CARES: Comprehensive Analgesic, Recovery, and Education Support for Surgery

Integrating Tailored Postoperative Opioid Tapering and Pain Management Support for Patients on Long-Term Opioid Use Presenting for Surgery

This trial tests whether combining motivational interviewing–guided opioid tapering with the medication tizanidine helps adults who used opioids long-term before elective surgery stop or return to their pre-surgery opioid levels sooner and recover from pain faster than enhanced usual care.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 375 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Stanford University (Academic / other)
• Locations: 4 sites (Stanford, California and 3 other locations)
• Trial ID: NCT06027099 on ClinicalTrials.gov

What this trial studies

This phase 3, three-arm, parallel randomized controlled trial will enroll 375 adults with preoperative long-term opioid use across four academic centers and randomize them equally to MI-guided opioid taper plus tizanidine, MI-guided taper plus placebo, or enhanced usual care. Participants will be followed for 12 months after elective surgery with structured assessments of opioid use, pain resolution, and opioid misuse. The primary outcome is time to return to baseline opioid use, with secondary outcomes including time to opioid cessation, time to pain cessation, and incidence of postoperative opioid misuse. The trial uses a Type 1 hybrid effectiveness-implementation design to also examine behavioral mediators and implementation factors.

Who should consider this trial

Good fit: Adults aged 18–75 who speak English, are scheduled for elective surgery at one of the participating centers, and had preoperative long-term opioid use (≥60 days of opioid supply in the prior 180 days) are the intended participants.

Not a fit: People not meeting the long-term opioid use definition, those having emergency surgery, non-English speakers, or patients outside the participating centers are unlikely to benefit from or be eligible for this protocol.

Why it matters

Potential benefit: If successful, the combined counseling and medication approach could shorten the time patients need opioids after surgery, speed pain recovery, and lower the risk of postoperative opioid misuse.

How similar studies have performed: Motivational interviewing and structured opioid tapering have shown promise in prior studies for reducing opioid use, but combining MI-guided tapering with tizanidine for postoperative opioid reduction is relatively novel and not yet proven in large phase 3 trials.

Eligibility criteria

INCLUSION CRITERIA:

* 18 to 75 years of age
* Able to speak, write, and read fluently in English
* Scheduled for elective surgery at

  * Stanford University Medical Center,
  * Brigham and Women's Hospital (Harvard University),
  * Atrium Health Wake Forest Baptist Medical Center (Wake Forest University), or
  * University of Kansas Medical Center
* Preoperative long-term opioid use (Defined as ≥ 60-day supply of opioids in the 180-day period prior to surgery), identified via self-report, state Prescription Drug Monitoring Program (PDMP), or Electronic Medical Records (EHR). Days may be nonconsecutive, and actual use of opioid supply is not required.
* Willing and able to complete online assessments and study calls independently
* On the preoperative Baseline assessments, least one of the following:

  * Current Opioid Misuse Measure (COMM-17): score ≥ 9
  * Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS-1): Reported use more frequent than "Never" on any item except Tobacco; for Tobacco, "Yes" to at least one item on the TAPS-2 for Tobacco
  * Alcohol Use Disorders Identification Test (AUDIT-C): score ≥4 (men), ≥3 (women)
  * Modified Brief Pain Inventory (mBPI): "Yes" to at least one of the following:

    * Over the past 24 hours have you needed to take your pain medication to help you sleep?
    * Have you taken any pain medications for any reason other than your pain, such as to reduce anxiety or improve mood?
    * Have you taken more pain medication than was prescribed to you in the past 24 hours?
* At the Post-Operative Call (7-13 days post-op): Postoperative daily opioid dose ≥ preoperative daily opioid dose (identified during the Pre-Surgery Call 5-1 day before surgery), measured in Morphine Milligram Equivalents (MME).

EXCLUSION CRITERIA

* Infection, tumor, or fracture at the operative site
* Allergy or intolerance to tizanidine
* Current use of tizanidine
* Renal impairment (Creatinine Clearance \[CrCl\] \< 25 ml/min)
* Hepatic impairment, including cirrhosis or elevated liver 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
* Planned cancer treatment in the \< 3 months following surgery
* Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status)
* Participating in another clinical trial with an active treatment arm

Where this trial is running

Stanford, California and 3 other locations

• Stanford University Medical Center — Stanford, California, United States (Recruiting)
• University of Kansas Medical Center — Kansas City, Kansas, United States (Recruiting)
• Harvard University- Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• Atrium Health Wake Forest Baptist Medical Center — Winston-Salem, North Carolina, United States (Recruiting)

Study contacts

• Study coordinator: Shana C Levine, BA, CARES RESEARCH COORDINATOR

Conditions Chronic Pain; Back Pain; Neck Pain; Opioid Misuse