Low-Dose Short-Term Ketorolac to Reduce Chronic Opioid Use in Orthopaedic Polytrauma Patients
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 458
- 试验地点
- 2
- 主要终点
- Chronic Opioid Use
研究概览
简要总结
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:
- 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?
- 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?
- 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Standard of Care (SOC) + Ketorolac
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.
干预措施: Ketorolac Injection (Drug)
Standard of Care (SOC) + Ketorolac
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.
干预措施: Standard of Care (SOC) Multimodal Analgesia (Other)
Standard of Care (SOC)
The control arm will receive standard of care (SOC) multimodal analgesia according to each site's institutional protocol.
干预措施: Standard of Care (SOC) Multimodal Analgesia (Other)
结局指标
主要结局
Chronic Opioid Use
时间窗: 6 months
Defined as continued opioid use at 6 months post-trauma
次要结局
- 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)
- Brief Pain Inventory (BPI)(Enrollment, 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))
- Opioid Use(2 weeks, 6 weeks, 3 months, and 6 months post-trauma)
研究者
Arun Aneja, MD, PhD
Associate Professor
Massachusetts General Hospital