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

NCT06201676 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: 2023P003287HT9425-23-1-0413
• Study Type: interventional
• Target: 458
• Locations: 1 country
• Sites: 2

Brief 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. 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. 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. 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?

Conditions

Chronic Opioid Use; Orthopaedic Trauma

Keywords

orthopaedic trauma; chronic opioid use; NSAID; IV ketorolac; acute pain management

Outcome Measures

Primary Outcomes (1)

• Chronic Opioid Use

  Defined as continued opioid use at 6 months post-trauma

  6 months

Secondary Outcomes (6)

• Brief Pain Inventory (BPI)

  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)

  Hospital Discharge (up to 2 weeks), 2 weeks, 6 weeks, 3 months, and 6 months post-trauma

• Brief Resilience Scale (BRS)

  Hospital Discharge (up to 2 weeks), 2 weeks, 6 weeks, 3 months, and 6 months post-trauma

• Visual Analogue Scale (VAS)

  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)

  Enrollment, First Five Hospital Days, Hospital Discharge (up to 2 weeks)

Study Arms (2)

Standard of Care (SOC) + Ketorolac

EXPERIMENTAL

The treatment arm will receive a scheduled five-day course of low-dose ketorolac in addition to standard of care (SOC) multimodal analgesia according to each site's institutional protocol. Ketorolac will be administered intravenously at a dose of 15 mg every 6 hours during the perioperative period. Participants discharged prior to completing the five-day regimen will complete the remaining treatment with oral ketorolac 10 mg every 8 hours.

Drug: Ketorolac Injection; Other: Standard of Care (SOC) Multimodal Analgesia

Standard of Care (SOC)

ACTIVE COMPARATOR

The control arm will receive standard of care (SOC) multimodal analgesia according to each site's institutional protocol.

Other: Standard of Care (SOC) Multimodal Analgesia

Interventions

Ketorolac Injection DRUG

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.

Also known as: Toradol

Standard of Care (SOC) + Ketorolac

Standard of Care (SOC) Multimodal Analgesia OTHER

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.

Standard of Care (SOC); Standard of Care (SOC) + Ketorolac

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age: 18-70
• Patient or legally authorized representative (LAR) able to provide consent
• Patients with acute musculoskeletal trauma requiring surgical fixation (i.e. ORIF with plates and screws and/or intramedullary nailing)
• Anticipated hospital admission
• Patients who speak English or Spanish
• Patients who can be followed at the enrolling facility for at least 6 months

You may not qualify if:

• Patient age \< 18 or \> 70 years
• Patients with injury more than 24 hours prior to evaluation
• Patients with active hemorrhagic shock or risk of significant hemorrhage
• Patients who are pregnant or breastfeeding
• Patients with a history of active gastrointestinal bleeds or ulceration
• Patients with chronic use of steroids or immune-modulating drugs or history of organ transplantation
• Patients with preexisting chronic renal, liver, heart, or lung disease
• Patients with a creatinine ≥ 1.30 mg/dL during enrollment
• Patients with history of myocardial infarction, stroke, or bleeding disorder
• Patients with head or chest injury requiring surgical intervention
• Patients with allergy to ketorolac or hypersensitivity to aspirin
• Patients receiving chronic opioid therapy or treatment for opioid use disorder
• Patients who are current IV drug users
• Patients who require a daily NSAID or aspirin regimen, except for daily low-dose aspirin (81 mg)
• Patients with insufficient follow-up or anticipated difficulty in completing follow-up at a study site for a minimum of 6 months due to any of the follow reasons: death, no follow-up after initial discharge, severe psychiatric conditions, unstable living conditions, planned follow-up at another medical center not participating in this study, live far away from the clinic, and/or incarcerated

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• United States Department of Defense: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Related Links

• Pilot Study Results
• Pilot Study Results #2

MeSH Terms

Interventions

Ketorolac; Ketorolac Tromethamine; Standard of Care

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Arun Aneja, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arun Aneja, MD, PhD

CONTACT

617-726-6546; aaneja@mgh.harvard.edu

Adam N Musick, MD

CONTACT

423-765-3223; adamnmusick@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Following participant enrollment and randomization, participants, treating clinicians, study investigators, and research personnel are aware of treatment group assignment. Randomization is performed using a computer-generated randomization schedule prepared in consultation with the study statistician and implemented by the Clinical Trials Pharmacy at each participating site. Treatment assignments are disclosed to the clinical and research teams after randomization to allow appropriate administration of ketorolac. The study statistician will conduct analyses according to randomized group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Parallel, two-arm, randomized controlled trial

Study Record Dates

• First Submitted: December 16, 2023
• First Posted: January 11, 2024
• Study Start: February 28, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)