NCT06027099 · Stanford University
CARES (Comprehensive Analgesic, Recovery, and Education Support) for Surgery Trial
(CARES)
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Tizanidine
Tizanidine 2mg three times a day for 5 weeks after surgery
BEHAVIORAL
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.
DRUG
Placebo
1 tablet three times a day for 5 weeks after surgery
BEHAVIORAL
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.
Primary outcome measures
Time to Baseline Opioid Use
Time frame: From Postoperative Day 7 through Postoperative Day 365
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
- Stanford, California
- Kansas City, Kansas
- Boston, Massachusetts
- Winston-Salem, North Carolina
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 6, 2026 · Source of record for eligibility and locations