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CARES-Spine (Comprehensive Analgesic, Recovery, and Education Support for Spine Surgery) Trial

CARES-Spine (Comprehensive Analgesic, Recovery, and Education Support for Spine Surgery) Trial

Recruiting
18-64 years
All
Phase 3

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Overview

Three-arm randomized controlled trial, of Motivational Interviewing and guided Opioid Tapering support (MI-Opioid Taper) and tizanidine vs. MI-Opioid Taper and placebo vs. enhanced usual care to promote postoperative opioid cessation and pain cessation and reduce the incidence of postoperative opioid misuse among patients undergoing spine surgery.

Description

In this Type 1 hybrid effectiveness-implementation three-arm parallel RCT, 375 patients with preoperative LTOU undergoing spine surgery will be recruited across 4 sites (Stanford, Harvard, Wake Forest, U. of Kansas) and randomized to 1 of 3 groups (MI-Opioid Taper and tizanidine, MI-Opioid Taper and placebo, enhanced usual care) and followed for 12 months. The primary outcome is time to baseline opioid use. Secondary outcomes are time to opioid cessation, opioid dispensing cessation, pain cessation, and risk of postoperative opioid misuse. We will examine motivation for change, change talk, and reduction in pain as mediators of treatment effects and characterize treatment interactions with participant attributes in predicting both treatment engagement and efficacy. A mixed-methods evaluation using the RE-AIM framework will explore barriers and facilitators to future larger-scale implementation of MI-Opioid Taper. The project will address the unmet needs of patients on long-term opioid use presenting for surgery in need of precision postoperative pain care to minimize opioid-related harms.

Eligibility

Inclusion Criteria:

  • Adults aged 18-64 scheduled for elective spine surgery for lumbar or cervical degenerative disease (e.g. lumbar or cervical disc herniation, lumbar or cervical spinal stenosis, lumbar or cervical degenerative spondylolisthesis, lumbar or cervical disc degeneration, or degenerative cervical myelopathy including cervical spondylotic myelopathy).
    • Preoperative long-term opioid use (Defined as ≥ 90-day duration of use in the 4 months preceding surgery either via self-report or state PDMP.
    • Participants must report at least one of the following on preoperative
      assessments

Current Opioid Misuse Measure (COMM) score greater than or equal to 9 Answering "Yes" to any of the following items on the modified Brief Pain Inventory (BPI)1) Over the past 24 hours have you needed to take your pain medication to help you sleep; 2)Have you taken any pain medications for any reason other than your pain, such as to reduce anxiety or improve mood? 3) Have you taken more pain medication than was prescribed to you in the past 24 hours? Score of greater than or equal to 2 on any Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS-1) item Positive Alcohol Use Disorders Identification Test (AUDIT-C) score (greater than or equal to 4 for men, greater than or equal to 3 for women)

  • Elevated opioid use 14 days after surgery compared to baseline daily OME Defined as average daily OME assessed over 3 days 1 week before surgery compared to average daily OME reported on postoperative days 12 to 14 to account for as-needed dosing and day-to-day variations in opioid use.
  • English-speaking
  • Ability and willingness to complete online assessments

Exclusion Criteria:

  • Infection, tumor, or fracture at the operative site
  • Allergy or intolerance to tizanidine
  • Current use of tizanidine
  • Renal impairment
  • Hepatic impairment including cirrhosis or elevated enzymes
  • Concurrent use of other α2-adrenergic agonists, skeletal muscle relaxants
  • Concurrent use of: fluvoxamine, ciprofloxacin,zileuton, fluoroquinolones, antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine, famotidine, oral contraceptive pills, acyclovir, ticlopidine, and fexinidazole
  • Pre-existing hypotension, sedation, dizziness, severe respiratory insufficiency.
  • Opioid Use Disorder
  • Suicidality as assessed by the Patient Health Questionnaire-9 (PHQ-9) Question 9 score ≥ 1
  • Pregnancy, breastfeeding, or planning to conceive
  • Cancer diagnosis, active malignant neoplasm (metastatic or local) or evidence of paraneoplastic syndrome
  • Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status)
  • Participating in another clinical trial with an active treatment arm

Study details
    Chronic Pain
    Back Pain
    Neck Pain
    Opioid Misuse

NCT06027099

Stanford University

15 October 2025

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