Comparing Five Oral Analgesics for Treatment of Acute Pain in the Emergency Department (ED)

Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department

This study compares the efficacy of five oral analgesics: 5 mg oxycodone + 325 mg acetaminophen, 5 mg hydrocodone + 300 mg acetaminophen, 30 mg codeine + 300 mg acetaminophen, 400 mg ibuprofen + 1000 mg acetaminophen, and 800 mg ibuprofen + 1000 mg acetaminophen for the treatment of patients with acute musculoskeletal pain who present to the Emergency Department (ED).

Study Overview

• Status: Completed
• Conditions: Musculoskeletal Pain
• Intervention / Treatment: Drug: oxycodone/APAP; Drug: hydrocodone/APAP; Drug: codeine/APAP; Drug: 400 ibuprofen/APAP; Drug: 800 ibuprofen/APAP

Detailed Description

The optimal treatment of musculoskeletal extremity pain in the ED not known. The study is a randomized controlled trial designed to compare the efficacy of five oral analgesics: 5 mg oxycodone + 325 mg acetaminophen, 5 mg hydrocodone + 300 mg acetaminophen, 30 mg codeine + 300 mg acetaminophen, 400 mg ibuprofen + 1000 mg acetaminophen, and 800 mg ibuprofen + 1000 mg acetaminophen for the treatment of patients with acute musculoskeletal pain. The primary outcome is the between treatment group difference in change in patients' rating of pain intensity one hour after ingestion of the study medication. Secondary outcomes include: 1) the between treatment group difference in change in patients' rating of pain intensity two hours after ingestion of the study medication; 2) difference in proportion of patients who receive rescue medication; 3) difference in proportion of patients who would choose to take the study medication again if they returned to the ED with similar pain; 4) difference in proportion of patients who experience side effects.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ages 21 through 64 years of age
• Complaint of acute musculoskeletal pain in one or more extremity, defined as distal to and including the shoulder or hip joints.
• Pain of less than seven days duration
• Patient speaks Spanish or English
• The clinician plans to treat the patient in the ED with oral analgesics and is willing to treat the patient with opioid analgesics or up to 800 mg ibuprofen and 1000 mg acetaminophen
• Patient is going to receive imaging of the painful extremity
• Clinician judges patient to have capacity to provide informed consent

Exclusion Criteria:

• Patient does not have cell phone or cannot receive a verification phone call on their cell phone while in the ED
• Any use of methadone currently or previously
• Chronic condition requiring frequent pain management such as arthritis, sickle cell disease, fibromyalgia, or any neuropathy
• History of an adverse reaction to any of the study medications
• Opioids taken in the past 24 hours
• Ibuprofen or acetaminophen taken in past 24 hours
• Any other prescribed or over the counter topical or oral analgesics taken in past 24 hrs
• Pregnancy by either urine or serum human chorionic gonadotropin testing
• Breastfeeding per patient report
• History of peptic ulcer disease
• Medical condition that might affect metabolism of opioid analgesics, acetaminophen, or ibuprofen such as hepatitis, renal insufficiency, hypo- or hyperthyroidism, Addison's, or Cushing's disease
• Lacerations,
• Multiple injuries
• Taking any medicine that might interact with one of the study medications, such as antidepressant SSRI's or tricyclics, antipsychotics, anti-malaria medications quinidine or halofantrine, amiodarone or dronedarone, diphenhydramine, celecoxib, ranitidine, cimetidine, ritonavir, terbinafine, or St John's Wort

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oxycodone/acetaminophen (APAP); 5 mg oxycodone + 325 mg acetaminophen	Drug: oxycodone/APAP; Oxycodone/acetaminophen 5 mg-325 mg oral tablet; Other Names: Percocet
Active Comparator: hydrocodone/APAP; 5 mg hydrocodone + 300 mg acetaminophen	Drug: hydrocodone/APAP; Hydrocodone/Acetaminophen 5 Mg-300 Mg oral tablet; Other Names: Vicodin
Active Comparator: codeine/APAP; 30 mg codeine + 300 mg acetaminophen	Drug: codeine/APAP; Codeine/acetaminophen 30 mg-300mg oral tablet; Other Names: Tylenol # 3
Active Comparator: 400 ibuprofen/APAP; 400 mg ibuprofen + 1000 mg acetaminophen	Drug: 400 ibuprofen/APAP; ibuprofen/acetaminophen 400 mg-1000mg oral tablet; Other Names: Motrin, Tylenol
Active Comparator: 800 ibuprofen/APAP; 800 mg ibuprofen + 1000 mg acetaminophen	Drug: 800 ibuprofen/APAP; ibuprofen/acetaminophen 800 mg-1000 mg oral tablet; Other Names: Motrin, Tylenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline	Pain intensity measured by 11-point Numerical Rating Scale (NRS) of Pain 0 = no pain 10 = worse possible pain. Change calculated as NRS before medication administered (denoted as baseline) minus NRS 1-hour post-baseline. Higher scores mean more change which is the better outcome.	Prior to Ingestion of study medication to one hour after ingestion of the study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline	Pain intensity measured by 11-point Numerical Rating Scale (NRS) of Pain 0 = no pain 10=worst possible pain. Change is calculated as Numerical Rating Scale before medication is administered (denoted as baseline) minus NRS 2- hours past baseline. Higher numbers indicate better outcomes.	Prior to ingestion of study medication to 2 hours after ingestion of the study medication
Percentage of Patients Who Received Rescue Medication	Number of patients who received additional analgesics divided by total number of patients x 100	Entire two-hour time period
Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain	Number of patients who would choose to take study medication again divided by number of patients x 100. Question asked at end of two-hour time period	End of two-hour time period
Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication	Number of patients who experience side effects within one hour ofr ingestion of study medication divided by total number of patients x 100	From time of ingestion of study medication to one hour later
Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication	Number of patients who experience side effects in two hours after ingestion of study medication divided by total number of patients x 100	From time of ingestion of study medication to two hours later

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Investigators: Study Director: Benjamin Friedman, MD, Albert Einstein College of Medicine

Publications and helpful links

General Publications

• Bijur PE, Friedman BW, Irizarry E, Chang AK, Gallagher EJ. A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department. Ann Emerg Med. 2021 Mar;77(3):345-356. doi: 10.1016/j.annemergmed.2020.10.004. Epub 2020 Dec 23.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): November 14, 2019
• Study Completion (Actual): November 14, 2019

Study Registration Dates

• First Submitted: May 30, 2017
• First Submitted That Met QC Criteria: May 30, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 2, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: adult; acute pain; analgesics; Emergency Service, Hospital; Ibuprofen; Acetaminophen; oxycodone; emergency medicine; musculoskeletal pain; codeine; hydrocodone
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Emergencies; Musculoskeletal Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Acetaminophen; Ibuprofen; Oxycodone; Codeine; Hydrocodone
• Other Study ID Numbers: 2016-7322

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No