Low-Dose Short-Term Ketorolac to Reduce Chronic Opioid Use in Orthopaedic Polytrauma Patients

Background: Post-traumatic pain (PTP) can be difficult to control in orthopaedic trauma patients, particularly those with multiple injuries. Currently, opioids serve as the cornerstone for pain management despite their potential for complications including chronic use. Given this, it is not surprising that new-onset opioid abuse is a leading cause of complications following orthopaedic trauma and can be a limiting factor in delaying and/or safely resuming pre-injury responsibilities. Changes in pain management are needed to help military personnel and civilians expeditiously and safely return to their pre-injury duty. Early short-term scheduled ketorolac treatment has been shown to decrease acute pain and short and mid-term opioid use but whether this translates into decreased chronic opioid use is unknown.

Hypothesis/Objective: This study attempts to determine whether an early scheduled short-term course of ketorolac treatment has a sustained impact by decreasing chronic opioid use. The study will also investigate whether this treatment improves function and resilience as well as whether early pain control and/or the functional response to pain mediate (i.e. are responsible for / explain) the effect of the ketorolac intervention on chronic opioid use.

Specific Aims:

Aim 1: Determine whether orthopaedic trauma patients who receive a scheduled five-day course of low-dose ketorolac (15 mg IV every six hours, with transition to 10 mg orally every eight hours if discharged prior to completion of the five-day regimen) in combination with standard of care (SOC) multimodal analgesia (MMA) are less likely to develop chronic opioid use, defined as continued use at six months post-injury, compared to patients receiving SOC MMA alone.

Aim 2: Determine if patients who received a consistent five-day course of low-dose ketorolac have an improved functional response to pain measured via: 1) Brief Pain Inventory (BPI), 2) Patient-Reported Outcomes Measurement Information System - Pain Interference (PROMIS-PI), and 3) Brief Resilience Scale (BRS) scores at discharge, 3 months, and 6 months post-injury. Secondary pain outcome measures such as pain VAS and MME data will also be compared between the two groups.

Aim 3: Determine (1) the extent to which early pain control during the intervention, assessed using pain VAS and MME intake, mediates the effect of ketorolac on chronic opioid use, (2) the extent to which early pain control mediates the effect of ketorolac on the functional response to pain measures, assessed using BPI, PROMIS-PI, and BRS, and (3) the extent to which early pain control and the functional response to pain in combination or isolation mediate the effect of ketorolac on chronic opioid use.

Study Design: Adult patients (aged 18 to 70 years) with an acute orthopaedic traumatic injury undergoing operative fixation and admitted at participating Level 1 trauma centers will be enrolled. Once enrolled, patient randomization will be stratified by site and NISS score categorization (either 1-15 or greater than 15). Experienced clinical research staff will prospectively identify patients with strict adherence to all inclusion and exclusion criteria. Participants will be randomized to treatment (15 mg of ketorolac IV every 6 hours for up to 5 days in combination with SOC MMA; patients discharged prior to completing the five-day regimen will complete the remaining treatment with oral ketorolac 10 mg every 8 hours) or to SOC MMA alone. Measures of the functional response to pain including the BPI, PROMIS-PI, and BRS will be collected at hospital discharge and 3- and 6-months post-injury. Outcome measures of pain including VAS and MME will be recorded at enrollment, during the first five days of inpatient admission, at discharge, and at clinic follow-ups. The treatment and SOC groups will be compared using the intention-to-treat analyses across the primary and secondary outcomes. Mediation analyses will be used to understand how early pain control and the functional response to pain mediate the effect or lack of effect on chronic opioid use to better understand the factors that lead to this devastating complication.

• Brief Pain Inventory (BPI) [Срок оценки: Enrollment, Hospital Discharge (up to 2 weeks), 2 weeks, 6 weeks, 3 months, and 6 months post-trauma]
• Patient-Reported Outcomes Measurement Information System-Pain Interference (PROMIS-PI) [Срок оценки: Hospital Discharge (up to 2 weeks), 2 weeks, 6 weeks, 3 months, and 6 months post-trauma]
• Brief Resilience Scale (BRS) [Срок оценки: Hospital Discharge (up to 2 weeks), 2 weeks, 6 weeks, 3 months, and 6 months post-trauma]
• Visual Analogue Scale (VAS) [Срок оценки: Enrollment, First Five Hospital Days, Hospital Discharge (up to 2 weeks), 2 weeks, 6 weeks, 3 months, and 6 months post-trauma]
• Morphine Milligram Equivalents (MME) [Срок оценки: Enrollment, First Five Hospital Days, Hospital Discharge (up to 2 weeks)]
• Opioid Use [Срок оценки: 2 weeks, 6 weeks, 3 months, and 6 months post-trauma]