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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

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ClinicalTrials.gov Identifier: NCT01635101
Recruitment Status : Completed
First Posted : July 6, 2012
Last Update Posted : August 11, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
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

Study Design

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
Primary Completion Date : August 2015
Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

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


Eligibility Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT01635101


  Show 22 Study Locations
Sponsors and Collaborators
Mallinckrodt
Investigators
Study Director: Malcolm Lloyd-Smith, MS Mallinckrodt
More Information

Responsible Party: Mallinckrodt
ClinicalTrials.gov 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:
Acute Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics