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

NCT06027099 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 71909
• Study Type: interventional
• Target: 375
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Chronic Pain; Back Pain; Neck Pain; Opioid Misuse

Outcome Measures

Primary Outcomes (1)

• 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.

  From Postoperative Day 7 through Postoperative Day 365

Secondary Outcomes (2)

• Time to Complete Opioid Cessation

  From Postoperative Day 7 through Postoperative Day 365

• Time to Opioid Dispensing Cessation

  From Postoperative Day 7 through Postoperative Day 365

Study Arms (3)

MI-Opioid Taper and tizanidine

EXPERIMENTAL

Drug: Tizanidine; Behavioral: MI-Opioid Taper

MI-Opioid Taper and placebo

EXPERIMENTAL

Behavioral: MI-Opioid Taper; Drug: Placebo

Enhanced Usual Care

ACTIVE COMPARATOR

Behavioral: Enhanced Usual Care

Interventions

Enhanced Usual Care 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.

Enhanced Usual Care

Tizanidine DRUG

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

MI-Opioid Taper and tizanidine

MI-Opioid Taper 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; MI-Opioid Taper and tizanidine

Placebo DRUG

1 tablet three times a day for 5 weeks after surgery

MI-Opioid Taper and placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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?

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (4)

Stanford University Medical Center

Stanford, California, 94305, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

RECRUITING

Harvard University- Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Atrium Health Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain; Back Pain; Neck Pain; Opioid-Related Disorders

Interventions

tizanidine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Central Study Contacts

Shana C Levine, BA, CARES RESEARCH COORDINATOR

CONTACT

650-649-9618; Shana8@stanford.edu

SPARKLE (Strategies for Pain Alleviation though Research and Knowledge for Long-term Efficacy) Lab

CONTACT

CARESStudy@Stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: September 7, 2023
• Study Start: December 5, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (4)