Clinical trial NCT01635101: A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Pain
Keywords: Moderate to severe acute pain following surgery or trauma
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2012-07-06
Enrollment: 197
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Total Rescue Opioid Consumption
timeFrame: in 24 hours
Secondary outcomes:
measure: Time to First Rescue Medication
timeFrame: within 24 hours
measure: Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
timeFrame: within 24 Hours
measure: Summary of Pain Intensity Using the LNPS in Younger Infants
timeFrame: within 24 hours
measure: Pain Intensity Using the FLACC Score in Intermediate Aged Infants
timeFrame: within 24 hours
measure: Pain Intensity Using the FLACC Score in Older Infants
timeFrame: within 24 hours
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Of Alabama
state: Alabama
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Rady Children's Hosptial San Diego
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Ann Arbor
country: United States
facility: Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Amplatz Children's Hospital
state: Minnesota
city: Brooklyn
country: United States
facility: Kings County Hospital Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina-Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: Univ. of Texas Health Sciences Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Mallinckrodt
name: Clinical Team Leader
role: STUDY_DIRECTOR
References:
citation: Hammer GB, Maxwell LG, Taicher BM, Visoiu M, Cooper DS, Szmuk P, Pheng LH, Gosselin NH, Lu J, Devarakonda K. Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants. J Clin Pharmacol. 2020 Jan;60(1):16-27. doi: 10.1002/jcph.1508. Epub 2019 Aug 25.