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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01635101
Recruitment Status : Completed
First Posted : July 6, 2012
Last Update Posted : August 11, 2016
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Acute Pain Drug: IV Acetaminophen Other: Normal Saline as Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 215 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : June 2012
Actual Primary Completion Date : August 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: IV Acetaminophen
IV acetaminophen
Drug: IV Acetaminophen

7.5 mg/kg IV over 15 minutes, given q6h X 4 doses for 24 hours;

10 mg/kg IV over 15 minutes, given q6h X 4 doses for 24 hours;

12.5 mg/kg IV over 15 minutes, given q6h X 4 doses for 24 hours;

15 mg/kg IV over 15 minutes, given q6h X 4 doses for 24 hours

Other Name: Brand Name: OFIRMEV

Placebo Comparator: Normal Saline
Placebo saline
Other: Normal Saline as Placebo

Primary Outcome Measures :
  1. Total rescue opioid consumption [ Time Frame: T0-T24; A total opioid consumption will be obtained from T0-T24. Total rescue opioid consumption will be collected during the 24 hours while the subject is on study medication. ]
    Total rescue opioid consumption from T0 to T24 (total milligrams (mg) per kilogram (kg) IV morphine equivalent), comparing each IV Acetaminophen Group to the combined Control Groups

Secondary Outcome Measures :
  1. Correlation between efficacy concentration and rescue medication consumption. [ Time Frame: T0 to T12 FLAAC or LNPS will be assessed at T0, T0.05, T1, T2, T3, T4, T6, T12, T18, T24 and prior to each dose of rescue medication ]
    Correlation between efficacy concentration Ceff and total opioid rescue medication consumption (in IV morphine equianalgesic dose equivalents) from T0 to T12 comparing each IV Acetaminophen Group to the combined Control Groups. The correlation will be measured by the mean slope of the linear regression comparing acetaminophen exposure area under the curve (AUC) in the effect compartment and total milligrams (mg)/kilogram (kg) IV morphine equivalent doses from T0 to T12.

  2. Subjects with clinically meaningful changes in laboratory parameters [ Time Frame: T0-T24 Baseline labs as compared to End of Study Labs. Subject will be followed for an average of 24 hours while hospitalized. ]
    The percentage of subjects with clinically meaningful changes in laboratory parameters will be summarized by treatment group

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Ages Eligible for Study:   up to 2 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (for example, neurologic diseases such as hemiplegia, demyelinating disorders, or neuromuscular paralysis, or requirement for prolonged mechanical ventilation making it impossible to assess pain scales using the LNPS or the FLACC)
  • 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 T0
  • received a regional or neuraxial (caudal, epidural or spinal) anesthetic with local anesthetics within 6 hours of T0
  • Subject does not have abnormal LFTs from a sample obtained post-operatively/post-trauma and prior to randomization above the following limits:

    • TBL > 3 times upper limit of normal range for age, OR
    • ALT (SGPT) > 3 X ULN, OR
    • If neonate, in the absence of intentional anticoagulation, INR > 1.5 X ULN or PT > 1.5 X ULN
  • 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 (pain intensity score of at least 4 on the LNPS or FLACC) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01635101

  Hide Study Locations
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United States, Alabama
Children's Of Alabama
Birmingham, Alabama, United States, 35294
United States, California
Children's Hospital of Orange County
Orange County, California, United States, 92868
Rady Children's Hosptial San Diego
San Diego, California, United States, 92123
Stanford University
Stanford, California, United States, 94305
United States, Florida
Jackson Memorial Hospital
Miami, Florida, United States, 33236
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Michigan
Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Amplatz Children's Hospital
Minneapolis, Minnesota, United States, 55455
United States, New York
Kings County Hospital Center
Brooklyn, New York, United States, 11203
United States, North Carolina
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, United States, 37232
United States, Texas
Children's Medical Center Dallas
Dallas, Texas, United States, 75235
Univ. of Texas Health Sciences Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Wisconsin
Medical College of Wisconsin, Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
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Study Director: Malcolm Lloyd-Smith, MS Mallinckrodt

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Responsible Party: Mallinckrodt Identifier: NCT01635101     History of Changes
Other Study ID Numbers: CPI-APA-353
First Posted: July 6, 2012    Key Record Dates
Last Update Posted: August 11, 2016
Last Verified: August 2016
Keywords provided by Mallinckrodt:
Moderate to severe acute pain following surgery or trauma
Additional relevant MeSH terms:
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Acute Pain
Neurologic Manifestations
Signs and Symptoms
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs