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

Acute Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01635101
• Other study ID #: CPI-APA-353
• Status: Completed
• Phase: Phase 3
• Start date: June 2012
• Est. completion date: November 2015

Study information

• Verified date: May 2017
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: November 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain

Intervention

Drug:
• IV Acetaminophen
IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours
• IV Control
IV Control q6h; 4 doses, in 24 hours

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to First Rescue Medication		within 24 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	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