Effectiveness of Oxycodone Hydrochloride (Strong Opioid) vs Combination Acetaminophen and Codeine (Mild Opioid) for Subacute Pain After Fractures Managed Surgically: A Randomized Clinical Trial

IMPORTANCE: Patients with a surgically managed fracture are commonly discharged from the hospital with a strong opioid prescription, but limited evidence exists to support this practice. OBJECTIVE: To test the hypothesis that strong opioids provide greater analgesia than mild opioids over the first week postdischarge from hospital after fracture surgical treatment. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, superiority, randomized clinical trial was conducted at a single-center, major trauma hospital in Sydney, Australia. Participants were inpatients who had sustained an acute nonpathological facture of a long bone or the pelvis, patella, calcaneus, or talus who were treated with surgical fixation and enrolled from July 27, 2016, to August 22, 2017. Data were analyzed from June through October 2018. INTERVENTIONS: Initiation at discharge of oxycodone hydrochloride 5 mg of 10 mg (ie, 1 or 2 tablets) or combination acetaminophen and codeine 500 mg and 8 mg or 1000 mg and 16 mg (ie, 1 or 2 tablets) 4 times daily for a maximum duration of 3 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean of daily pain scores collected during week 1 of treatment measured using the Numerical Pain Rating Scale (NRS). Participants were asked to rate their mean pain over the previous 24 hours daily using an NRS score from 0 to 10, with 0 representing no pain and 10 representing the worst pain imaginable. The key secondary outcomes were EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) responses, worst pain, medication adverse events, global perceived effect, and return to work. RESULTS: A total of 120 patients with 1 or more acute orthopedic fractures requiring surgical fixation were randomized, including 59 patients in the strong-opioid group (43 [72.9%] men; mean [SD] age, 36.0 [14.1] years; mean oral morphine equivalent for days 1-7 of 32.9 mg) and 61 patients in the mild opioid group (47 [77.1%] men; mean [SD] age, 38.2 [13.5] years; mean oral morphine equivalent for days 1-7 of 5.5 mg). From days 1 to 7 postdischarge, the mean daily NRS mean pain score was 4.04 (95% Cl, 3.67 to 4.41) in the strong opioid group and 4.54 (95% Cl, 4.17 to 4.90) in the mild opioid group. The between-group difference of the primary outcome was not statistically significant (−0.50 [95% Cl, −1.11 to 0.12]; P = .11) despite a 6-fold increased dose of opioids being delivered in the strong opioid group. CONCLUSIONS AND RELEVANCE: This study found that treatment with strong opioid medication subacutely was not superior to treatment with milder medication for treatment of pain among patients with surgically managed orthopedic fractures. These findings suggest that ongoing first-line strong opioid use after discharge from the hospital should not be supported. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry No.: ACTRN12616000941460