Chronic PainPhase 3CARESNCT06027099
CARES (Comprehensive Analgesic, Recovery, and Education Support) for Surgery Trial
A Phase 3 study testing Tizanidine and MI-Opioid Taper in people with Chronic Pain and Back Pain, run by Stanford University at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Pain, Back Pain, Neck Pain
- What is being tested?
- Tizanidine and MI-Opioid Taper
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 375 participants
- Where
- 4 sitesUnited States
- Study dates
- 5 Dec 2024to Jul 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
SPARKLE (Strategies for Pain Alleviation though Research and Knowledge for Long-term Efficacy) Lab contact
United States4 sites, 4 recruiting
- Recruiting
Harvard University- Brigham and Women's Hospital
Boston, Massachusetts, 02115
Samantha Meints, PhD (PRINCIPAL INVESTIGATOR), 612-205-0186, smeints@bwh.harvard.edu
Caroline Allen, BS, 617-732-9014, callen22@bwh.harvard.edu
- Recruiting
University of Kansas Medical Center
Kansas City, Kansas, 66103
Andrea Chadwick, MD, MSc, FASA, 913-588-3479, anicol@kumc.edu
FACE (Fibromyalgia And Centralized pain Exploration) Lab, 913-588-7630, facelab@kumc.edu
- Recruiting
Stanford University Medical Center
Stanford, California, 94305
Jennifer M Hah, MD, MS, 650-724-3193, jhah@stanford.edu
Shana C Levine, BA, 650-649-9618, shana8@stanford.edu
- Recruiting
Atrium Health Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
Robert Hurley, MD, PhD, FASA, 336-716-1228, Robert.Hurley@Advocatehealth.org
Lynnette Harris, RN, BSN, 336-716-8791, Lynnette.Harris@advocatehealth.org
About this study
Official title: Integrating Tailored Postoperative Opioid Tapering and Pain Management Support for Patients on Long-Term Opioid Use Presenting for Surgery
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:
Read more
- 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
Read the detailed description
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.
- Conditions
- Chronic Pain, Back Pain, Neck Pain, Opioid Misuse
- Being tested
- Tizanidine, MI-Opioid Taper, Placebo, Enhanced Usual Care
- Medical subject headings
- Chronic Pain, Back Pain, Neck Pain, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TizanidineDrug
Tizanidine 2mg three times a day for 5 weeks after surgery
MI-Opioid TaperBehavioural
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 CareBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| MI-Opioid Taper and tizanidine | Experimental | Not described Receives: Drug: Tizanidine; Behavioral: MI-Opioid Taper |
| MI-Opioid Taper and placebo | Experimental | Not described Receives: Behavioral: MI-Opioid Taper; Drug: Placebo |
| Enhanced Usual Care | Active comparator | Not described Receives: Behavioral: Enhanced Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Postoperative Day 7 through Postoperative Day 365
Secondary outcomes (2)
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.
Measured: 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
Measured: From Postoperative Day 7 through Postoperative Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2023
- Study start5 Dec 2024
- Primary completionJan 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 375 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Hah, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06027099
- Sponsor's protocol ID
- 71909
- Acronym
- CARES
- Status last verified
- May 2026
- First submitted
- 30 Aug 2023
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Integrating Tailored Postoperative Opioid Tapering and Pain Management Support for Patients on Long-Term Opioid Use Presenting for Surgery
- ClinicalTrials.gov ID
- NCT06027099
- Acronym / sponsor ID
- CARES / 71909
- Conditions
- Chronic Pain, Back Pain, Neck Pain, Opioid Misuse
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 375 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 5 Dec 2024 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 7 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 18 to 75 years of age
- Able to speak, write, and read fluently in English
- Scheduled for elective surgery at
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TizanidineTizanidine 2mg three times a day for 5 weeks after surgery | Drug | MI-Opioid Taper and tizanidine |
| MI-Opioid TaperMotivational 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. | Behavioural | MI-Opioid Taper and placebo, MI-Opioid Taper and tizanidine |
| Placebo1 tablet three times a day for 5 weeks after surgery | Drug | MI-Opioid Taper and placebo |
| Enhanced Usual CareParticipants 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. | Behavioural | Enhanced Usual Care |
Primary outcome
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.
2 secondary outcomes
Time to Complete Opioid Cessation
Time frame: From Postoperative Day 7 through Postoperative Day 365
Time to Opioid Dispensing Cessation
Time frame: From Postoperative Day 7 through Postoperative Day 365
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
SPARKLE (Strategies for Pain Alleviation though Research and Knowledge for Long-term Efficacy) Lab contact
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tizanidine and MI-Opioid Taper in people with Chronic Pain and Back Pain, run by Stanford University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shana C Levine, BA, CARES RESEARCH COORDINATOR (650-649-9618, Shana8@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Baseline Opioid Use (time frame: From Postoperative Day 7 through Postoperative Day 365). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.