NCT01635101

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
197

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2012

Typical duration for phase_3

Geographic Reach
1 country

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2012

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

June 29, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 6, 2012

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2015

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

January 21, 2020

Completed
Last Updated

January 21, 2020

Status Verified

May 1, 2017

Enrollment Period

3.2 years

First QC Date

June 29, 2012

Results QC Date

September 10, 2019

Last Update Submit

January 10, 2020

Conditions

Keywords

Moderate to severe acute pain following surgery or trauma

Outcome Measures

Primary Outcomes (1)

  • Total Rescue Opioid Consumption

    Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication

    in 24 hours

Secondary Outcomes (5)

  • Time to First Rescue Medication

    within 24 hours

  • Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates

    within 24 Hours

  • Summary of Pain Intensity Using the LNPS in Younger Infants

    within 24 hours

  • Pain Intensity Using the FLACC Score in Intermediate Aged Infants

    within 24 hours

  • Pain Intensity Using the FLACC Score in Older Infants

    within 24 hours

Study Arms (3)

Low Dose Acetaminophen

EXPERIMENTAL

Participants receive a low dose of acetaminophen intravenously (IV) for 24 hours

Drug: IV Acetaminophen

High Dose Acetaminophen

EXPERIMENTAL

Participants receive a low dose of acetaminophen (IV) for 24 hours

Drug: IV Acetaminophen

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo (IV) for 24 hours

Drug: IV Control

Interventions

IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours

Also known as: OFIRMEV
High Dose AcetaminophenLow Dose Acetaminophen

IV Control q6h; 4 doses, in 24 hours

Also known as: Saline, Placebo
Placebo

Eligibility Criteria

Age1 Day - 2 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

Children's Of Alabama

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hosptial San Diego

San Diego, California, 92123, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33236, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Amplatz Children's Hospital

Minneapolis, Minnesota, 55455, United States

Location

Kings County Hospital Center

Brooklyn, New York, 11203, United States

Location

University of North Carolina-Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

Univ. of Texas Health Sciences Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin, Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

  • Hammer GB, Maxwell LG, Taicher BM, Visoiu M, Cooper DS, Szmuk P, Pheng LH, Gosselin NH, Lu J, Devarakonda K. Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants. J Clin Pharmacol. 2020 Jan;60(1):16-27. doi: 10.1002/jcph.1508. Epub 2019 Aug 25.

MeSH Terms

Conditions

Acute PainWounds and Injuries

Interventions

AcetaminophenSodium Chloride

Condition Hierarchy (Ancestors)

PainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Results Point of Contact

Title
Medical Information Call Center
Organization
Mallinckrodt

Study Officials

  • Clinical Team Leader

    Mallinckrodt

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 29, 2012

First Posted

July 6, 2012

Study Start

June 1, 2012

Primary Completion

August 1, 2015

Study Completion

November 1, 2015

Last Updated

January 21, 2020

Results First Posted

January 21, 2020

Record last verified: 2017-05

Data Sharing

IPD Sharing
Will not share

Locations