Musculoskeletal Pain
Conditions
Brief summary
This is an emergency department based randomized study of oxycodone/ acetaminophen versus acetaminophen alone for patients with acute musculoskeletal pain refractory to ibuprofen
Interventions
DRUGAcetaminophen
Acetaminophen 650mg
DRUGOxycodone
Oxycodone 10mg
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Acute musculoskeletal pain: Any pain attributable to muscles, bones, joints, tendons, ligaments or supporting structures, as determined by the clinical team, of 10 days duration or less. Prior to the onset of acute pain, patients cannot have experienced pain in the same body region during the prior six months * Pain has to be described as moderate or severe, when the patient is asked if the pain is mild, moderate or severe in intensity
Exclusion criteria
* Use of an non-steroidal anti-inflammatory drug within the previous six hours * Use of acetaminophen within the previous six hours * Use of an opioid within the previous ten days * Chronic pain, defined as any pain on \>50% of days for at least 3 months prior to onset of acute pain * Gout
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Assessment | 2 hours following treatment | Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): Change in Pain Assessment from baseline was determined using the Numeric Rating Scale (NRS) for evaluating pain. The rating was verbalized, and the subject was asked to estimate current pain intensity on an 11-point scale, where 0 indicated no pain at all and 10 indicated the worst imaginable pain. Positive mean changes in NRS scores were associated with increased pain relief. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adequacy of Analgesia | 2 hours following treatment | Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): Adequacy of analgesia was determined by querying the participants by asking a single question: Did the medication provided control your pain? Answer choices: Yes (it did); No (It did not); and Unsure. The number of participants responses were summarized by category. |
| Sustained Pain Relief | Up to 48 hours following medication administration | Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): Sustained pain relief was determined using a four-item ordinal scale. The rating was verbal and the subject was asked to describe their level of pain within two hours of medication administration and maintaining this level, without rescue medication, for 48 hours. The patients used the following descriptors: severe, moderate, mild, or none. For reporting responses of 'mild' and 'none' were aggregated into a single category and 'moderate' and severe' were aggregated into a separate category. |
| Satisfaction With Medication | 2 hours following treatment | Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): The number of participants demonstrating satisfaction with medication was determined by asking participants if the same medication regimen would be desired during a subsequent episode of pain. Possible responses included Yes, No or Unsure |
| Medication-related Adverse Events | 2 hours following treatment | Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): The number of participants demonstrating medication-related adverse events was tabulated by treatment arm/group. |
Countries
United States
Participant flow
Recruitment details
Enrollment into Stage 1 (open label stage) commenced on December 2019 in two urban emergency departments in Bronx, NY. Enrollment was halted from March-June 2020 due to COVID-19, and then resumed and concluded October 2020.
Pre-assignment details
During enrollment into Stage 1 (ibuprofen open label stage), 924 patients were screened for participation and 393 were enrolled. Of the 393, a total of 159 reported insufficient relief of pain from ibuprofen and requested more medication to treat the pain. Five patients who met criteria to progress to the randomized stage withdrew of their own volition. As such, 154 patients progressed to Stage 2. 77 were randomized to oxycodone/acetaminophen and 77 were randomized to acetaminophen alone.
Participants by arm
| Arm | Count |
|---|---|
| Ibuprofen + Acetaminophen Acetaminophen alone (Stage 2, Double blinded)
Acetaminophen: Acetaminophen 650mg PO | 77 |
| Ibuprofen + Oxycodone/Acetaminophen Oxycodone + Acetaminophen (Stage 2, Double blinded)
Acetaminophen: Acetaminophen 650mg PO
Oxycodone: Oxycodone 10mg PO | 77 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Stage 1 - Open Label | Satisfactory relief after ibuprofen administration. Exited study | 0 | 0 | 234 |
| Stage 1 - Open Label | Withdrawal by Subject | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Ibuprofen + Acetaminophen | Ibuprofen + Oxycodone/Acetaminophen | Total |
|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 12 | 38 years STANDARD_DEVIATION 13 | 37.5 years STANDARD_DEVIATION 12.5 |
| Pain Assessment | 8.2 score on a scale STANDARD_DEVIATION 1.2 | 8.3 score on a scale STANDARD_DEVIATION 1.3 | 8.3 score on a scale STANDARD_DEVIATION 1.3 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 77 participants | 77 participants | 393 participants |
| Sex: Female, Male Female | 36 Participants | 40 Participants | 76 Participants |
| Sex: Female, Male Male | 41 Participants | 37 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 76 | 0 / 0 |
| other Total, other adverse events | 6 / 74 | 18 / 76 | 0 / 0 |
| serious Total, serious adverse events | 0 / 74 | 0 / 76 | 0 / 0 |
Outcome results
Primary
Change in Pain Assessment
Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): Change in Pain Assessment from baseline was determined using the Numeric Rating Scale (NRS) for evaluating pain. The rating was verbalized, and the subject was asked to estimate current pain intensity on an 11-point scale, where 0 indicated no pain at all and 10 indicated the worst imaginable pain. Positive mean changes in NRS scores were associated with increased pain relief.
Time frame: 2 hours following treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen and Then Acetaminophen (Stage 2) | Change in Pain Assessment | 2.9 score on a scale | Standard Deviation 2.4 |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Change in Pain Assessment | 4.0 score on a scale | Standard Deviation 2.6 |
95% CI: [0.3, 1.9]
Secondary
Adequacy of Analgesia
Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): Adequacy of analgesia was determined by querying the participants by asking a single question: Did the medication provided control your pain? Answer choices: Yes (it did); No (It did not); and Unsure. The number of participants responses were summarized by category.
Time frame: 2 hours following treatment
Population: Responses for 3 participants in the 'Acetaminophen' arm and 1 participant in the 'Oxycodone + Acetaminophen' arm were unavailable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibuprofen and Then Acetaminophen (Stage 2) | Adequacy of Analgesia | Yes | 51 Participants |
| Ibuprofen and Then Acetaminophen (Stage 2) | Adequacy of Analgesia | No | 23 Participants |
| Ibuprofen and Then Acetaminophen (Stage 2) | Adequacy of Analgesia | Unsure | 0 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Adequacy of Analgesia | Yes | 59 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Adequacy of Analgesia | No | 17 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Adequacy of Analgesia | Unsure | 0 Participants |
95% CI: [-5, 23]
Secondary
Medication-related Adverse Events
Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): The number of participants demonstrating medication-related adverse events was tabulated by treatment arm/group.
Time frame: 2 hours following treatment
Population: Responses for 3 participants in the 'Acetaminophen' arm and 1 participant in the 'Oxycodone + Acetaminophen' arm were unavailable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibuprofen and Then Acetaminophen (Stage 2) | Medication-related Adverse Events | 7 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Medication-related Adverse Events | 26 Participants |
Secondary
Satisfaction With Medication
Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): The number of participants demonstrating satisfaction with medication was determined by asking participants if the same medication regimen would be desired during a subsequent episode of pain. Possible responses included Yes, No or Unsure
Time frame: 2 hours following treatment
Population: Responses for 4 participants in the 'Acetaminophen' arm and 1 participant in the 'Oxycodone + Acetaminophen' arm were unavailable.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibuprofen and Then Acetaminophen (Stage 2) | Satisfaction With Medication | Yes | 41 Participants |
| Ibuprofen and Then Acetaminophen (Stage 2) | Satisfaction With Medication | No | 22 Participants |
| Ibuprofen and Then Acetaminophen (Stage 2) | Satisfaction With Medication | Unsure | 10 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Satisfaction With Medication | Yes | 47 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Satisfaction With Medication | No | 18 Participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Satisfaction With Medication | Unsure | 11 Participants |
95% CI: [-10, 21]
Secondary
Sustained Pain Relief
Stage 1 (Open label): No Outcome Measures assessed Stage 2 (Double blinded): Sustained pain relief was determined using a four-item ordinal scale. The rating was verbal and the subject was asked to describe their level of pain within two hours of medication administration and maintaining this level, without rescue medication, for 48 hours. The patients used the following descriptors: severe, moderate, mild, or none. For reporting responses of 'mild' and 'none' were aggregated into a single category and 'moderate' and severe' were aggregated into a separate category.
Time frame: Up to 48 hours following medication administration
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ibuprofen and Then Acetaminophen (Stage 2) | Sustained Pain Relief | Mild/None | 33 participants |
| Ibuprofen and Then Acetaminophen (Stage 2) | Sustained Pain Relief | Moderate/Severe | 44 participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Sustained Pain Relief | Mild/None | 43 participants |
| Ibuprofen and Then Oxycodone/Acetaminophen (Stage 2) | Sustained Pain Relief | Moderate/Severe | 34 participants |
95% CI: [-3, 29]