A randomized controlled trial of oxycodone/acetaminophen versus acetaminophen alone for emergency department patients with musculoskeletal pain refractory to ibuprofen

Background: Use of oral opioids does not result in more pain relief than nonopioid alternatives when administered to patients as first-line treatment for acute musculoskeletal pain. This study compared the efficacy of oxycodone/acetaminophen to that of acetaminophen alone as second-line treatment for patients with acute musculoskeletal pain who were administered prescription-strength ibuprofen and reported insufficient relief 1 h later. Methods: A randomized, double-blind study was conducted in two urban emergency departments. Opioid-naïve patients ≥ 18 years with an acute musculoskeletal injury were administered ibuprofen 600 mg as part of the study protocol. Those who reported insufficient relief 1 h later were randomized (1:1 ratio) to oxycodone 10 mg/acetaminophen 650 mg or acetaminophen 650 mg. The primary outcome was improvement in 0 to 10 pain scale between randomization and 2 h later. We also assessed medication-associated adverse events. A sample size calculation, built around a minimum clinically important difference of 1.3 units, determined the need for 154 patients. Results: We screened 924 patients and enrolled 393. All 393 received ibuprofen. A total of 159 (40%) patients reported inadequate relief after 1 h had elapsed. A total of 154 of these were randomized, 77 to oxycodone/acetaminophen and 77 to acetaminophen. Baseline characteristics were comparable. Among patients randomized to oxycodone/acetaminophen, mean (±SD) improvement in 0 to 10 pain scale was 4.0 (±2.6) versus 2.9 (±2.4) in the acetaminophen arm. The 95% confidence interval (CI) for the mean difference of 1.1 was 0.3 to 1.9. Among patients who received oxycodone/acetaminophen, 26 of 76 (34%) reported any medication-related adverse event versus seven of 74 (9%) participants who received acetaminophen. The 95% CI for the between-group difference of 25% was 12% to 37%). Conclusion: Among patients with acute musculoskeletal pain refractory to oral ibuprofen, oxycodone/acetaminophen resulted in slightly greater pain relief than acetaminophen, but this was associated with more medication-related adverse events.