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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.
 
ClinicalTrials.gov Identifier: NCT01635101
Recruitment Status : Completed
First Posted : July 6, 2012
Results First Posted : January 21, 2020
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

Tracking Information
First Submitted Date  ICMJE June 29, 2012
First Posted Date  ICMJE July 6, 2012
Results First Submitted Date  ICMJE September 10, 2019
Results First Posted Date  ICMJE January 21, 2020
Last Update Posted Date January 21, 2020
Study Start Date  ICMJE June 2012
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
Total Rescue Opioid Consumption [ Time Frame: in 24 hours ]
Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication
Original Primary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
Total Rescue Opioid Consumption [ Time Frame: T0-T24; A total opiod 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Time to First Rescue Medication [ Time Frame: within 24 hours ]
  • Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates [ Time Frame: within 24 Hours ]
    The LNPS is used for assessing pain intensity in neonates. Scores on the scale run from 0-14. Higher scores mean worse pain.
  • Summary of Pain Intensity Using the LNPS in Younger Infants [ Time Frame: within 24 hours ]
    The LNPS is used for assessing pain intensity in younger infants. Scores on the scale run from 0-14. Higher scores mean worse pain.
  • Pain Intensity Using the FLACC Score in Intermediate Aged Infants [ Time Frame: within 24 hours ]
    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.
  • Pain Intensity Using the FLACC Score in Older Infants [ Time Frame: within 24 hours ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
  • 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.
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Acute Pain
Intervention  ICMJE
  • Drug: IV Acetaminophen
    IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours
    Other Name: OFIRMEV
  • Drug: IV Control
    IV Control q6h; 4 doses, in 24 hours
    Other Names:
    • Saline
    • Placebo
Study Arms  ICMJE
  • Experimental: Low Dose Acetaminophen
    Participants receive a low dose of acetaminophen intravenously (IV) for 24 hours
    Intervention: Drug: IV Acetaminophen
  • Experimental: High Dose Acetaminophen
    Participants receive a low dose of acetaminophen (IV) for 24 hours
    Intervention: Drug: IV Acetaminophen
  • Placebo Comparator: Placebo
    Participants receive matching placebo (IV) for 24 hours
    Intervention: Drug: IV Control
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2020)
197
Original Estimated Enrollment  ICMJE
 (submitted: July 5, 2012)
200
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 2 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01635101
Other Study ID Numbers  ICMJE CPI-APA-353
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mallinckrodt
Study Sponsor  ICMJE Mallinckrodt
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Team Leader Mallinckrodt
PRS Account Mallinckrodt
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP