<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/NCT04432428</url>
  </required_header>
  <id_info>
    <org_study_id>2019/1741</org_study_id>
    <nct_id>NCT04432428</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Patient Controlled Analgesia Using the Sublingual Sufentanil Tablet System (SSTS) in a Fast Track Rehabilitation Program After Total Knee Arthroplasty</brief_title>
  <acronym>Zalviso</acronym>
  <official_title>Safety and Efficacy of Patient Controlled Analgesia Using the Sublingual Sufentanil Tablet System (SSTS) in a Fast Track Rehabilitation Program After Total Knee Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Ghent</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Ghent</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 sufentanil sublingual tablet system (SSTS) is an innovative patient-controlled analgesia&#xD;
      (PCA) device for the management of acute moderate to severe postoperative pain in hospital&#xD;
      settings in adult patients.&#xD;
&#xD;
      The SSTS is non-invasive and imposes no restrictions on patient mobility, which renders it&#xD;
      particularly suitable for clinical conditions where early mobilization is a key component of&#xD;
      successful surgical outcome.&#xD;
&#xD;
      The present study tests the hypothesis that SSTS is an efficient and safe analgesic technique&#xD;
      allowing fast track rehabilitation after total knee arthroplasty in a prospective cohort&#xD;
      design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Total knee arthroplasty is one of the most common major procedures performed today with a&#xD;
      significant impact on health care budgets. Fast track rehabilitation programmes are being&#xD;
      developed to control hospitalization costs associated with this procedure. Interestingly,&#xD;
      such pathway controlled fast track programs also appear to enhance functional recovery and to&#xD;
      reduce complications. These beneficial effects are mainly attributed to the practice of rapid&#xD;
      mobilization and early intensified physiotherapy which can only be achieved with effective&#xD;
      analgesic techniques.&#xD;
&#xD;
      Current PCA techniques - predominantly morphine based - are the gold standard for this&#xD;
      purpose but they involve intravenous access and a programmable computer system requiring&#xD;
      close supervision. Reported shortcomings are systems failure leading to analgesic gaps, drug&#xD;
      errors and restrictions in mobility since patients are tethered to IV poles. The SSTS may&#xD;
      overcome these limitations because the opioid used, sufentanil, has a more predictable time&#xD;
      of onset, the delivery system does not require programming, and the device does not limit&#xD;
      patient's mobility. It retains the benefits of potent analgesia as well as patient&#xD;
      empowerment and is particularly suited to target the analgesic effect precisely to the level&#xD;
      required in physiotherapeutic sessions.&#xD;
&#xD;
      The present study will test the hypothesis that SSTS is an efficient and safe analgesic&#xD;
      technique allowing fast track rehabilitation after total knee arthroplasty in a prospective&#xD;
      cohort design.&#xD;
&#xD;
      The study will focus on the efficiency of STSS which is defined as 75% or more of the treated&#xD;
      patients proves NRS score less than 4 during 48 hours postoperatively, additionally to the&#xD;
      basic pain treatment (paracetamol and NSAID).&#xD;
&#xD;
      The STSS will allow the patient tot take a maximum of 3 doses in one hour. Treatment with the&#xD;
      STSS is continued over a period of 48 hours or if necessary up to 72 hours.&#xD;
&#xD;
      During this period the patients pain en parameters will be monitored closely.&#xD;
&#xD;
      The maximum administered total dose of Zalviso will not exceed 1.2mg.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 26, 2020</start_date>
  <completion_date type="Actual">September 19, 2021</completion_date>
  <primary_completion_date type="Actual">August 31, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Multicentric interventional prospective cohort study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total time NRS&lt;4</measure>
    <time_frame>from end of surgery until 48 hours postoperatively</time_frame>
    <description>cumulative time that patient had NRS&lt;4</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>length of hospital stay</measure>
    <time_frame>from hospital admission until hospital discharge, up to 1 week post-operatively</time_frame>
    <description>amount of days that patient was admitted to the hosptial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the side effect nausea</measure>
    <time_frame>from end of surgery until 72 hours postoperatively</time_frame>
    <description>Incidence of the side effect nausea with a simple scale (none, mild, moderate, severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the side effect vomiting</measure>
    <time_frame>from end of surgery until 72 hours postoperatively</time_frame>
    <description>Incidence of the side effect vomiting with a simple scale (none, mild, moderate, severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the side effect itching</measure>
    <time_frame>from end of surgery until 72 hours postoperatively</time_frame>
    <description>Incidence of the side effect itching with a simple scale (none, mild, moderate, severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the side effect drowsiness</measure>
    <time_frame>from end of surgery until 72 hours postoperatively</time_frame>
    <description>Incidence of the side effect drowsiness with a simple scale (none, mild, moderate, severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of the side effect constipation</measure>
    <time_frame>from end of surgery until 72 hours postoperatively</time_frame>
    <description>Incidence of the side effect constipation with a simple scale (none, mild, moderate, severe)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen desaturation</measure>
    <time_frame>from end of surgery until 72 hours postoperatively</time_frame>
    <description>Oxygen desaturation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>patient satisfaction with Zalviso PCA</measure>
    <time_frame>after discontinuation of study medication, up to 72 hrs after start of the study medication</time_frame>
    <description>patient satisfaction assessed with patient ease of care questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>health care worker satisfaction with the patients pain treatment with Zalviso PCA</measure>
    <time_frame>after patients discontinuation of study medication, up to 1 week after stop study medication</time_frame>
    <description>health care worker satisfaction assessed with nurse/physical therapist ease of care questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>consumption of study medication</measure>
    <time_frame>from start administration of study medication until end of administration of study medication, up to a maximum of 72 hrs</time_frame>
    <description>total amount of study medication that was administered</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of analgesia during physiotherapy</measure>
    <time_frame>from start until end of physiotherapy session, up to 2 days post-operatively</time_frame>
    <description>Level of analgesia during physiotherapy assessed with NRS scale</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Postoperative Pain</condition>
  <arm_group>
    <arm_group_label>sufentanil sublingual tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>sufentanil sublingual 15µg tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sufentanil Sublingual Tablet</intervention_name>
    <description>all patients will receive tablets for sublingual use, containing 15 microgram of sufentanil. The sufentanil tablets come in a cartridge (40 tablets) and are administered with a special patient-controlled device that uses thumb tag recognition.&#xD;
max dose per hour : 3 tablets of 15µg sufentanil</description>
    <arm_group_label>sufentanil sublingual tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients between 40-75 years old&#xD;
&#xD;
          -  Able to give consent&#xD;
&#xD;
          -  Scheduled of elective knee arthroplasty with a fast rehabilitation program&#xD;
&#xD;
          -  Able to understand PCA principle and capable to operate SSTS device&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Outside age range&#xD;
&#xD;
          -  Contra indication for anti-inflammatory drugs&#xD;
&#xD;
          -  Revision total knee arthroplasty&#xD;
&#xD;
          -  history of substance abuse,&#xD;
&#xD;
          -  pregnancy,lactation&#xD;
&#xD;
          -  severe hepatic impairment (INR&gt;1,5 and/or AST/ALT above x3 highest normal value),&#xD;
&#xD;
          -  sleep apnea (documented by sleep laboratory study),&#xD;
&#xD;
          -  severe chronic kidney disease (eGFR&lt;30 mL/min/1.73 m2),&#xD;
&#xD;
          -  severe and very severe COPD (GOLD III and IV)&#xD;
&#xD;
          -  opioid tolerance (use of &gt;15mg oral morphine equivalent per day within the past 3&#xD;
             months),&#xD;
&#xD;
          -  chronic pain conditions necessitating gabapentinoids, steroids or anti-inflammatory&#xD;
             drugs&#xD;
&#xD;
          -  hypersensitivity to sufentanil&#xD;
&#xD;
          -  significant respiratory depression (need for outpatient supplemental oxygen therapy),&#xD;
&#xD;
          -  participation in another clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick Wouters, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Ghent</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Luc Verbacnk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yperman Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Ghent</name>
      <address>
        <city>Ghent</city>
        <state>Oost-Vlaanderen</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>December 3, 2022</last_update_submitted>
  <last_update_submitted_qc>December 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>knee surgery</keyword>
  <keyword>Patient Controlled Analgesia (PCA)</keyword>
  <keyword>Enhansed Recovery After Surgery (ERAS)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sufentanil</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/NCT04432428
org study id: 2019/1741
nct id: NCT04432428
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The sufentanil sublingual tablet system (SSTS) is an innovative patient-controlled analgesia
      (PCA) device for the management of acute moderate to severe postoperative pain in hospital
      settings in adult patients.

      The SSTS is non-invasive and imposes no restrictions on patient mobility, which renders it
      particularly suitable for clinical conditions where early mobilization is a key component of
      successful surgical outcome.

      The present study tests the hypothesis that SSTS is an efficient and safe analgesic technique
      allowing fast track rehabilitation after total knee arthroplasty in a prospective cohort
      design.
Total knee arthroplasty is one of the most common major procedures performed today with a
      significant impact on health care budgets. Fast track rehabilitation programmes are being
      developed to control hospitalization costs associated with this procedure. Interestingly,
      such pathway controlled fast track programs also appear to enhance functional recovery and to
      reduce complications. These beneficial effects are mainly attributed to the practice of rapid
      mobilization and early intensified physiotherapy which can only be achieved with effective
      analgesic techniques.

      Current PCA techniques - predominantly morphine based - are the gold standard for this
      purpose but they involve intravenous access and a programmable computer system requiring
      close supervision. Reported shortcomings are systems failure leading to analgesic gaps, drug
      errors and restrictions in mobility since patients are tethered to IV poles. The SSTS may
      overcome these limitations because the opioid used, sufentanil, has a more predictable time
      of onset, the delivery system does not require programming, and the device does not limit
      patient's mobility. It retains the benefits of potent analgesia as well as patient
      empowerment and is particularly suited to target the analgesic effect precisely to the level
      required in physiotherapeutic sessions.

      The present study will test the hypothesis that SSTS is an efficient and safe analgesic
      technique allowing fast track rehabilitation after total knee arthroplasty in a prospective
      cohort design.

      The study will focus on the efficiency of STSS which is defined as 75% or more of the treated
      patients proves NRS score less than 4 during 48 hours postoperatively, additionally to the
      basic pain treatment (paracetamol and NSAID).

      The STSS will allow the patient tot take a maximum of 3 doses in one hour. Treatment with the
      STSS is continued over a period of 48 hours or if necessary up to 72 hours.

      During this period the patients pain en parameters will be monitored closely.

      The maximum administered total dose of Zalviso will not exceed 1.2mg.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Multicentric interventional prospective cohort study
primary purpose: Treatment
masking: None (Open Label)
measure: Total time NRS<4
time frame: from end of surgery until 48 hours postoperatively
description: cumulative time that patient had NRS<4
measure: length of hospital stay
time frame: from hospital admission until hospital discharge, up to 1 week post-operatively
description: amount of days that patient was admitted to the hosptial
measure: Incidence of the side effect nausea
time frame: from end of surgery until 72 hours postoperatively
description: Incidence of the side effect nausea with a simple scale (none, mild, moderate, severe)
measure: Incidence of the side effect vomiting
time frame: from end of surgery until 72 hours postoperatively
description: Incidence of the side effect vomiting with a simple scale (none, mild, moderate, severe)
measure: Incidence of the side effect itching
time frame: from end of surgery until 72 hours postoperatively
description: Incidence of the side effect itching with a simple scale (none, mild, moderate, severe)
measure: Incidence of the side effect drowsiness
time frame: from end of surgery until 72 hours postoperatively
description: Incidence of the side effect drowsiness with a simple scale (none, mild, moderate, severe)
measure: Incidence of the side effect constipation
time frame: from end of surgery until 72 hours postoperatively
description: Incidence of the side effect constipation with a simple scale (none, mild, moderate, severe)
measure: Oxygen desaturation
time frame: from end of surgery until 72 hours postoperatively
description: Oxygen desaturation
measure: patient satisfaction with Zalviso PCA
time frame: after discontinuation of study medication, up to 72 hrs after start of the study medication
description: patient satisfaction assessed with patient ease of care questionnaire
measure: health care worker satisfaction with the patients pain treatment with Zalviso PCA
time frame: after patients discontinuation of study medication, up to 1 week after stop study medication
description: health care worker satisfaction assessed with nurse/physical therapist ease of care questionnaire
measure: consumption of study medication
time frame: from start administration of study medication until end of administration of study medication, up to a maximum of 72 hrs
description: total amount of study medication that was administered
measure: Level of analgesia during physiotherapy
time frame: from start until end of physiotherapy session, up to 2 days post-operatively
description: Level of analgesia during physiotherapy assessed with NRS scale
arm group label: sufentanil sublingual tablet
arm group type: Experimental
description: sufentanil sublingual 15µg tablets
intervention type: Drug
intervention name: Sufentanil Sublingual Tablet
description: all patients will receive tablets for sublingual use, containing 15 microgram of sufentanil. The sufentanil tablets come in a cartridge (40 tablets) and are administered with a special patient-controlled device that uses thumb tag recognition.
max dose per hour : 3 tablets of 15µg sufentanil
arm group label: sufentanil sublingual tablet
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Patrick Wouters, MD PhD
role: Principal Investigator
affiliation: University Hospital, Ghent
last name: Luc Verbacnk, MD
role: Principal Investigator
affiliation: Yperman Hospital
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Sufentanil
sharing ipd: No