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

Abstract

Background: Opioids and acetaminophen are both widely used to relieve pain after nonoperative treatment of limb fractures, but evidence for superiority of opioids versus acetaminophen is lacking. In this study we aim to determine whether acetaminophen is noninferior to the acetaminophen/oxycodone combination for pain relief after nonoperative fixation of an extremity limb fracture. We hypothesize that acetaminophen is noninferior to the acetaminophen/oxycodone combination. Methods: A double-blind, randomized controlled trial will be conducted. Power analysis determined that 1,226 participants will be needed (p<0.05, power 90%). Patients with acute limb fracture who receive nonoperative treatment will be recruited and randomly allocated into two groups: the intervention group will receive oral oxycodone (5 mg)/acetaminophen (325 mg), and the control group will receive acetaminophen (650 mg) only. 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 dimensions’ questionnaire (EQ-5d), self-rated satisfaction with the analgesia produced, self-reported nighttime sleep duration, number of intervention or control pills used, 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 t-student 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 noninferior to the combination of acetaminophen and oxycodone in relieving objectively measured pain after nonoperative treatment of limb fractures in adults. It is hopeful to provide a safe and effective analgesic plan for such patients. Trial Registration: ChiCTR registry: ChiCTR1800017015 ( http://www.chictr.org.cn/showproj.aspx?proj=28612). Registered on 8 July 2018. Keywords: Opioids, acetaminophen, fracture, nonoperative treatment.