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

NCT ID: NCT01635101

Last Updated: 2020-01-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2015-11-30

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.

Detailed Description

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Conditions

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Acute Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Low Dose Acetaminophen

Participants receive a low dose of acetaminophen intravenously (IV) for 24 hours

Group Type EXPERIMENTAL

IV Acetaminophen

Intervention Type DRUG

IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours

High Dose Acetaminophen

Participants receive a low dose of acetaminophen (IV) for 24 hours

Group Type EXPERIMENTAL

IV Acetaminophen

Intervention Type DRUG

IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours

Placebo

Participants receive matching placebo (IV) for 24 hours

Group Type PLACEBO_COMPARATOR

IV Control

Intervention Type DRUG

IV Control q6h; 4 doses, in 24 hours

Interventions

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IV Acetaminophen

IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours

Intervention Type DRUG

IV Control

IV Control q6h; 4 doses, in 24 hours

Intervention Type DRUG

Other Intervention Names

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OFIRMEV Saline Placebo

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


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

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
Minimum Eligible Age

1 Day

Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mallinckrodt

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Team Leader

Role: STUDY_DIRECTOR

Mallinckrodt

Locations

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Children's Of Alabama

Birmingham, Alabama, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Rady Children's Hosptial San Diego

San Diego, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Jackson Memorial Hospital

Miami, Florida, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Amplatz Children's Hospital

Minneapolis, Minnesota, United States

Site Status

Kings County Hospital Center

Brooklyn, New York, United States

Site Status

University of North Carolina-Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Site Status

Children's Medical Center Dallas

Dallas, Texas, United States

Site Status

Univ. of Texas Health Sciences Center

Houston, Texas, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Medical College of Wisconsin, Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 31448420 (View on PubMed)

Other Identifiers

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CPI-APA-353

Identifier Type: -

Identifier Source: org_study_id

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