Ibuprofen Plus Acetaminophen for Enhanced Pain Reduction
Primary Purpose
Pain, Acute
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ibuprofen
Acetaminophen
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pain, Acute focused on measuring children
Eligibility Criteria
Inclusion Criteria:
- Patients with a numeric pain score of greater than or equal to 5 or Wong -Baker FACES Pain Scale of greater than or equal to 6
Exclusion Criteria:
- known allergy to ibuprofen
- Known allergy to acetaminophen
- documented or suspected pregnancy
- inability to tolerate oral medication
- a contraindication to oral intake
- inability to reliably indicate a pain score
- intake of ibuprofen or acetaminophen less than 4 hours prior to presentation
- inability to communicate in Spanish or English
- the need for immediate parenteral pain medication as per the treating physician.
Sites / Locations
- Jacobi Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Intervention group
Placebo Group
Arm Description
Intervention Group: ibuprofen 10 mg/kg (maximum 600mg) plus acetaminophen 15mg/kg (maximum 650mg)
Placebo Group: Ibuprofen 10mg/kg (maximum 600 mg) plus placebo 15mg/kg (maximum 650mg)
Outcomes
Primary Outcome Measures
Pain score
Change in mean pain score from baseline pain score. A validated pain score for children beginning at 3 years old, the Wong-Baker FACES pain scale (0-10 scale), will be used for patients ages 3 through 7 years. A validated numeric pain score (0-10 scale) will be used for patients 8 through 20 years. The higher score indicate worse pain.
Secondary Outcome Measures
Number of participants requiring rescue medications.
Documentation of the need for rescue medications (number and dose)
Full Information
NCT ID
NCT04630834
First Posted
November 11, 2020
Last Updated
April 7, 2022
Sponsor
New York City Health and Hospitals Corporation
1. Study Identification
Unique Protocol Identification Number
NCT04630834
Brief Title
Ibuprofen Plus Acetaminophen for Enhanced Pain Reduction
Official Title
Oral Ibuprofen Plus Acetaminophen Versus Ibuprofen Alone for Acute Pain Reduction in Children
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 30, 2021 (Actual)
Primary Completion Date
June 20, 2022 (Anticipated)
Study Completion Date
June 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York City Health and Hospitals Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Combination of analgesics with different modes of action have the potential to offer enhanced pain relief with reduced dosage. Ibuprofen and acetaminophen have different modes of action. Combination of ibuprofen and acetaminophen has shown enhanced analgesia in adult studies, with pediatric data limited to post-operative pain and dental pain. Our study objective is to evaluate the analgesic efficacy of oral acetaminophen plus ibuprofen versus ibuprofen plus placebo for the management of acute pain in a pediatric emergency department.
Detailed Description
In the pediatric emergency department (PED), acute traumatic and nontraumatic pain accounts for approximately 9% of ED visits. The initial drugs of choice for analgesia are typically ibuprofen or acetaminophen. Both drugs display analgesic and antipyretic effects via distinct mechanisms of action. Various meta-analyses in the literature have compared ibuprofen and acetaminophen for pain relief in adults and children. Ibuprofen has been shown to be very effective for mild to moderate pain, especially in musculoskeletal injuries, including some limb fractures.
Combination of analgesics with different modes of action have the potential to offer enhanced pain relief with reduced dosage. Ibuprofen and acetaminophen have different modes of action. Ibuprofen is an NSAID that inhibits the activity of cyclooxygenase-1 and cyclooxygenase-2 enzymes and blocks the synthesis of prostaglandins and thromboxanes. The mode of action of acetaminophen for its analgesic effects is not entirely understood. It is thought that its effects are mediated through serotonergic pathways, cannabinoid and nitric oxide synthase, substance P, and N-methyl-D-aspartate. Combination of ibuprofen and acetaminophen has shown enhanced analgesia in adult studies, with pediatric data limited to post-operative pain and dental pain.
The data is limited regarding the combination of acetaminophen and ibuprofen for acute pain in the PED. A recent study showed similar analgesic efficacy of oral ibuprofen and acetaminophen in comparison with each analgesic alone for short-term treatment of acute pain in the PED7. In this study, pain reassessment was limited to only one time point at 60 minutes and included patients with pain scores of 1 on a 10 point scale. Since there is ample data demonstrating the effectiveness of ibuprofen for pain, we will investigate whether the combination of ibuprofen plus acetaminophen is superior for moderate to severe pain reduction compared to ibuprofen alone.
Objective To evaluate the analgesic efficacy of oral acetaminophen plus ibuprofen versus ibuprofen plus placeboalone for the management of acute pain in a pediatric emergency department.
Hypothesis: The combination of oral acetaminophen and ibuprofen is superior to ibuprofen alone for the reduction of acute traumatic and nontraumatic pain.
Study Design This will be a prospective, double-blind, placebo-controlled randomized trial, conducted in the pediatric emergency department.
Participant Recruitment Patients ages 3 years through 20 years who present to the PED with traumatic and/or nontraumatic pain will be assessed for eligibility. Pain assessment will be performed by a study investigator upon presentation at triage before medication administration. A validated numeric pain score (11-point 0-10 scale) will be used for patients 8 through 20 years. The Wong-Baker FACES Pain Scale (11-point 0-10 scale) will be used for patients ages 3 through 7 years. If the patient is eligible for enrollment, details of the study will be discussed with parent and/or patient and consent/assent will be obtained if they agree to participate.
Female patients >12 years will be assessed for pregnancy with a point of care urine HCG test. Pregnant patients will be excluded. Patients found to be pregnant will not be enrolled in the study and will be given appropriate care as is our standard procedure.
Study Intervention Study participants will be randomized to one of two treatment groups according to predetermined block randomization. A clinical research pharmacist will prepare placebo and acetaminophen in identical 20 mL amber bottles labeled sequentially. The bottle, 5, 10 and 20 mL amber syringes, and study documents will be stored in individual sequentially numbered manilla envelopes in a locked cabinet in the PED medication room. A nurse will draw the appropriate weight-based dose of placebo or medication into the amber syringes and administer the placebo or medication to the patient. Additionally, the nurse will administer a weight based dose of ibuprofen to each study participant.
The placebo group will receive a single weight-based dose of oral ibuprofen (100mg/5mL) at 10mg/kg to a maximum of 600 mg and placebo, mirrored as acetaminophen concentration of 160mg/5mL, at 15mg/kg to a maximum of 20 mL. The intervention group will receive a weight-based dose of ibuprofen (100mg/5mL) at 10mg/kg to a maximum of 600 mg and a dose of acetaminophen (160mg/5mL) at 15mg/kg to a maximum of 20 mL (650mg). The patient will then be evaluated in a standard manner by a treating clinician. The study investigator will reassess the pain score at 1 hour and 2 hours after medication administration. At the discretion of the treating physician, patients will receive parenteral medications at any time during the two hour assessment period for increasing or unremitting pain. Patients who are ready for discharge before the two hour pain assessment will receive a final pain score by the study investigator with documentation of time of the reassessment. Adverse events during the assessment period will be documented on a data collection sheet.
Subject treatment assignments will remain blinded until the final subject has completed follow up and all data has been recorded and validated. Urgent, immediate unblinding due to medical emergency may be authorized by the Investigator. When possible, the treatment assignment will be provided to the treating physician in order to maintain the blind for the Investigator and study staff. All instances of subject unblinding will be documented in the study record
Consent Written informed consent will be obtained by a study investigator at triage before initiation of treatment. An informed consent will be obtained parent or legal guardian for all patients 17 years and younger. Patients ages 13 years and older will sign an informed consent and an assent will be obtained from patients 7 years to 12 years of age.
Patients who are in pain and are first approached at the time the protocol will be initiated must be capable of providing contemporaneous informed consent. The principal investigator or study investigator will assess the capacity of the patient to provide ethically adequate informed consent. If the patient has capacity and consents to participation these facts will be documented in the patient's research record.
Confidentiality All patient data and research records will be kept confidential. Data collection sheets will be stored in a locked cabinet in the principal investigator's locked office throughout the study period and will be accessible only to research staff. Data will be collected on paper forms then entered into a password protected computer database. After data collection is performed, identifiers will be removed from the data file. Research investigators responsible for study collection, nurses, study participants and clinicians providing care to the patient in the emergency department will be blinded to the medication received.
Benefits The potential benefit of combined acetaminophen and ibuprofen therapy may provide an increased reduction in acute pain, improved patient comfort and patient/parent satisfaction compared to ibuprofen administered as a single agent. Enhanced pain reduction may potentially obviate the need for parenteral pain medication, including opioids. An additional benefit is the opportunity to contribute to research regarding pain management in children.
Risks This study may involve slightly more than minimal risk. Risk of participation in this study may be failure of combination therapy to potentiate pain reduction. Since patients will be randomized into treatment or placebo groups, they will not have the ability to choose a treatment option. Acetaminophen can be given at any age, however, there is a risk of liver toxicity in overdose. Ibuprofen has common side effects of gastrointestinal and renal effects including gastric irritation and acute renal injury. These risks, however, are considered to be minimal the medications are given as a single weight-based dose.
Data Analysis Baseline and post-treatment pain scores at 1 and 2 hours will be documented. Categorical data will be compared using the chi-squared test. Continuous data will be compared using the Mann-Whitney test for non-normally distributed data and t-test for normally distributed data. For our sample size calculation, we made the following assumptions: previous studies investigating pain scores in children have reported a decrease in pain score of 1 on a 10-point scale to be clinically significant. For this study, we assumed that a decrease in pain score of 2 would be clinically relevant. We used a standard deviation of 3 for our sample size calculation. We also assumed a 20% dropout rate and increased our sample size estimate by 15% to account for nonparametric data. Based on these assumptions, for our primary outcome, we estimated 50 patients would be needed in each group to have a power of 80% with an alpha of 0.05 to detect a difference of 2 in pain score between the two groups, with a standard deviation of 3. Data analyses of the pain scores will be based on the principle of intention to treat.
Data Safety Monitoring Plan
This is a single site study involving a biochemical intervention that presents slightly more than minimal risk due potential adverse effects from medication and randomized design. Close-monitoring will be performed by the study investigator and co-investigator every other month, or every 20 patients enrolled, whichever is more frequent. The specific procedures that will be used to monitor for and report adverse events, protocol violations and deviations are:
Data will be analyzed for participant recruitment
Data quality and protocol adherence, as determined by completeness of forms
Protocol adherence as determined by times of drug administration and pain assessments
Quality of informed consent process and documentation as determined by review of all forms for valid signatures and times
Analysis of adverse effects of medication determined by rates of such events as identified on data collection forms
The Data Safety Monitoring Committee Members will be:
Anthony Ciorciari, MD - Department of Emergency Medicine Michael Jones, MD - Department of Emergency Medicine Jackeline Urrutia-Monteleone, MD - Department of Pediatrics
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Acute
Keywords
children
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Two arms will be run in parallel. One arm will be acetaminophen and ibuprofen combined. The other arm will be ibuprofen alone with a placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention group
Arm Type
Active Comparator
Arm Description
Intervention Group: ibuprofen 10 mg/kg (maximum 600mg) plus acetaminophen 15mg/kg (maximum 650mg)
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Placebo Group: Ibuprofen 10mg/kg (maximum 600 mg) plus placebo 15mg/kg (maximum 650mg)
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Intervention Description
Patients will receive both ibuprofen 10mg/kg weight based dosing with a max of 600mg
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Description
patients will receive acetaminophen 15 mg/kg weight based dosing with a max of 650mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
patients will receive placebo 15mg/kg weight based dosing with a max of 650mg
Primary Outcome Measure Information:
Title
Pain score
Description
Change in mean pain score from baseline pain score. A validated pain score for children beginning at 3 years old, the Wong-Baker FACES pain scale (0-10 scale), will be used for patients ages 3 through 7 years. A validated numeric pain score (0-10 scale) will be used for patients 8 through 20 years. The higher score indicate worse pain.
Time Frame
1 hour and 2 hours
Secondary Outcome Measure Information:
Title
Number of participants requiring rescue medications.
Description
Documentation of the need for rescue medications (number and dose)
Time Frame
1 hour and 2 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patients with a numeric pain score of greater than or equal to 5 or Wong -Baker FACES Pain Scale of greater than or equal to 6
Exclusion Criteria:
known allergy to ibuprofen
Known allergy to acetaminophen
documented or suspected pregnancy
inability to tolerate oral medication
a contraindication to oral intake
inability to reliably indicate a pain score
intake of ibuprofen or acetaminophen less than 4 hours prior to presentation
inability to communicate in Spanish or English
the need for immediate parenteral pain medication as per the treating physician.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra Cunningham, MD
Phone
718-918-5875
Email
sandra.cunningham@nychhc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Jackeline Urrutia-Monteleone, MD
Phone
718-918-5875
Email
urrutiaj@nychhc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandra Cunningham, MD
Organizational Affiliation
NYCHHC - Jacobi Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jacobi Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra Cunningham, MD
Phone
718-918-5875
Email
sandra.cunningham@nbhn.net
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29912084
Citation
Poddighe D, Brambilla I, Licari A, Marseglia GL. Ibuprofen for Pain Control in Children: New Value for an Old Molecule. Pediatr Emerg Care. 2019 Jun;35(6):448-453. doi: 10.1097/PEC.0000000000001505.
Results Reference
background
PubMed Identifier
29622325
Citation
Gaglani A, Gross T. Pediatric Pain Management. Emerg Med Clin North Am. 2018 May;36(2):323-334. doi: 10.1016/j.emc.2017.12.002.
Results Reference
background
PubMed Identifier
24779190
Citation
Jozwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014 Jan-Feb;71(1):11-23.
Results Reference
background
PubMed Identifier
20142348
Citation
Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010 Apr 1;110(4):1170-9. doi: 10.1213/ANE.0b013e3181cf9281. Epub 2010 Feb 8.
Results Reference
background
PubMed Identifier
17397460
Citation
Gazal G, Mackie IC. A comparison of paracetamol, ibuprofen or their combination for pain relief following extractions in children under general anaesthesia: a randomized controlled trial. Int J Paediatr Dent. 2007 May;17(3):169-77. doi: 10.1111/j.1365-263X.2006.00806.x.
Results Reference
background
PubMed Identifier
32247660
Citation
Motov S, Butt M, Masoudi A, Palacios W, Fassassi C, Drapkin J, Likourezos A, Hossain R, Brady J, Rothberger N, Flom P, Zerzan J, Marshall J. Comparison of Oral Ibuprofen and Acetaminophen with Either Analgesic Alone for Pediatric Emergency Department Patients with Acute Pain. J Emerg Med. 2020 May;58(5):725-732. doi: 10.1016/j.jemermed.2020.02.010. Epub 2020 Apr 1.
Results Reference
background
Links:
URL
http://www.cdc.gov/nchs/data/nhamcs/webtables/2017edwebtables-508.pdf
Description
Ntional Hospital Ambulatory Medical Care Survey: 2017 emergency department summary tables
Learn more about this trial
Ibuprofen Plus Acetaminophen for Enhanced Pain Reduction
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