Acetaminophen IV for Pediatric Patients

Principal Investigator: Michael  Spigarelli
Keywords: Acetaminophen , Acute Pain , Pediatric , Intravenous , Neonates , Infants Department: Pediatric Administration
IRB Number: 00063368 Co Investigator: Robert DiGeronimo
Specialty: Pediatrics, General
Sub Specialties:
Recruitment Status: Not yet recruiting

Contact Information

Becky  Kinzel

Brief Summary

The purpose for the proposed study is to demonstrate efficacy and to provide additional PK/PD data to support evidence-based dosing recommendations for IV acetaminophen for the management of pain in pediatric patients under 2 years of age.

Primary Objective:


To demonstrate the efficacy of IV acetaminophen plus standard of care rescue opioids [SOC] (IV Acetaminophen Group) for the relief of moderate to severe acute pain in neonates and infants (age < 2 years) compared to placebo plus SOC (Control Group), as indicated by a reduction in opioid consumption


Secondary Objectives:


  • To characterize the concentration-effect relationship (pharmacokinetic/analgesic efficacy pharmacodynamics comparison [PK/PD comparison]) of the IV Acetaminophen Group vs. Control Group for the treatment of acute pain in pediatric inpatient subjects < 2 years of age
  • To characterize key acetaminophen PK parameters and explore the relationship of acetaminophen exposure to efficacy and safety


  • To demonstrate the efficacy of IV acetaminophen for the treatment of acute heel stick pain in pediatric inpatient subjects < 2 years of age


  • To collect additional safety data for IV acetaminophen in pediatric inpatient subjects < 2 years old

Inclusion Criteria

To be eligible for entry into the Study, Subjects must meet, or Subjects’ Parent or Guardian must

 meet, agree with, or confirm all of the following criteria:


  • Subject is ≥ 28 weeks to ≤ 40 weeks gestational age and < 2 years old at study


  • Subject will undergo surgery or had a traumatic injury expected to produce moderate to severe pain and patient is expected to require analgesia for acute pain for 24 hours


  • Subject has a medically reasonable need and expectation for IV treatment due to their underlying procedure(s) or medical condition(s) for the duration of the study


  • Subject has a bodyweight which, in the opinion of the Investigator does not preclude
    participation in the study.


  • Subject has reliable vascular access for administration of study medication and PK sampling


  • 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

Pre-Randomization (Qualification) Inclusion Criteria

To be eligible to be randomized into the study, subjects must meet the following criteria prior to
1. Subject has not been administered the following:
a. any acetaminophen-containing product, NSAIDs, central alpha-adrenergic agents
(e.g., clonidine, dexmedetomidine) or ketamine within 6 hours of T0
b. regional or neuraxial (caudal, epidural or spinal) anesthetic with local anesthetics
within 6 hours of T0
2. Subject does not have abnormal LFTs and/or liver enzymes from a sample obtained postoperatively/
post-trauma and prior to randomization above the following limits:
a. TBL > 3 X ULN, OR
b. ALT > 3 X ULN, OR
c. TBL > 2 X ULN) AND ALT > 3 X ULN, OR
d. If neonate, in the absence of intentional anticoagulation, INR > 1.5 X ULN or
PT > 1.5 X ULN
3. Subject does not have significantly impaired renal function or known significant renal
disease, which in the opinion of the Investigator would contraindicate study participation.
4. Subject had a pain assessment performed by qualified nursing, anesthesia or other clinical
or research staff documenting moderate to severe pain (i.e., pain score of at least 4 on the
LNPS or FLACC, or moderate to severe pain using the institution’s preferred validated
observational pain scale) within 6 hours prior to randomization
5. Subject required at least one dose of parenteral opioid for pain management (i.e., not preemptive
therapy) during the 6-hour pre-randomization period, and is anticipated to
require at least one dose of parenteral opioid during the 24-hour treatment period.
6. If subject is breast feeding, mother has not been administered any acetaminophen-containing
product in the previous 6 hours prior to T0 and throughout the treatment

Exclusion Criteria

A subject is NOT eligible for entry into the study if ANY of the following criteria are met:


  • 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