Efficacy of acetaminophen with and without oxycodone for analgesia in non-operative treatment of extremity fractures in adults: protocol for a double-blind randomized clinical trial

Background Opioids and acetaminophen are both widely used to relieve pain after non-operative treatment of limb fractures, but evidence for the superiority of opioids versus acetaminophen is lacking. In this study, we aim to determine whether acetaminophen is non-inferior to the acetaminophen/oxycodone combination for pain relief after non-operative fixation of an extremity limb fracture. We hypothesize that acetaminophen is non-inferior to the acetaminophen/oxycodone combination. Methods A double-blind randomized controlled trial will be conducted. Power analysis determined that 1226 participants will be needed (P <0.05, power 90%). Patients with acute limb fracture who receive non-operative treatment will be recruited and randomly allocated into two groups: the intervention group will receive oral oxycodone (10 mg) and acetaminophen (650 mg), and the control group will receive acetaminophen (650 mg) only. All participants will be instructed to take one pill of study medication on an as-needed basis and no more frequently than once every 8 h. The primary outcome measure will be scores on the 11-point Numeric Rating Scale (NRS-11) over 14 days. Secondary outcome measures are scores on the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), EuroQol five-dimension questionnaire (EQ-5D), self-rated satisfaction with the analgesia produced, self-reported nighttime sleep duration, number of intervention or control pills used, and total duration for taking intervention or control medication. Change of pain scores and the number of times that analgesic drugs were taken in the two groups will be statistically evaluated with Student t tests according to their fracture site. Discussion This study will be a randomized controlled trial that is adequately powered to test the hypothesis that acetaminophen is non-inferior to the combination of acetaminophen and oxycodone in relieving objectively measured pain after non-operative treatment of limb fractures in adults. It will hopefully provide a safe and effective analgesic plan for such patients.