| Placebo Comparator: Placebo<br>Participants receive matching placebo (IV) for 24 hours | Drug: IV Control<br>* IV Control q6h; 4 doses, in 24 hours<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Rescue Opioid Consumption | Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication | in 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Rescue Medication |  | within 24 hours | 
| Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates | The LNPS is used for assessing pain intensity in neonates. Scores on the scale run from 0-14. Higher scores mean worse pain. | within 24 Hours | 
| Summary of Pain Intensity Using the LNPS in Younger Infants | The LNPS is used for assessing pain intensity in younger infants. Scores on the scale run from 0-14. Higher scores mean worse pain. | within 24 hours | 
| Pain Intensity Using the FLACC Score in Intermediate Aged Infants | The Face, Leg, Activity, Cry, and Consolability (FLACC) scale is used to assess pain intensity in intermediate aged infants. The scale is scored in a range of 0-10 with 0 representing no pain. A higher score means more pain. | within 24 hours | 
| Pain Intensity Using the FLACC Score in Older Infants | The FLACC scale is used to assess pain intensity in older infants. The scale is scored in a range of 0-10 with 0 representing no pain. A higher score means more pain. | within 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to severe acute pain following surgery or trauma