Acute PainPhase 3NCT01635101

A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients

A Phase 3 study testing IV Acetaminophen in people with Acute Pain, run by Mallinckrodt at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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… Read more about this study

Who is it for?: Ages 1 day to 2 years
Conditions the study is for: Acute Pain
What is being tested?: IV Acetaminophen
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 197 participants
Where: 22 sitesUnited States
Study dates: Jun 2012to Nov 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 day to 2 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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:

Show all 13Show fewer

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

Trial locations and contacts

22 sites in 1 country.

City, postcode or hospital

22 sites in 1 country

United States22 sites

Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Of Alabama
Birmingham, Alabama, 35294
Kings County Hospital Center
Brooklyn, New York, 11203
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina, 27599
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Medical Center Dallas
Dallas, Texas, 75235
Duke University
Durham, North Carolina, 27710
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Univ. of Texas Health Sciences Center
Houston, Texas, 77030
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Louisville
Louisville, Kentucky, 40202
Jackson Memorial Hospital
Miami, Florida, 33236
Medical College of Wisconsin, Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Amplatz Children's Hospital
Minneapolis, Minnesota, 55455
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Children's Hospital of Orange County
Orange, California, 92868
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Virginia Commonwealth University
Richmond, Virginia, 23298
Rady Children's Hosptial San Diego
San Diego, California, 92123
Stanford University
Stanford, California, 94305

Other trials in United States

About this study

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

Conditions: Acute Pain
Being tested: IV Acetaminophen, IV Control
Keywords: Moderate to severe acute pain following surgery or trauma
Medical subject headings: Acute Pain, Wounds and Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IV AcetaminophenDrug
Also called OFIRMEV
IV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours
IV ControlDrug
Also called Saline, Placebo
IV Control q6h; 4 doses, in 24 hours

Study groups in NCT01635101
Study group	Role	What they receive
Low Dose Acetaminophen	Experimental	Participants receive a low dose of acetaminophen intravenously (IV) for 24 hours Receives: Drug: IV Acetaminophen
High Dose Acetaminophen	Experimental	Participants receive a low dose of acetaminophen (IV) for 24 hours Receives: Drug: IV Acetaminophen
Placebo	Placebo comparator	Participants receive matching placebo (IV) for 24 hours Receives: Drug: IV Control

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: in 24 hours

Secondary outcomes (5)

Time to First Rescue Medication
Measured: within 24 hours
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
The LNPS is used for assessing pain intensity in neonates. Scores on the scale run from 0-14. Higher scores mean worse pain.
Measured: within 24 Hours
Summary of Pain Intensity Using the LNPS in Younger Infants
The LNPS is used for assessing pain intensity in younger infants. Scores on the scale run from 0-14. Higher scores mean worse pain.
Measured: within 24 hours
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
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.
Measured: within 24 hours
Pain Intensity Using the FLACC Score in Older Infants
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.
Measured: within 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Nov 2015

First posted6 Jul 2012 (estimated)
Study startJun 2012
Primary completionAug 2015
Study completionNov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute PainStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 197 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01635101
Sponsor's protocol ID: CPI-APA-353
Status last verified: May 2017
First submitted: 29 Jun 2012
Last updated: 21 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

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.
PubMed 31448420

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruitingPhase 2
A Clinical Trial of MK-6916 in Participants With Pain After Bunion Removal Surgery (MK-6916-007)
Pain Management
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)

All Acute Pain trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01635101
Acronym / sponsor ID: CPI-APA-353
Conditions: Acute Pain
Keywords: Moderate to severe acute pain following surgery or trauma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 197 participants (actual)
Lead sponsor: MallinckrodtIndustry (pharma, biotech, devices)
Study start: Jun 2012
Primary completion: Aug 2015 (actual)
Study completion: Nov 2015 (actual)
First posted: 6 Jul 2012 (estimated)
Results: Posted 21 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Low Dose Acetaminophen	Experimental	Drug: IV AcetaminophenParticipants receive a low dose of acetaminophen intravenously (IV) for 24 hours
High Dose Acetaminophen	Experimental	Drug: IV AcetaminophenParticipants receive a low dose of acetaminophen (IV) for 24 hours
Placebo	Placebo comparator	Drug: IV ControlParticipants receive matching placebo (IV) for 24 hours

Who may qualify

Ages: 1 day to 2 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IV AcetaminophenAlso: OFIRMEVIV Acetaminophen given every 6 hours (q6h); 4 doses, in 24 hours	Drug	High Dose Acetaminophen, Low Dose Acetaminophen
IV ControlAlso: Saline, PlaceboIV Control q6h; 4 doses, in 24 hours	Drug	Placebo

Primary outcome

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

5 secondary outcomes

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
Summary of Pain Intensity Using the LNPS in Younger Infants
Time frame: within 24 hours
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
Time frame: within 24 hours
Pain Intensity Using the FLACC Score in Older Infants
Time frame: within 24 hours

Results and safety

Results posted to the registry on 21 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low Dose Acetaminophen	61	52
High Dose Acetaminophen	67	55
Placebo	69	52

Primary outcome: Total Rescue Opioid Consumption

Time frame: in 24 hours. Mean (Standard Deviation). Unit: µg/kg

Measure	Low Dose Acetaminophen n = 61	High Dose Acetaminophen n = 67	Placebo n = 69
Value	166.9 (225.06)	179.9 (193.47)	180.2 (184.70)

Low Dose Acetaminophen vs Placebo: LS Mean Difference: -11.8 (97.5% CI -91.0 to 67.3), p = 0.736, ANOVA
High Dose Acetaminophen vs Placebo: LS Mean Difference: 1.4 (97.5% CI -75.9 to 78.7), p = 0.967, ANOVA

Population analysed: mITT population

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 hours. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Low Dose Acetaminophen	0 of 61 (0%)	21 of 61 (34.4%)	0 of 61
High Dose Acetaminophen	1 of 67 (1.5%)	8 of 67 (11.9%)	0 of 67
Placebo	2 of 69 (2.9%)	24 of 69 (34.8%)	0 of 69

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31448420Hammer 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.
Individual participant dataSharing planned: No

Related trials for Acute Pain

Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruitingPhase 2
A Clinical Trial of MK-6916 in Participants With Pain After Bunion Removal Surgery (MK-6916-007)
Pain Management
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Team Leader study director

Mallinckrodt

22 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IV Acetaminophen in people with Acute Pain, run by Mallinckrodt at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Rescue Opioid Consumption (time frame: in 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01635101, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2020.