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

Phase 3RecruitingNCT06027099

Stanford University375 enrolled

Overview

The goal of this clinical trial is to learn whether a combined behavioral and pharmacologic intervention can help reduce opioid use, improve pain recovery, and prevent opioid misuse after surgery in adults undergoing elective surgery. The study includes adults aged 18 to 75 who have a history of long-term opioid use, defined as having access to opioids for 60 or more days within the 180 days before surgery. The main questions it aims to answer are: * Does Motivational Interviewing with guided opioid tapering plus tizanidine (MI-Opioid Taper + Tizanidine) help participants return to their preoperative opioid use level or stop opioids faster than Enhanced Usual Care (EUC)? * Does the intervention reduce the time to pain resolution and decrease the likelihood of opioid misuse after surgery compared to EUC? Researchers will compare MI-Opioid Taper + Tizanidine to MI-Opioid Taper with placebo and to EUC to see whether the intervention improves postoperative opioid and pain outcomes. Participants will: * Complete a phone assessment and baseline survey before surgery * Be randomly assigned 7-13 days after surgery to one of three groups: * MI-Opioid Taper + tizanidine (MTT) * MI-Opioid Taper + placebo (MTP) * Enhanced Usual Care (EUC) * Complete brief weekly phone or video visits with a study clinician for 6 weeks starting 14 days after surgery * Take a study medication (tizanidine or placebo) three times daily for 5 weeks (MTT and MTP groups only) * Complete weekly online surveys for 6 months, followed by monthly surveys until 12 months after surgery to track pain, opioid use, and related outcomes

This is a Type 1 hybrid effectiveness-implementation, three-arm, parallel randomized controlled trial (RCT) evaluating a behavioral-pharmacologic intervention for postoperative opioid management in patients with preoperative long-term opioid use (LTOU). A total of 375 participants will be enrolled across four academic medical centers: * Stanford University Medical Center, * Harvard University- Brigham and Women's Hospital, * Wake Forest University- Atrium Health Wake Forest Baptist Medical Center, and * University of Kansas Medical Center. Eligible participants will be randomized in equal allocation to one of three study conditions: * Motivational Interviewing-Guided Opioid Taper combined with tizanidine (MI-Opioid Taper + Tizanidine), * MI-Opioid Taper with placebo, or * Enhanced Usual Care (EUC). Participants will be followed for 12 months following surgery, with structured assessments of opioid use, pain outcomes, and related behavioral and clinical measures. The primary endpoint is time to return to baseline opioid use. Secondary endpoints include time to opioid cessation, time to opioid dispensing cessation, time to pain cessation, and incidence of postoperative opioid misuse. Additional exploratory analyses will examine behavioral and clinical mediators of treatment effects, including motivation for change, change talk, and pain reduction. Effect modification analyses will assess whether baseline participant characteristics are associated with differential treatment engagement and outcomes. Implementation outcomes will be evaluated using a mixed-methods approach guided by the RE-AIM framework, focusing on barriers and facilitators to future dissemination and scalability of the MI-Opioid Taper intervention. This project addresses a critical gap in postoperative care for patients with long-term opioid use in need of precision postoperative pain care to minimize opioid-related harms.

Interventions

TizanidineDRUG

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

MI-Opioid TaperBEHAVIORAL

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.

PlaceboDRUG

1 tablet three times a day for 5 weeks after surgery

Enhanced Usual CareBEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (4)

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

Outcomes

Primary Outcomes

Time to Baseline Opioid Use

Defined as the first of two consecutive reports of return to preoperative daily MME or lower on the modified Brief Pain Inventory (mBPI) or the Recent Opioid Medication Use survey. Preoperative daily MME use is defined as average daily MME assessed during the Preoperative Call in the 1-5 day window prior to surgery.

Time frame: From Postoperative Day 7 through Postoperative Day 365

Secondary Outcomes

Time to Complete Opioid Cessation

First of two consecutive reports of opioid cessation on the modified Brief Pain Inventory (mBPI) or the Recent Opioid Medication Use survey.

Time frame: From Postoperative Day 7 through Postoperative Day 365

Time to Opioid Dispensing Cessation

Via state Prescription Drug Monitoring Program (PDMP): First day in the first gap in opioid prescribing ≥ 30 days after surgery

Time frame: From Postoperative Day 7 through Postoperative Day 365

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

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts