A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients
Condition: Acute Pain
MeSH terms: Acute Pain
Intervention: IV Acetaminophen; IV Control
Intervention description: IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours; IV Control q6h; 4 doses, in 24 hours
Intervention MeSH terms: Acetaminophen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 197.0
Sex: All
Minimum age: 1 Day
Maximum age: 2 Years
Healthy volunteers: No
Keywords: Moderate to severe acute pain following surgery or trauma

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.
    

Eligibility 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

          -  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