xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06027099</url>
    </required_header>
    <id_info>
      <org_study_id>71909</org_study_id>
      <nct_id>NCT06027099</nct_id>
    </id_info>
    <brief_title>CARES-Spine (Comprehensive Analgesic, Recovery, and Education Support for Spine Surgery) Trial</brief_title>
    <official_title>Integrating Tailored Postoperative Opioid Tapering and Pain Management Support for Patients on Long-Term Opioid Use Presenting for Spine Surgery</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Stanford University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Stanford University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Three-arm randomized controlled trial, of Motivational Interviewing and guided Opioid&#xD;
        Tapering support (MI-Opioid Taper) and tizanidine vs. MI-Opioid Taper and placebo vs.&#xD;
        enhanced usual care to promote postoperative opioid cessation and pain cessation and reduce&#xD;
        the incidence of postoperative opioid misuse among patients undergoing spine surgery.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this Type 1 hybrid effectiveness-implementation three-arm parallel RCT, 375 patients with&#xD;
        preoperative LTOU undergoing spine surgery will be recruited across 4 sites (Stanford,&#xD;
        Harvard, Wake Forest, U. of Kansas) and randomized to 1 of 3 groups (MI-Opioid Taper and&#xD;
        tizanidine, MI-Opioid Taper and placebo, enhanced usual care) and followed for 12 months. The&#xD;
        primary outcome is time to baseline opioid use. Secondary outcomes are time to opioid&#xD;
        cessation, opioid dispensing cessation, pain cessation, and risk of postoperative opioid&#xD;
        misuse. We will examine motivation for change, change talk, and reduction in pain as&#xD;
        mediators of treatment effects and characterize treatment interactions with participant&#xD;
        attributes in predicting both treatment engagement and efficacy. A mixed-methods evaluation&#xD;
        using the RE-AIM framework will explore barriers and facilitators to future larger-scale&#xD;
        implementation of MI-Opioid Taper. The project will address the unmet needs of patients on&#xD;
        long-term opioid use presenting for surgery in need of precision postoperative pain care to&#xD;
        minimize opioid-related harms.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">February 2024</start_date>
    <completion_date type="Anticipated">July 2028</completion_date>
    <primary_completion_date type="Anticipated">January 2028</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Time to baseline opioid use</measure>
      <time_frame>Assessed after surgery up to 1 year after surgery</time_frame>
      <description>Defined as the 1st of 2 consecutive reports of return to preoperative daily OME use or lower on the modified BPI.Preoperative daily OME use is defined as average daily OME assessed over 3 days, on days 7 to 9 before surgery.</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">375</enrollment>
    <condition>Chronic Pain</condition>
    <condition>Back Pain</condition>
    <condition>Neck Pain</condition>
    <condition>Opioid Misuse</condition>
    <arm_group>
      <arm_group_label>MI-Opioid Taper and tizanidine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>MI-Opioid Taper and placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Enhanced Usual Care</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tizanidine</intervention_name>
      <description>Tizanidine 2mg three times a day for 5 weeks after surgery</description>
      <arm_group_label>MI-Opioid Taper and tizanidine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>MI-Opioid Taper</intervention_name>
      <description>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.</description>
      <arm_group_label>MI-Opioid Taper and placebo</arm_group_label>
      <arm_group_label>MI-Opioid Taper and tizanidine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>1 tablet three times a day for 5 weeks after surgery</description>
      <arm_group_label>MI-Opioid Taper and placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Enhanced Usual Care</intervention_name>
      <description>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 &amp; 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.</description>
      <arm_group_label>Enhanced Usual Care</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults aged 18-64 scheduled for elective spine surgery for lumbar or cervical&#xD;
               degenerative disease (e.g. lumbar or cervical disc herniation, lumbar or cervical&#xD;
               spinal stenosis, lumbar or cervical degenerative spondylolisthesis, lumbar or cervical&#xD;
               disc degeneration, or degenerative cervical myelopathy including cervical spondylotic&#xD;
               myelopathy).&#xD;
  &#xD;
                 -  Preoperative long-term opioid use (Defined as ≥ 90-day duration of use in the 4&#xD;
                    months preceding surgery either via self-report or state PDMP.&#xD;
  &#xD;
                 -  Participants must report at least one of the following on preoperative&#xD;
                    assessments:&#xD;
  &#xD;
          Current Opioid Misuse Measure (COMM) score greater than or equal to 9 Answering &quot;Yes&quot; to&#xD;
          any of the following items on the modified Brief Pain Inventory (BPI)1) Over the past 24&#xD;
          hours have you needed to take your pain medication to help you sleep; 2)Have you taken any&#xD;
          pain medications for any reason other than your pain, such as to reduce anxiety or improve&#xD;
          mood? 3) Have you taken more pain medication than was prescribed to you in the past 24&#xD;
          hours? Score of greater than or equal to 2 on any Tobacco, Alcohol, Prescription&#xD;
          medication, and other Substance use (TAPS-1) item Positive Alcohol Use Disorders&#xD;
          Identification Test (AUDIT-C) score (greater than or equal to 4 for men, greater than or&#xD;
          equal to 3 for women)&#xD;
  &#xD;
            -  Elevated opioid use 14 days after surgery compared to baseline daily OME Defined as&#xD;
               average daily OME assessed over 3 days 1 week before surgery compared to average daily&#xD;
               OME reported on postoperative days 12 to 14 to account for as-needed dosing and&#xD;
               day-to-day variations in opioid use.&#xD;
  &#xD;
            -  English-speaking&#xD;
  &#xD;
            -  Ability and willingness to complete online assessments&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Infection, tumor, or fracture at the operative site&#xD;
  &#xD;
            -  Allergy or intolerance to tizanidine&#xD;
  &#xD;
            -  Current use of tizanidine&#xD;
  &#xD;
            -  Renal impairment&#xD;
  &#xD;
            -  Hepatic impairment including cirrhosis or elevated enzymes&#xD;
  &#xD;
            -  Concurrent use of other α2-adrenergic agonists, skeletal muscle relaxants&#xD;
  &#xD;
            -  Concurrent use of: fluvoxamine, ciprofloxacin,zileuton, fluoroquinolones,&#xD;
               antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine,&#xD;
               famotidine, oral contraceptive pills, acyclovir, ticlopidine, and fexinidazole&#xD;
  &#xD;
            -  Pre-existing hypotension, sedation, dizziness, severe respiratory insufficiency.&#xD;
  &#xD;
            -  Opioid Use Disorder&#xD;
  &#xD;
            -  Suicidality as assessed by the Patient Health Questionnaire-9 (PHQ-9) Question 9 score&#xD;
               ≥ 1&#xD;
  &#xD;
            -  Pregnancy, breastfeeding, or planning to conceive&#xD;
  &#xD;
            -  Cancer diagnosis, active malignant neoplasm (metastatic or local) or evidence of&#xD;
               paraneoplastic syndrome&#xD;
  &#xD;
            -  Conditions causing inability to complete assessments (education, cognitive ability,&#xD;
               mental status, medical status)&#xD;
  &#xD;
            -  Participating in another clinical trial with an active treatment arm&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>64 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Stanford University</investigator_affiliation>
      <investigator_full_name>Jennifer Hah</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Chronic Pain</mesh_term>
      <mesh_term>Neck Pain</mesh_term>
      <mesh_term>Opioid-Related Disorders</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tizanidine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06027099
  org study id: 71909
  nct id: NCT06027099
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  Three-arm randomized controlled trial, of Motivational Interviewing and guided Opioid
        Tapering support (MI-Opioid Taper) and tizanidine vs. MI-Opioid Taper and placebo vs.
        enhanced usual care to promote postoperative opioid cessation and pain cessation and reduce
        the incidence of postoperative opioid misuse among patients undergoing spine surgery.
  In this Type 1 hybrid effectiveness-implementation three-arm parallel RCT, 375 patients with
        preoperative LTOU undergoing spine surgery will be recruited across 4 sites (Stanford,
        Harvard, Wake Forest, U. of Kansas) and randomized to 1 of 3 groups (MI-Opioid Taper and
        tizanidine, MI-Opioid Taper and placebo, enhanced usual care) and followed for 12 months. The
        primary outcome is time to baseline opioid use. Secondary outcomes are time to opioid
        cessation, opioid dispensing cessation, pain cessation, and risk of postoperative opioid
        misuse. We will examine motivation for change, change talk, and reduction in pain as
        mediators of treatment effects and characterize treatment interactions with participant
        attributes in predicting both treatment engagement and efficacy. A mixed-methods evaluation
        using the RE-AIM framework will explore barriers and facilitators to future larger-scale
        implementation of MI-Opioid Taper. The project will address the unmet needs of patients on
        long-term opioid use presenting for surgery in need of precision postoperative pain care to
        minimize opioid-related harms.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Time to baseline opioid use
  time frame: Assessed after surgery up to 1 year after surgery
  description: Defined as the 1st of 2 consecutive reports of return to preoperative daily OME use or lower on the modified BPI.Preoperative daily OME use is defined as average daily OME assessed over 3 days, on days 7 to 9 before surgery.
  arm group label: MI-Opioid Taper and tizanidine
  arm group type: Experimental
  arm group label: MI-Opioid Taper and placebo
  arm group type: Experimental
  arm group label: Enhanced Usual Care
  arm group type: Active Comparator
  intervention type: Drug
  intervention name: Tizanidine
  description: Tizanidine 2mg three times a day for 5 weeks after surgery
  arm group label: MI-Opioid Taper and tizanidine
  intervention type: Behavioral
  intervention name: MI-Opioid Taper
  description: 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.
  arm group label: MI-Opioid Taper and placebo
  arm group label: MI-Opioid Taper and tizanidine
  intervention type: Drug
  intervention name: Placebo
  description: 1 tablet three times a day for 5 weeks after surgery
  arm group label: MI-Opioid Taper and placebo
  intervention type: Behavioral
  intervention name: Enhanced Usual Care
  description: 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.
  arm group label: Enhanced Usual Care
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 64 Years
  healthy volunteers: No
  responsible party type: Principal Investigator
  investigator affiliation: Stanford University
  investigator full name: Jennifer Hah
  investigator title: Associate Professor
  mesh term: Chronic Pain
  mesh term: Neck Pain
  mesh term: Opioid-Related Disorders
  mesh term: Tizanidine