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

NCT ID: NCT06027099

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 375 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-05
• Study Completion Date: 2028-07-31

Brief Summary

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.

Detailed 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.

Conditions

Chronic Pain; Back Pain; Neck Pain; Opioid Misuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MI-Opioid Taper and tizanidine

Group Type: EXPERIMENTAL

Tizanidine

Intervention Type: DRUG

Tizanidine 2mg three times a day for 5 weeks after surgery

MI-Opioid Taper

Intervention Type: BEHAVIORAL

Motivational Interviewing (MI) and guided Opioid Tapering support adapting MI principles for enhancing motivation to change in pain treatment and tailoring key MI tools to postoperative opioid use delivered through weekly phone calls from weeks 2 to 7, and at week 11. The guided opioid tapering protocol will be a 25% total daily opioid dose reduction every 7 days with opioid discontinuation 7 days after reaching 1 opioid pill per day.

MI-Opioid Taper and placebo

Group Type: EXPERIMENTAL

MI-Opioid Taper

Intervention Type: BEHAVIORAL

Motivational Interviewing (MI) and guided Opioid Tapering support adapting MI principles for enhancing motivation to change in pain treatment and tailoring key MI tools to postoperative opioid use delivered through weekly phone calls from weeks 2 to 7, and at week 11. The guided opioid tapering protocol will be a 25% total daily opioid dose reduction every 7 days with opioid discontinuation 7 days after reaching 1 opioid pill per day.

Placebo

Intervention Type: DRUG

1 tablet three times a day for 5 weeks after surgery

Enhanced Usual Care

Group Type: ACTIVE_COMPARATOR

Enhanced Usual Care

Intervention Type: BEHAVIORAL

Participants will receive weekly phone calls from weeks 2 to 7, and at week 11. 1 topic per call will be reviewed in this sequence:1) standardized instructions on taking opioid medications after surgery, 2) safe opioid use, 3) avoiding medication errors, 4) local mental health resources and 988 Suicide \& Crisis lifeline, 5) disposal of unused medications, 6) prescription drug abuse, and 7) complementary health approaches for chronic pain. Education materials will be reviewed in a didactic style without a tailored discussion.

Interventions

Tizanidine

Tizanidine 2mg three times a day for 5 weeks after surgery

Intervention Type: DRUG

MI-Opioid Taper

Motivational Interviewing (MI) and guided Opioid Tapering support adapting MI principles for enhancing motivation to change in pain treatment and tailoring key MI tools to postoperative opioid use delivered through weekly phone calls from weeks 2 to 7, and at week 11. The guided opioid tapering protocol will be a 25% total daily opioid dose reduction every 7 days with opioid discontinuation 7 days after reaching 1 opioid pill per day.

Intervention Type: BEHAVIORAL

Placebo

1 tablet three times a day for 5 weeks after surgery

Intervention Type: DRUG

Enhanced Usual Care

Participants will receive weekly phone calls from weeks 2 to 7, and at week 11. 1 topic per call will be reviewed in this sequence:1) standardized instructions on taking opioid medications after surgery, 2) safe opioid use, 3) avoiding medication errors, 4) local mental health resources and 988 Suicide \& Crisis lifeline, 5) disposal of unused medications, 6) prescription drug abuse, and 7) complementary health approaches for chronic pain. Education materials will be reviewed in a didactic style without a tailored discussion.

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Hah

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Stanford University Hospital

Stanford, California, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Jennifer Hah, MD, MS

Role: primary

jhah@stanford.edu

650-724-3193

Other Identifiers

71909

Identifier Type: -

Identifier Source: org_study_id