Comparing the Efficacy of Oral Opioids for Outpatient Acute Pain Management After ED Discharge Discharge

Comparing the Efficacy of Oral Opioids for Outpatient Acute Pain Management After ED Discharge

There will be 3 randomized, double-blinded clinical trials to help determine which of commonly prescribed oral opioid combination is most effective in managing acute extremity pain after discharge from the adult emergency department. The first trial compares hydrocodone 5mg / acetaminophen 500mg to codeine 30mg/acetaminophen 300mg. The second trial compares oxycodone 5mg/acetaminophen 325mg to codeine 30mg/acetaminophen 300mg. The third trial compares oxycodone 5mg/acetaminophen 325 mg to hydrocodone 5mg/acetaminophen 325 mg.

Study Overview

• Status: Completed
• Conditions: Analgesia After ED Discharge for Extremity Injuries
• Intervention / Treatment: Drug: Hydrocodone (first trial); Drug: Codeine (first trial); Drug: Oxycodone (for second trial); Drug: Codeine (for second trial); Drug: Oxycodone (third trial); Drug: Hydrocodone (third trial)

Detailed Description

Eligible patients are those between the ages of 21 and 64 who present to the Emergency Department (ED) with a complaint of acute extremity pain of less than seven days duration in one or more extremities and for whom the clinician plans to discharge on an oral opioid for pain management. Patients will be excluded if they have ever taken methadone; have a chronic condition requiring frequent pain management such as sickle cell disease, fibromyalgia, or any neuropathy; report a history of an adverse reaction to any of the study medications; if they have taken prescribed opioids in the past 24 hours or if they report having ever taken recreational narcotics; if they have a medical condition that might affect their metabolism of opioid analgesics or acetaminophen; or if they take any medicine that might interact with one of the study medications. Patients will be referred by the attending physician or clinician and consent as well as the initial and follow-up data collections will be obtained by our team of trained bilingual (Spanish and English) salaried research associates who staff the ED 24 hours a day and 7 days a week.

In the first study, patients will be randomized to one of two experimental groups: hydrocodone 5mg / acetaminophen 500mg or codeine 30mg / acetaminophen 300mg. Randomization will be performed in blocks of 10 and determined by a sequence generated at http://www.randomization.com. The pharmacist working in an area inaccessible to ED staff will ensure proper blinding of the study by masking the medication and inserting it into unmarked gel capsules and filling any void with small amounts of lactose. A three-day supply (18 doses) of the blinded medications will be dispensed by the ED staff to the patient in the order determined by randomization accompanied by instructions to use one tablet of the medication every 4 hours as needed for pain and to avoid use of any other analgesics.

Using a power of 80%, a significance criterion of 0.5, and an estimated delta of 1.3 NRS units, a sample size of 85 patients per group. In order to account for those that do not end up taking the medicine, it is estimated that 120 patients per group will have to be enrolled.

Data will be collected on a standardized data collection instrument, entered by a trained data clerk, and reviewed and audited for accuracy and completeness. The investigators will calculate descriptive statistics for all variables: frequencies, means and standard deviations, medians and IQR, and proportions. Chi-square tests will be used to test differences between dichotomous variables, t-tests will be used to test mean differences. Multivariate models will be used if there are background variables that are unevenly distributed between the two groups. Variables associated with group membership with probability of 0.20 or less will be included in OLS multivariate regression or logistic regression models in order to test the role of group membership while accounting for chance baseline disparities. Interaction terms will be tested and dropped from the models if they were not statically significant at the 0.05 level. SPSS version 17 (Chicago, IL.) will be used to conduct all data analyses.

The second trial will be identical to the first trial with the exception of one of the study drugs, which will be oxycodone 5mg / acetaminophen 325 mg which will be compared to codeine 30mg / acetaminophen 300mg.

The third trial will be identical to the first and second trials with the exception of study drugs. This study will use oxycodone 5 mg/acetaminophen 325mg and hydrocodone 5mg/acetaminophen 325mg.

• Study Type: Interventional
• Enrollment (Actual): 720
• Phase: Phase 3

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:

• patient has complaint of acute extremity pain (less than 7 days duration)
• clinician plans to discharge on oral pain medication

Exclusion Criteria:

• patients on methadone
• chronic pain condition such as sickle cell anemia or fibromyalgia
• history of adverse reaction to one of the study medications
• taken prescribed opioids in the past 24 hrs
• have a medical condition that might alter the metabolism of one of the study medications (i.e. hepatitis, renal insufficiency, thyroid disease, Adrenal disease)
• Take a medication that might interact with one of the study medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrocodone (first trial); Hydrocodone 5mg / Acetaminophen 500mg. Patients instructed to take 1 dose every 4 hrs as needed for pain.	Drug: Hydrocodone (first trial); Patients will take 1 dose of Hydrocodone 5mg / Acetaminophen 500mg every 4 hours as needed for pain; Other Names: Vicodin (Hydrocodone 5mg / Acetaminophen 500mg)
Active Comparator: Codeine (first trial); Codeine 30mg / Acetaminophen 300mg. Patients instructed to take 1 dose every 4 hrs as needed for pain.	Drug: Codeine (first trial); Patients will take 1 dose of Codeine 30 mg / Acetaminophen 300 mg every 4 hours as needed for pain; Other Names: Tylenol # 3 (Codeine 30 mg/Acetaminophen 300 mg)
Experimental: Oxycodone (for second trial); Oxycodone 5mg / Acetaminophen 325mg. Patients instructed to take 1 dose every 4 hrs as needed for pain.	Drug: Oxycodone (for second trial); Patients will take 1 dose of Oxycodone 5 mg / Acetaminophen 325 mg every 4 hours as needed for pain; Other Names: Percocet (Oxycodone 5mg/Acetaminophen 325 mg)
Active Comparator: Codeine (for second trial); Codeine 30mg / Acetaminophen 300mg. Patients instructed to take 1 dose every 4 hrs as needed for pain.	Drug: Codeine (for second trial); Patients will take 1 dose of Codeine 30 mg / Acetaminophen 300 mg every 4 hours as needed for pain; Other Names: Tylenol # 3 (Codeine 30 mg/Acetaminophen 300 mg)
Experimental: Oxycodone (third trial); Oxycodone 5mg / Acetaminophen 325 mg. Patients instructed to take 1 dose every 4 hours as needed for pain.	Drug: Oxycodone (third trial); Patients will take 1 dose of Oxycodone 5mg / Acetaminophen 325 mg every 4 hours as needed for pain; Other Names: Oxycodone 5mg / Acetaminophen 325 mg
Active Comparator: Hydrocodone (third trial); Hydrocodone 5mg / Acetaminophen 325 mg. Patients instructed to take 1 dose every 4 hours as needed for pain.	Drug: Hydrocodone (third trial); Patients will take 1 dose of Hydrocodone 5 mg / Acetaminophen 325 mg every 4 hours as needed for pain.; Other Names: Hydrocodone 5mg / Acetaminophen 325 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Pain Intensity Score Before and After Last Dose.	Pain intensity is measured on the numerical rating scale (NRS) from 0 ("no pain") to 10 ("worst pain imaginable"). The difference in pain score is calculated by subtracting the average score 2 hours after pain medication is taken from the average pain score immediately before the pain medication is taken.	2 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Satisfaction With the Pain Medicine	Overall satisfaction with the oral opioid pain medication at 24 hours after discharge using a Likert scale. Patients will be asked to describe their overall experience as being very satisfied, satisfied, unsatisfied or very unsatisfied with the study medication.	24 hrs

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Andrew Chang, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 24, 2011
• First Submitted That Met QC Criteria: July 25, 2011
• First Posted (Estimate): July 26, 2011

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 27, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Emergency Medicine; Pain Management; Extremity Injuries
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Acetaminophen; Oxycodone; Codeine; Hydrocodone
• Other Study ID Numbers: 11-02-066