An RCT of oxycodone/ acetaminophen versus acetaminophen alone for emergency department patients with musculoskeletal pain refractory to ibuprofen.

Friedman, Benjamin W; Irizarry, Eddie; Feliciano, Carmen; Izzo, Albert J; Borrayes, Lester; Restivo, Andrew; Costa, Vincent; Bijur, Polly E

BACKGROUND Use of oral opioids does not result in more pain relief than non-opioid 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 1hour later. METHODS A randomized, double-blind study conducted in two urban EDs. Opioid-naïve patients ≥18 years with an acute musculoskeletal injury were administered ibuprofen 600mg as part of the study protocol. Those who reported insufficient relief one hour later were randomized (1:1ratio) to oxycodone10mg/ acetaminophen 650mg or acetaminophen 650mg. The primary outcome was improvement in 0-10 pain scale between randomization and 2 hours 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. 159(40%) patients reported inadequate relief after 1hour had elapsed. 154 of these were randomized, 77 to oxycodone/acetaminophen and 77 to acetaminophen. Baseline characteristics were comparable. Among patients randomized to oxycodone/acetaminophen, mean improvement in 0-10 pain scale was 4.0(SD: 2.6) versus 2.9(SD:2.4) in the acetaminophen arm. The 95%CI for the mean difference of 1.1 was 0.3, 1.9. Among patients who received oxycodone/acetaminophen, 26/76 (34%) reported any medication related adverse event versus 7/74 (9%) participants who received acetaminophen. The 95%CI for the between group difference of 25% was (12, 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.