Musculoskeletal Pain
Conditions
Keywords
acute pain, musculoskeletal pain, emergency medicine, Emergency Service, Hospital, analgesics, Acetaminophen, Ibuprofen, oxycodone, hydrocodone, codeine, adult
Brief summary
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).
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.
Interventions
DRUGoxycodone/APAP
Oxycodone/acetaminophen 5 mg-325 mg oral tablet
DRUGhydrocodone/APAP
Hydrocodone/Acetaminophen 5 Mg-300 Mg oral tablet
DRUGcodeine/APAP
Codeine/acetaminophen 30 mg-300mg oral tablet
DRUG400 ibuprofen/APAP
ibuprofen/acetaminophen 400 mg-1000mg oral tablet
DRUG800 ibuprofen/APAP
ibuprofen/acetaminophen 800 mg-1000 mg oral tablet
Sponsors
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A pharmacist working in an area inaccessible to ED staff will ensure blinding of the study by masking the medication and inserting it into identical unmarked gel capsules, filling any void with small amounts of lactose. Randomization will be performed in blocks of 10 determined by a sequence generated at http://www.randomization.com. The pharmacist will make up numbered research packets based on the random allocation list, each with 5 tablets containing the masked investigational medication. Research packets will be removed sequentially by the nurse from the Pyxis automated medical dispensing system and administered to the study patients in the ED.
Intervention model description
Randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline | Prior to Ingestion of study medication to one hour after ingestion of the study medication | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline | Prior to ingestion of study medication to 2 hours after ingestion of the study medication | 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. |
| Percentage of Patients Who Received Rescue Medication | Entire two-hour time period | Number of patients who received additional analgesics divided by total number of patients x 100 |
| Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain | End of two-hour time period | 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 |
| Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication | From time of ingestion of study medication to one hour later | Number of patients who experience side effects within one hour ofr ingestion of study medication divided by total number of patients x 100 |
| Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication | From time of ingestion of study medication to two hours later | Number of patients who experience side effects in two hours after ingestion of study medication divided by total number of patients x 100 |
Countries
United States
Participant flow
Recruitment details
Patients were recruited when they came into the ED with a complaint of pain. They were recruited in 2 academic EDs by trained, full-time, bilingual research associates from 11/26/2017 to 11/5/2019
Participants by arm
| Arm | Count |
|---|---|
| Oxycodone/APAP 5 mg oxycodone + 325 mg acetaminophen
oxycodone/APAP: Oxycodone/acetaminophen 5 mg-325 mg oral tablet | 120 |
| Hydrocodone/APAP 5 mg hydrocodone + 300 mg acetaminophen
hydrocodone/APAP: Hydrocodone/Acetaminophen 5 Mg-300 Mg oral tablet | 119 |
| Codeine/APAP 30 mg codeine + 300 mg acetaminophen
codeine/APAP: Codeine/acetaminophen 30 mg-300mg oral tablet | 120 |
| 400 Ibuprofen/APAP 400 mg ibuprofen + 1000 mg acetaminophen
400 ibuprofen/APAP: ibuprofen/acetaminophen 400 mg-1000mg oral tablet | 120 |
| 800 Ibuprofen/APAP 800 mg ibuprofen + 1000 mg acetaminophen
800 ibuprofen/APAP: ibuprofen/acetaminophen 800 mg-1000 mg oral tablet | 118 |
| Total | 597 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 2 Hour Follow-up | Withdrawal by Subject | 0 | 1 | 1 | 1 | 2 |
| Baseline | Medication dispensing system malfunction' | 0 | 1 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Oxycodone/APAP | Total | 800 Ibuprofen/APAP | 400 Ibuprofen/APAP | Codeine/APAP | Hydrocodone/APAP |
|---|---|---|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 12 | 37.4 years STANDARD_DEVIATION 12 | 38 years STANDARD_DEVIATION 13 | 36 years STANDARD_DEVIATION 12 | 38 years STANDARD_DEVIATION 12 | 39 years STANDARD_DEVIATION 12 |
| Diagnosis Contusion | 1 Participants | 34 Participants | 6 Participants | 6 Participants | 11 Participants | 10 Participants |
| Diagnosis Extremity Fracture | 21 Participants | 87 Participants | 14 Participants | 24 Participants | 17 Participants | 11 Participants |
| Diagnosis Muscle pain | 12 Participants | 66 Participants | 11 Participants | 13 Participants | 17 Participants | 13 Participants |
| Diagnosis Other | 11 Participants | 39 Participants | 5 Participants | 9 Participants | 7 Participants | 7 Participants |
| Diagnosis Sprain or Strain | 75 Participants | 371 Participants | 82 Participants | 68 Participants | 68 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 79 Participants | 313 Participants | 37 Participants | 32 Participants | 83 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 281 Participants | 81 Participants | 87 Participants | 37 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Initial pain intensity scale 0-6 | 5 Participants | 15 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants |
| Initial pain intensity scale 10 | 66 Participants | 338 Participants | 69 Participants | 70 Participants | 68 Participants | 65 Participants |
| Initial pain intensity scale 7 | 14 Participants | 50 Participants | 13 Participants | 6 Participants | 8 Participants | 9 Participants |
| Initial pain intensity scale 8 | 16 Participants | 99 Participants | 19 Participants | 19 Participants | 26 Participants | 19 Participants |
| Initial pain intensity scale 9 | 19 Participants | 95 Participants | 15 Participants | 22 Participants | 17 Participants | 22 Participants |
| Non-Pharmacologic interventions 0 | 63 Participants | 297 Participants | 51 Participants | 55 Participants | 64 Participants | 64 Participants |
| Non-Pharmacologic interventions greater than or equal to 1 | 57 Participants | 300 Participants | 67 Participants | 65 Participants | 56 Participants | 55 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 16 Participants | 1 Participants | 5 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 215 Participants | 47 Participants | 32 Participants | 46 Participants | 43 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 30 Participants | 147 Participants | 24 Participants | 31 Participants | 26 Participants | 36 Participants |
| Race (NIH/OMB) White | 40 Participants | 219 Participants | 46 Participants | 52 Participants | 44 Participants | 37 Participants |
| Region of Enrollment United States | 120 participants | 597 participants | 118 participants | 120 participants | 120 participants | 119 participants |
| Sex: Female, Male Female | 53 Participants | 265 Participants | 50 Participants | 53 Participants | 59 Participants | 50 Participants |
| Sex: Female, Male Male | 67 Participants | 332 Participants | 68 Participants | 67 Participants | 61 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 120 | 0 / 118 | 0 / 120 | 0 / 119 | 0 / 120 |
| other Total, other adverse events | 0 / 120 | 0 / 118 | 0 / 120 | 0 / 119 | 0 / 120 |
| serious Total, serious adverse events | 0 / 120 | 0 / 118 | 0 / 120 | 0 / 119 | 0 / 120 |
Outcome results
Primary
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.
Time frame: Prior to Ingestion of study medication to one hour after ingestion of the study medication
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 400 Ibuprofen/APAP | Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline | 3.0 Units on a scale |
| 800 Ibuprofen/APAP | Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline | 3.0 Units on a scale |
| Codeine/APAP | Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline | 3.4 Units on a scale |
| Hydrocodone/APAP | Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline | 3.1 Units on a scale |
| Oxycodone/APAP | Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline | 3.3 Units on a scale |
Comparison: The null hypothesis is that all means are equal. The alternate hypothesis is that one or more mean is less than or more than another.p-value: 0.69ANOVA
Secondary
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.
Time frame: Prior to ingestion of study medication to 2 hours after ingestion of the study medication
Population: Differences between population at 1 hour and 2 hour is due to patients leaving the Emergency Department before 2 hours post-baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 400 Ibuprofen/APAP | Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline | 4.3 units on a scale |
| 800 Ibuprofen/APAP | Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline | 4.6 units on a scale |
| Codeine/APAP | Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline | 4.4 units on a scale |
| Hydrocodone/APAP | Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline | 4.5 units on a scale |
| Oxycodone/APAP | Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline | 4.7 units on a scale |
p-value: 0.85ANOVA
Secondary
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
Time frame: From time of ingestion of study medication to two hours later
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 400 Ibuprofen/APAP | Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication | 31 Participants |
| 800 Ibuprofen/APAP | Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication | 44 Participants |
| Codeine/APAP | Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication | 40 Participants |
| Hydrocodone/APAP | Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication | 51 Participants |
| Oxycodone/APAP | Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication | 49 Participants |
p-value: 0.0501Chi-squared
Secondary
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
Time frame: From time of ingestion of study medication to one hour later
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 400 Ibuprofen/APAP | Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication | 26 Participants |
| 800 Ibuprofen/APAP | Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication | 37 Participants |
| Codeine/APAP | Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication | 33 Participants |
| Hydrocodone/APAP | Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication | 34 Participants |
| Oxycodone/APAP | Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication | 37 Participants |
p-value: 0.46Chi-squared
Secondary
Percentage of Patients Who Received Rescue Medication
Number of patients who received additional analgesics divided by total number of patients x 100
Time frame: Entire two-hour time period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 400 Ibuprofen/APAP | Percentage of Patients Who Received Rescue Medication | 29 Participants |
| 800 Ibuprofen/APAP | Percentage of Patients Who Received Rescue Medication | 28 Participants |
| Codeine/APAP | Percentage of Patients Who Received Rescue Medication | 26 Participants |
| Hydrocodone/APAP | Percentage of Patients Who Received Rescue Medication | 27 Participants |
| Oxycodone/APAP | Percentage of Patients Who Received Rescue Medication | 28 Participants |
p-value: 0.99Chi-squared
Secondary
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
Time frame: End of two-hour time period
Population: Missing data: 1 from codeine/APAP arm, 1 from hydrocodone/APAP arm, 2 from oxycodone/APAP arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 400 Ibuprofen/APAP | Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain | 78 Participants |
| 800 Ibuprofen/APAP | Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain | 83 Participants |
| Codeine/APAP | Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain | 75 Participants |
| Hydrocodone/APAP | Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain | 89 Participants |
| Oxycodone/APAP | Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain | 81 Participants |