NCT06201676

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

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 458 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The goal of this randomized clinical trial is to learn if the use of a low-dose nonsteroidal anti-inflammatory drug (NSAID), ketorolac, reduces the rate of chronic opioid use in orthopaedic trauma patients. The main questions this study aims to answer are: 1. Are patients who are given scheduled ketorolac during the first five days of the perioperative period in combination with standard of care (SOC) multimodal analgesia (MMA) less likely to develop chronic opioid use at 6 months after injury compared to patients who SOC MMA alone? 2. Does scheduled ketorolac during the first five days of the perioperative period improve functional responses to pain at discharge, 3 months, and 6 months after injury? 3. Does early pain control provided by ketorolac decrease chronic opioid use through decreased acute pain and opioid use, improved functional responses to pain, or both? Participants will be enrolled and randomized to either the ketorolac (treatment) group or the SOC group. Patients randomized to the ketorolac group will receive ketorolac every 6 hours for up to five days during the perioperative period; patients discharged prior to completing the five-day regimen will complete the remainder of treatment with oral ketorolac. Pain and opioid use will be measured daily during the five-day treatment period. Opioid use will be measured and functional response to pain surveys will be obtained at discharge, 2 weeks, 6 weeks, 3 months, and 6 months after injury. Researchers will compare patients receiving ketorolac (treatment) plus SOC versus those receiving SOC alone to determine if ketorolac reduces chronic opioid use and improves the functional response to pain.

Detailed description

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.

Conditions

• Orthopaedic Trauma
• Chronic Opioid Use

Interventions

Type	Name	Description
DRUG	Ketorolac Injection	Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits analgesic activity in animal models. The mechanism of action of ketorolac, like that of other NSAIDs, is not completely understood but may be related to prostaglandin Reference ID: 3281582 3 synthetase inhibition. The biological activity of ketorolac tromethamine is associated with the S-form. Ketorolac tromethamine possesses no sedative or anxiolytic properties.
OTHER	Standard of Care (SOC) Multimodal Analgesia	Standard of care (SOC) multimodal analgesia as determined by each participating site's institutional protocol for perioperative pain management in orthopaedic trauma patients. SOC may include opioids, acetaminophen, regional anesthesia, and other non-NSAID analgesic modalities. Scheduled nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, are not permitted during the five-day perioperative treatment period.

Timeline

• Start date: 2025-02-28
• Primary completion: 2026-12-31
• Completion: 2027-08-31
• First posted: 2024-01-11
• Last updated: 2026-02-24

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study