<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/NCT03756961</url>
  </required_header>
  <id_info>
    <org_study_id>OS-PCC-2017</org_study_id>
    <secondary_id>2017-003830-97</secondary_id>
    <nct_id>NCT03756961</nct_id>
  </id_info>
  <brief_title>Effects of an Opioid Free/Sparing Care Pathway for Patients Undergoing Obesity Surgery</brief_title>
  <acronym>OS-PCC</acronym>
  <official_title>Effects of an Opioid Sparing Care Pathway for Patients Undergoing Obesity Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Göteborg University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Göteborg University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The opioid consumption has exploded in the western world, and for some patient populations&#xD;
      such as obese patients, patients with sleep apnoea or patients undergoing cancer treatment,&#xD;
      opioid-sparing/ opioid-free strategies could have positive effects on outcomes. Studies&#xD;
      suggest that opioids could have opioid-induced immunosuppression, induce chronic&#xD;
      post-operative pain syndrome and hyperalgesia in addition to the more well-known side effects&#xD;
      such as respiratory depression, nausea, bladder, and bowel dysfunction. Hence, new studies&#xD;
      are needed on the impact of person-centered care programs that combine pharmaceutical and&#xD;
      non-pharmaceutical strategies to reduce the adverse short and long-term effects of opioid&#xD;
      therapy.&#xD;
&#xD;
      The overall aim is to evaluate the short-, medium- and long-term effects of opioid-free care&#xD;
      pathways with or without person-centred care compared to conventional opioid-based treatment&#xD;
      in patients undergoing obesity surgery.&#xD;
&#xD;
      Specific aims&#xD;
&#xD;
        1. Determine the effects of opioid-free care with or without person-centred care compared&#xD;
           with conventional opioid-based general anaesthesia on the cognitive and physical quality&#xD;
           of recovery after surgery up to 24 months after surgery (short-term: postoperative to&#xD;
           discharge, medium-term: 14 days, 3 months, long-term: 6 months, 12 months and 24&#xD;
           months).&#xD;
&#xD;
        2. Describe the clinical monitoring trend regarding nociceptive response intraoperatively&#xD;
           between opioid-free and conventional care.&#xD;
&#xD;
        3. Map the impact of opioid-free anaesthesia (with and without person-centred care) on the&#xD;
           usage of opioids up to 24 months after hospital discharge.&#xD;
&#xD;
        4. Explore the patients' experience of quality of life, self-efficacy and recovery after&#xD;
           surgery in opioid-free care with or without person-centred care during the first year&#xD;
           post-surgery.&#xD;
&#xD;
      The aims will be evaluated by a prospective, randomized, non-blinded, non-commercial&#xD;
      multi-centre study (Nov 2018-Dec 2022) approved by the Swedish Medicines Agency (EudraCT&#xD;
      2017003830-97) and the ethical review board (DNR 1006-17).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim To evaluate the effects of opioid sparing care pathways compared to conventional&#xD;
      opioid-based treatment for pain relief, opioid consumption, recovery after surgery,&#xD;
      self-efficacy and health economy in patients undergoing obesity surgery. The aim will be&#xD;
      investigated by a prospective, randomized, non-blinded, non-commercial multi-centre study(Nov&#xD;
      2018-Dec 2022), approved by the Swedish Medicines Agency (EudraCT 2017003830-97) and the&#xD;
      ethical review board (DNR 1006-17).&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      1. An opioid-free care pathway provides non-inferior pain relief as the conventional care&#xD;
      with opioids during the post-operative phase.&#xD;
&#xD;
      Primary endpoints: Determine the quality of recovery after surgery&#xD;
&#xD;
        1. No difference in pain (NRS pain (0-10)) between opioid-free intervention with or without&#xD;
           (Phase 1 &amp; 2) person-centred care and conventional treatment (control group) during the&#xD;
           postoperative phase until discharge to the surgical ward.&#xD;
&#xD;
        2. An opioid-free intervention with or without (Phases 1 &amp; 2) person-centred care improves&#xD;
           recovery after surgery measured with the PostopQRS compared with conventional&#xD;
           postoperative therapy, during hospitalisation and afterwards .&#xD;
&#xD;
           Explorative endpoints&#xD;
&#xD;
        3. Describe the intraoperative nociception level between opioid-free anaesthesia and&#xD;
           conventional anaesthesia using the Medasense PMD-200 (NOL) monitor.&#xD;
&#xD;
        4. Map the long-term prescription of opioids and analgesic drugs between the intervention&#xD;
           group and the control group.&#xD;
&#xD;
        5. Explore the patients' experiences with opioid-free intervention with or without&#xD;
           person-centred care with conventional care regarding:&#xD;
&#xD;
             1. self-efficacy measured with the General Self-Efficacy Scale (three months, six&#xD;
                months, 12 months, 24 months).&#xD;
&#xD;
             2. quality of life measured with the RAND-36 and EQ5D (three months, six months, 12&#xD;
                months, 24 months)&#xD;
&#xD;
             3. patient experience and satisfaction, measured with the PostopQRS and interviews&#xD;
                (two weeks, three months, 12 months)&#xD;
&#xD;
      Power Pain: To determine noninferiority with a power of 0.8 (i.e., the probability of &gt; 0.8&#xD;
      for the lower limit of a two-sided 95% confidence interval (using Fisher's nonparametric&#xD;
      permutation test)), the difference of change in pain using the NRS from arrival to the&#xD;
      recovery unit after surgery to discharge from the recovery unit will be used. Forty-three&#xD;
      patients are required in each group and phase, with an SD for the change in the NRS estimated&#xD;
      to be 1.62 from a small pilot study (noninferiority margin -1.0). The estimated change was&#xD;
      assumed to be equal in the groups. To compensate for a potential interruption in the study or&#xD;
      dropouts, we chose to include 55 patients in Intervention Phase 1, 55 patients in&#xD;
      Intervention Phase 2 and a total of 110 patients in the control group (to follow intervention&#xD;
      Phases 1 and 2, each 55 patients).&#xD;
&#xD;
      Recovery after surgery: To detect an overall difference in the quality of recovery between&#xD;
      groups over the entire study length, with a power of 0.8 and P &lt; 0.05 and taking into&#xD;
      consideration a dropout of over 30% as seen in other studies using the PQRS, we need to&#xD;
      include at least 30 patients in each group 26.&#xD;
&#xD;
      The control group will receive usual care and treatment according to the hospital's routines,&#xD;
      where pain relief is obtained with opioids postoperatively. Pharmacological treatment in the&#xD;
      intervention group differs solely from the patients in the usual group by replacing opioids&#xD;
      with the following nonopioid perioperative treatment: dexmedetomidine, esketamine, lidocaine&#xD;
      and TENS (for exact dosing, please visit ClinicalTrials.gov identifier: NCT03756961).&#xD;
      Postoperative patient-controlled pain treatment with high-intensity/high-frequency TENS is&#xD;
      used if the patient perceives pain over NRS ≧ 3 postoperatively and during remaining&#xD;
      hospitalisation.&#xD;
&#xD;
      Intervention Phase 1 tests the pharmacological and non-pharmacological interventions (TENS)&#xD;
      compared to the control group that receives standard care with opioids intra- and&#xD;
      postoperatively. Phase 2 intervention that follows after completion of Phase 1 intervention&#xD;
      tests the pharmacological and nonpharmacological interventions compared to conventional&#xD;
      treatment, supplemented by an evidenced-based PCC approach throughout the continuum of&#xD;
      postoperative care.&#xD;
&#xD;
      The two phases will primarily be analysed separately (i.e., between the control group and&#xD;
      intervention Phase 1 and between the control group and intervention Phase 2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Prospective, randomized, non-blinded, non-commercial multi centre study. The intervention is divided into 2 phases, and the two phases will primarily be analysed separately (i.e., between the control group and intervention Phase 1 and between the control group and intervention Phase 2)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in post-operative pain from admission to the post-anesthesia care unit (PACO) to discharge from the PACO unit to the surgical ward.</measure>
    <time_frame>From date of randomization, difference in NRS will be assessed as the change in NRS from arrival (20 minutes after arrival) to the post-anesthesia care unit(PACU) after the surgery, to the time of discharge ( 4 hour) from the PACU to the surgical ward</time_frame>
    <description>Post-operative phase until discharge to the surgical ward. Pain assessed according to change in NRS (numeric rating scale). NRS (numeric rating scale for pain), (ranging from 0-10, &quot;no pain&quot; vs. &quot;worst imagined pain&quot;).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recovery after surgery</measure>
    <time_frame>(20 min, 40 min), during hospitalization (24 hours-72 hours) and afterwards (14 days, 30 days, three months, six months, 12 months and 24 months)</time_frame>
    <description>Investigating recovery after surgery measured with the The Post-operative Quality of Recovery Scale (PostopQRS) compared with conventional postoperative therapy.&#xD;
PostopQRS: Is a validated 5-dimensional instrument (Physiology, Nociception, Emotion, Cognition, ADL) in addition to questions about patient satisfaction.&#xD;
The scoring of recovery is 'return to baseline values or better' which requires a change score ≥ 0 for each question. The postoperative value for each test ( Cognition has a 2 scale tolerance due to day-to-day variation) is subtracted from the baseline value, and if no difference, then the patient is recovered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average opioid consumption perioperative</measure>
    <time_frame>From the start of the Peri-operative phase (start of surgery) until discharge from hospital ( index stay), up to 24 months post-discharge</time_frame>
    <description>Investigating opioid consumption during the peri- and post-operative care period compared with conventional treatment until discharge from the hospital and up to 24 months discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Indexed length of hospital day will be calculated in days/hours). Estimated stay is 2 days</time_frame>
    <description>Length of indexed hospital stays calculated as the mean length in days from admission to discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in general Self-Efficacy</measure>
    <time_frame>3 months, six months, 12 months, 24 months.</time_frame>
    <description>Investigating patient change in self-efficacy, measured with the General Self-Efficacy Scale (GSES). GSES is a validated questionnaire that contains 10 questions about the person's experiences of trust in his / her ability to handle difficult situations. The patient is asked to estimate his ability on a 4-point scale (1 not true) to 4 (true).&#xD;
The 10 answers are summed and a mean is calculated. Higher scores are better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life</measure>
    <time_frame>(3 months, six months, 12 months, 24 months)</time_frame>
    <description>Investigating the quality of life measured with the RAND-36&#xD;
RAND-36: The RAND-36 is a health-related quality of life (HRQoL) It is comprised of 36 items assessing eight areas: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions.&#xD;
Each item is scored 0-100, and are than summarized. 0 is low, 100 is the highest score to get.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploring patient experience</measure>
    <time_frame>2 weeks after hospital discharge</time_frame>
    <description>Investigating patient experience and satisfaction during the hospital stay, measured with the PPE-15, a 15 item questionnaire. The PPE15 is a validated short version of The Picker Care experience survey (40 item).&#xD;
Each item has response alternatives ranging from no problem, some problem, problem. Each response is coded either as &quot;a problem&quot; ( problem, some problem) or as &quot;no problem&quot;. Problem is scored as=1, no problem=0. The mean is calculated both on item level and as a total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in health status</measure>
    <time_frame>(3 months, six months, 12 months, 24 months)</time_frame>
    <description>Investigating the change in health status measured with the EuroQol 5 dimension (EQ5D).&#xD;
EQ-5D is a standardized instrument for measuring generic health status, covering five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.&#xD;
Each dimension has 3 responses: no problems, some problems, and extreme problems. This response results into a number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.&#xD;
The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned re-admission</measure>
    <time_frame>From time of surgery up until 24 months post-surgery</time_frame>
    <description>Investigating re-admission (un-planned) between groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>From time of surgery up until 24 months post-surgery</time_frame>
    <description>Investigating mortality rate between groups.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">220</enrollment>
  <condition>Obesity</condition>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Control group: The patients receive the routine based anesthesiological treatment during bariatric surgery (Gastric By-Pass or Sleeve Gastrectomy). It consists of:&#xD;
General anesthesia induction: TCI Remifentanil Cpt 6 ng/ml/ Cp 3.2 ng/m, Propofol 1.5-2 mg/kg iv, Desflurane MAC (0.6-0.8).&#xD;
Maintained by Desflurane MAC (0.6-0.8) adjusted via BIS (40-60) and Remifentanil Cp 4-10 ng/ml.&#xD;
Post-operative pain management: Oxycodone 2.5 mg iv if the pain is rated by patient NRS ≧3. Paracetamol 1 g/6 h and Diclofenac 80 mg/24 h.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Induction: Dexmedetomidine 0.2 micrograms/kg/h iv 5 min, Esketamine 0.1mg/kg + Propofol 1.5-2 mg/kg iv, Desflurane MAC (0.6-0.8).&#xD;
Maintained by Desflurane MAC (0.6-0.8) BIS (40-60), Dexmedetomidine 0.2 micrograms/kg/h, Esketamine 0.1-0.3mg/kg/h och 0.1 mg/kg in case of hypertension. At the end of surgery, Lidocaine 1 mg/kg iv (max 4 mg/kg /4 h)&#xD;
Post-operative: Dexmedetomidine (0.1-0.2 micrograms/kg/h up to 4 h post-operative). If the pain is rated NRS ≧3: Transcutaneous Nerve Stimulation (TENS) with high intensive 40-50 mA for 1 minute, if the patient still NRS ≧3, the TENS treatment is repeated one more time. If pain NRS ≧3 after two treatments with TENS: Esketamine 0.1mg/kg iv + Lidocaine 0.5 mg/kg iv (max 4 mg/kg /4 h) If pain NRS still ≧3 within 30 minutes after both TENS and Esketamine/Lidocaine, 2.5 mg Oxycodone iv, with a 10 minutes intervals until NRS &lt; 3. Perioperative and at discharge, PCC will be used for the the intervention (Phase 2 patients)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>The intervention group will obtain the pharmacological treatment during both perioperative. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment:</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Dexdor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Person-centred care (PCC)</intervention_name>
    <description>The intervention tests non-pharmacological interventions compared to conventional treatment, supplemented by an evidenced-based Person-centred care PCC approach throughout the continuum of the perioperative and until 4 weeks after discharge. This will be part of patients in Phase 2</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Phase 2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>The intervention group will obtain the pharmacological treatment perioperatively. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment:</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Ketanest</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine</intervention_name>
    <description>The intervention group will obtain the pharmacological treatment perioperatively. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment.</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Xylocaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcutaneous Nerve Stimulation (TENS)</intervention_name>
    <description>The intervention group will obtain non-pharmacological treatment by TENS during the entire hospital stay (both perioperative and post-operative) until discharge.</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>TENS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>The control group receives general anesthesia with Remifentanil as the routine opioid drug during general anesthesia.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Ultiva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Desflurane</intervention_name>
    <description>The patient receives general anesthesia with Desflurane as the routine volatile anesthetic during general anesthesia</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Desfluran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>The patient receives general anesthesia with Propofol as the routine induction anaesthetic during general anesthesia</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxycodone</intervention_name>
    <description>The control group receives Oxycodone as the routine pain management drug post-operative.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -Patients ≥18 years planned to undergo laparoscopic obesity surgery (GBP alt Sleeve&#xD;
        surgery) at the selected site.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ASA&gt; III&#xD;
&#xD;
          -  Cardiovascular disease with bradycardia (&lt;50 bpm)&#xD;
&#xD;
          -  Serious liver disease failure&#xD;
&#xD;
          -  Insufficient knowledge of the Swedish language&#xD;
&#xD;
          -  Serious untreated psychiatric disease&#xD;
&#xD;
          -  Neurocognitive dysfunction&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Women of childbearing age without contraception&#xD;
&#xD;
          -  Malignant disease with expected short survival&#xD;
&#xD;
          -  Patients treated with opioids for chronic pain&#xD;
&#xD;
          -  Substance abuse&#xD;
&#xD;
          -  Hypersensitivity to Oxycodone, Esketamine, Dexmedetomidine, and Lidocaine&#xD;
&#xD;
          -  Pacemaker or ICD&#xD;
&#xD;
          -  Inability to fill in questionnaires&#xD;
&#xD;
          -  Decline participation,&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sven-Egron Thörn, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Göteborg University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Axel Wolf, RN, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Göteborg University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Axel Wolf, RN, PhD</last_name>
    <phone>0046317866034</phone>
    <email>axel.wolf@gu.se</email>
  </overall_contact>
  <location>
    <facility>
      <name>Lindesberg Hospital</name>
      <address>
        <city>Lindesberg</city>
        <state>Region Örebro</state>
        <zip>711 82</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Henrik Öhström, MD</last_name>
      <phone>+4619-602 03 56‬</phone>
      <email>henrik.ohrstrom@regionorebrolan.se</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska University hospital/ Östra hopsital</name>
      <address>
        <city>Gothenburg</city>
        <state>VG</state>
        <zip>41678</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Axel Wolf, RN/MBA/PhD</last_name>
      <phone>+46709355364</phone>
      <email>axel.wolf@gu.se</email>
    </contact>
    <contact_backup>
      <last_name>Sven-Egron Thörn, MD/PhD</last_name>
      <phone>+46 31-343 49 03</phone>
      <email>sven-egron.thorn@vgregion.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>opioids</keyword>
  <keyword>bariatric surgery</keyword>
  <keyword>anesthesia</keyword>
  <keyword>opioid-free</keyword>
  <keyword>person-centred care</keyword>
  <keyword>recovery</keyword>
  <keyword>TENS</keyword>
  <keyword>pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Dexmedetomidine</mesh_term>
    <mesh_term>Remifentanil</mesh_term>
    <mesh_term>Oxycodone</mesh_term>
    <mesh_term>Propofol</mesh_term>
    <mesh_term>Desflurane</mesh_term>
    <mesh_term>Esketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03756961
org study id: OS-PCC-2017
secondary id: 2017-003830-97
nct id: NCT03756961
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The opioid consumption has exploded in the western world, and for some patient populations
      such as obese patients, patients with sleep apnoea or patients undergoing cancer treatment,
      opioid-sparing/ opioid-free strategies could have positive effects on outcomes. Studies
      suggest that opioids could have opioid-induced immunosuppression, induce chronic
      post-operative pain syndrome and hyperalgesia in addition to the more well-known side effects
      such as respiratory depression, nausea, bladder, and bowel dysfunction. Hence, new studies
      are needed on the impact of person-centered care programs that combine pharmaceutical and
      non-pharmaceutical strategies to reduce the adverse short and long-term effects of opioid
      therapy.

      The overall aim is to evaluate the short-, medium- and long-term effects of opioid-free care
      pathways with or without person-centred care compared to conventional opioid-based treatment
      in patients undergoing obesity surgery.

      Specific aims

        1. Determine the effects of opioid-free care with or without person-centred care compared
           with conventional opioid-based general anaesthesia on the cognitive and physical quality
           of recovery after surgery up to 24 months after surgery (short-term: postoperative to
           discharge, medium-term: 14 days, 3 months, long-term: 6 months, 12 months and 24
           months).

        2. Describe the clinical monitoring trend regarding nociceptive response intraoperatively
           between opioid-free and conventional care.

        3. Map the impact of opioid-free anaesthesia (with and without person-centred care) on the
           usage of opioids up to 24 months after hospital discharge.

        4. Explore the patients' experience of quality of life, self-efficacy and recovery after
           surgery in opioid-free care with or without person-centred care during the first year
           post-surgery.

      The aims will be evaluated by a prospective, randomized, non-blinded, non-commercial
      multi-centre study (Nov 2018-Dec 2022) approved by the Swedish Medicines Agency (EudraCT
      2017003830-97) and the ethical review board (DNR 1006-17).
Aim To evaluate the effects of opioid sparing care pathways compared to conventional
      opioid-based treatment for pain relief, opioid consumption, recovery after surgery,
      self-efficacy and health economy in patients undergoing obesity surgery. The aim will be
      investigated by a prospective, randomized, non-blinded, non-commercial multi-centre study(Nov
      2018-Dec 2022), approved by the Swedish Medicines Agency (EudraCT 2017003830-97) and the
      ethical review board (DNR 1006-17).

      Hypothesis

      1. An opioid-free care pathway provides non-inferior pain relief as the conventional care
      with opioids during the post-operative phase.

      Primary endpoints: Determine the quality of recovery after surgery

        1. No difference in pain (NRS pain (0-10)) between opioid-free intervention with or without
           (Phase 1 & 2) person-centred care and conventional treatment (control group) during the
           postoperative phase until discharge to the surgical ward.

        2. An opioid-free intervention with or without (Phases 1 & 2) person-centred care improves
           recovery after surgery measured with the PostopQRS compared with conventional
           postoperative therapy, during hospitalisation and afterwards .

           Explorative endpoints

        3. Describe the intraoperative nociception level between opioid-free anaesthesia and
           conventional anaesthesia using the Medasense PMD-200 (NOL) monitor.

        4. Map the long-term prescription of opioids and analgesic drugs between the intervention
           group and the control group.

        5. Explore the patients' experiences with opioid-free intervention with or without
           person-centred care with conventional care regarding:

             1. self-efficacy measured with the General Self-Efficacy Scale (three months, six
                months, 12 months, 24 months).

             2. quality of life measured with the RAND-36 and EQ5D (three months, six months, 12
                months, 24 months)

             3. patient experience and satisfaction, measured with the PostopQRS and interviews
                (two weeks, three months, 12 months)

      Power Pain: To determine noninferiority with a power of 0.8 (i.e., the probability of > 0.8
      for the lower limit of a two-sided 95% confidence interval (using Fisher's nonparametric
      permutation test)), the difference of change in pain using the NRS from arrival to the
      recovery unit after surgery to discharge from the recovery unit will be used. Forty-three
      patients are required in each group and phase, with an SD for the change in the NRS estimated
      to be 1.62 from a small pilot study (noninferiority margin -1.0). The estimated change was
      assumed to be equal in the groups. To compensate for a potential interruption in the study or
      dropouts, we chose to include 55 patients in Intervention Phase 1, 55 patients in
      Intervention Phase 2 and a total of 110 patients in the control group (to follow intervention
      Phases 1 and 2, each 55 patients).

      Recovery after surgery: To detect an overall difference in the quality of recovery between
      groups over the entire study length, with a power of 0.8 and P < 0.05 and taking into
      consideration a dropout of over 30% as seen in other studies using the PQRS, we need to
      include at least 30 patients in each group 26.

      The control group will receive usual care and treatment according to the hospital's routines,
      where pain relief is obtained with opioids postoperatively. Pharmacological treatment in the
      intervention group differs solely from the patients in the usual group by replacing opioids
      with the following nonopioid perioperative treatment: dexmedetomidine, esketamine, lidocaine
      and TENS (for exact dosing, please visit ClinicalTrials.gov identifier: NCT03756961).
      Postoperative patient-controlled pain treatment with high-intensity/high-frequency TENS is
      used if the patient perceives pain over NRS ≧ 3 postoperatively and during remaining
      hospitalisation.

      Intervention Phase 1 tests the pharmacological and non-pharmacological interventions (TENS)
      compared to the control group that receives standard care with opioids intra- and
      postoperatively. Phase 2 intervention that follows after completion of Phase 1 intervention
      tests the pharmacological and nonpharmacological interventions compared to conventional
      treatment, supplemented by an evidenced-based PCC approach throughout the continuum of
      postoperative care.

      The two phases will primarily be analysed separately (i.e., between the control group and
      intervention Phase 1 and between the control group and intervention Phase 2).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, randomized, non-blinded, non-commercial multi centre study. The intervention is divided into 2 phases, and the two phases will primarily be analysed separately (i.e., between the control group and intervention Phase 1 and between the control group and intervention Phase 2)
primary purpose: Treatment
masking: None (Open Label)
measure: Difference in post-operative pain from admission to the post-anesthesia care unit (PACO) to discharge from the PACO unit to the surgical ward.
time frame: From date of randomization, difference in NRS will be assessed as the change in NRS from arrival (20 minutes after arrival) to the post-anesthesia care unit(PACU) after the surgery, to the time of discharge ( 4 hour) from the PACU to the surgical ward
description: Post-operative phase until discharge to the surgical ward. Pain assessed according to change in NRS (numeric rating scale). NRS (numeric rating scale for pain), (ranging from 0-10, "no pain" vs. "worst imagined pain").
measure: Recovery after surgery
time frame: (20 min, 40 min), during hospitalization (24 hours-72 hours) and afterwards (14 days, 30 days, three months, six months, 12 months and 24 months)
description: Investigating recovery after surgery measured with the The Post-operative Quality of Recovery Scale (PostopQRS) compared with conventional postoperative therapy.
PostopQRS: Is a validated 5-dimensional instrument (Physiology, Nociception, Emotion, Cognition, ADL) in addition to questions about patient satisfaction.
The scoring of recovery is 'return to baseline values or better' which requires a change score ≥ 0 for each question. The postoperative value for each test ( Cognition has a 2 scale tolerance due to day-to-day variation) is subtracted from the baseline value, and if no difference, then the patient is recovered.
measure: Average opioid consumption perioperative
time frame: From the start of the Peri-operative phase (start of surgery) until discharge from hospital ( index stay), up to 24 months post-discharge
description: Investigating opioid consumption during the peri- and post-operative care period compared with conventional treatment until discharge from the hospital and up to 24 months discharge.
measure: Length of hospital stay
time frame: Indexed length of hospital day will be calculated in days/hours). Estimated stay is 2 days
description: Length of indexed hospital stays calculated as the mean length in days from admission to discharge
measure: Change in general Self-Efficacy
time frame: 3 months, six months, 12 months, 24 months.
description: Investigating patient change in self-efficacy, measured with the General Self-Efficacy Scale (GSES). GSES is a validated questionnaire that contains 10 questions about the person's experiences of trust in his / her ability to handle difficult situations. The patient is asked to estimate his ability on a 4-point scale (1 not true) to 4 (true).
The 10 answers are summed and a mean is calculated. Higher scores are better.
measure: Change in Quality of Life
time frame: (3 months, six months, 12 months, 24 months)
description: Investigating the quality of life measured with the RAND-36
RAND-36: The RAND-36 is a health-related quality of life (HRQoL) It is comprised of 36 items assessing eight areas: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions.
Each item is scored 0-100, and are than summarized. 0 is low, 100 is the highest score to get.
measure: Exploring patient experience
time frame: 2 weeks after hospital discharge
description: Investigating patient experience and satisfaction during the hospital stay, measured with the PPE-15, a 15 item questionnaire. The PPE15 is a validated short version of The Picker Care experience survey (40 item).
Each item has response alternatives ranging from no problem, some problem, problem. Each response is coded either as "a problem" ( problem, some problem) or as "no problem". Problem is scored as=1, no problem=0. The mean is calculated both on item level and as a total score.
measure: Change in health status
time frame: (3 months, six months, 12 months, 24 months)
description: Investigating the change in health status measured with the EuroQol 5 dimension (EQ5D).
EQ-5D is a standardized instrument for measuring generic health status, covering five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Each dimension has 3 responses: no problems, some problems, and extreme problems. This response results into a number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.
measure: Unplanned re-admission
time frame: From time of surgery up until 24 months post-surgery
description: Investigating re-admission (un-planned) between groups.
measure: Mortality
time frame: From time of surgery up until 24 months post-surgery
description: Investigating mortality rate between groups.
arm group label: Control
arm group type: Active Comparator
description: Control group: The patients receive the routine based anesthesiological treatment during bariatric surgery (Gastric By-Pass or Sleeve Gastrectomy). It consists of:
General anesthesia induction: TCI Remifentanil Cpt 6 ng/ml/ Cp 3.2 ng/m, Propofol 1.5-2 mg/kg iv, Desflurane MAC (0.6-0.8).
Maintained by Desflurane MAC (0.6-0.8) adjusted via BIS (40-60) and Remifentanil Cp 4-10 ng/ml.
Post-operative pain management: Oxycodone 2.5 mg iv if the pain is rated by patient NRS ≧3. Paracetamol 1 g/6 h and Diclofenac 80 mg/24 h.
arm group label: Intervention
arm group type: Experimental
description: Induction: Dexmedetomidine 0.2 micrograms/kg/h iv 5 min, Esketamine 0.1mg/kg + Propofol 1.5-2 mg/kg iv, Desflurane MAC (0.6-0.8).
Maintained by Desflurane MAC (0.6-0.8) BIS (40-60), Dexmedetomidine 0.2 micrograms/kg/h, Esketamine 0.1-0.3mg/kg/h och 0.1 mg/kg in case of hypertension. At the end of surgery, Lidocaine 1 mg/kg iv (max 4 mg/kg /4 h)
Post-operative: Dexmedetomidine (0.1-0.2 micrograms/kg/h up to 4 h post-operative). If the pain is rated NRS ≧3: Transcutaneous Nerve Stimulation (TENS) with high intensive 40-50 mA for 1 minute, if the patient still NRS ≧3, the TENS treatment is repeated one more time. If pain NRS ≧3 after two treatments with TENS: Esketamine 0.1mg/kg iv + Lidocaine 0.5 mg/kg iv (max 4 mg/kg /4 h) If pain NRS still ≧3 within 30 minutes after both TENS and Esketamine/Lidocaine, 2.5 mg Oxycodone iv, with a 10 minutes intervals until NRS < 3. Perioperative and at discharge, PCC will be used for the the intervention (Phase 2 patients)
intervention type: Drug
intervention name: Dexmedetomidine
description: The intervention group will obtain the pharmacological treatment during both perioperative. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment:
arm group label: Intervention
other name: Dexdor
intervention type: Behavioral
intervention name: Person-centred care (PCC)
description: The intervention tests non-pharmacological interventions compared to conventional treatment, supplemented by an evidenced-based Person-centred care PCC approach throughout the continuum of the perioperative and until 4 weeks after discharge. This will be part of patients in Phase 2
arm group label: Intervention
other name: Phase 2
intervention type: Drug
intervention name: Esketamine
description: The intervention group will obtain the pharmacological treatment perioperatively. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment:
arm group label: Intervention
other name: Ketanest
intervention type: Drug
intervention name: Lidocaine
description: The intervention group will obtain the pharmacological treatment perioperatively. Pharmacological treatment in the intervention group differs solely from the patients in the control group by replacing opioids with the following non-opioid treatment.
arm group label: Intervention
other name: Xylocaine
intervention type: Device
intervention name: Transcutaneous Nerve Stimulation (TENS)
description: The intervention group will obtain non-pharmacological treatment by TENS during the entire hospital stay (both perioperative and post-operative) until discharge.
arm group label: Intervention
other name: TENS
intervention type: Drug
intervention name: Remifentanil
description: The control group receives general anesthesia with Remifentanil as the routine opioid drug during general anesthesia.
arm group label: Control
other name: Ultiva
intervention type: Drug
intervention name: Desflurane
description: The patient receives general anesthesia with Desflurane as the routine volatile anesthetic during general anesthesia
arm group label: Control
arm group label: Intervention
other name: Desfluran
intervention type: Drug
intervention name: Propofol
description: The patient receives general anesthesia with Propofol as the routine induction anaesthetic during general anesthesia
arm group label: Control
arm group label: Intervention
intervention type: Drug
intervention name: Oxycodone
description: The control group receives Oxycodone as the routine pain management drug post-operative.
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sven-Egron Thörn, MD, PhD
role: Principal Investigator
affiliation: Göteborg University
last name: Axel Wolf, RN, PhD
role: Principal Investigator
affiliation: Göteborg University
last name: Axel Wolf, RN, PhD
phone: 0046317866034
email: axel.wolf@gu.se
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
responsible party type: Sponsor
mesh term: Obesity
mesh term: Pain, Postoperative
mesh term: Lidocaine
mesh term: Dexmedetomidine
mesh term: Remifentanil
mesh term: Oxycodone
mesh term: Propofol
mesh term: Desflurane
mesh term: Esketamine
sharing ipd: No