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

Phase 3

Completed

Conditions: Acute Pain

Interventions: Drug: IV Acetaminophen
Drug: IV Control

Registration Number: NCT01635101

Lead Sponsor: Mallinckrodt

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 197

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High Dose Acetaminophen	IV Acetaminophen	Participants receive a low dose of acetaminophen (IV) for 24 hours
Placebo	IV Control	Participants receive matching placebo (IV) for 24 hours
Low Dose Acetaminophen	IV Acetaminophen	Participants receive a low dose of acetaminophen intravenously (IV) for 24 hours

Primary Outcome Measures

Name	Time	Method
Total Rescue Opioid Consumption	in 24 hours	Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication

Secondary Outcome Measures

Name	Time	Method
Summary of Pain Intensity Using the LNPS in Younger Infants	within 24 hours	The LNPS is used for assessing pain intensity in younger infants. Scores on the scale run from 0-14. Higher scores mean worse pain.
Pain Intensity Using the FLACC Score in Older Infants	within 24 hours	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.
Time to First Rescue Medication	within 24 hours
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates	within 24 Hours	The LNPS is used for assessing pain intensity in neonates. Scores on the scale run from 0-14. Higher scores mean worse pain.
Pain Intensity Using the FLACC Score in Intermediate Aged Infants	within 24 hours	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.

Trial Locations

Locations (22): Stanford University
🇺🇸
Stanford, California, United States
Amplatz Children's Hospital
🇺🇸
Minneapolis, Minnesota, United States
Penn State Milton S. Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Duke University
🇺🇸
Durham, North Carolina, United States
Children's Medical Center Dallas
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Dallas, Texas, United States
University of North Carolina-Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
The Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Univ. of Texas Health Sciences Center
🇺🇸
Houston, Texas, United States
Kings County Hospital Center
🇺🇸
Brooklyn, New York, United States
Monroe Carell Jr. Children's Hospital at Vanderbilt
🇺🇸
Nashville, Tennessee, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Rady Children's Hosptial San Diego
🇺🇸
San Diego, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸
Chicago, Illinois, United States
Jackson Memorial Hospital
🇺🇸
Miami, Florida, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Children's Hospital of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
Medical College of Wisconsin, Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States
Children's Of Alabama
🇺🇸
Birmingham, Alabama, United States