<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/NCT03748602</url>
  </required_header>
  <id_info>
    <org_study_id>NL63986.100.17</org_study_id>
    <nct_id>NCT03748602</nct_id>
  </id_info>
  <brief_title>Surgical Thoracic Outlet Decompression for Neurogenic Thoracic Outlet Syndrome</brief_title>
  <acronym>STOPNTOS</acronym>
  <official_title>Surgical Thoracic Outlet Decompression Versus Conservative Approach for Patients With Neurogenic Thoracic Outlet Syndrome, a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Catharina Ziekenhuis Eindhoven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Catharina Ziekenhuis Eindhoven</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will determine the value of TOD (first rib resection with partial scalenectomy and&#xD;
      neurolysis) on functionality and quality of life for patients with neurogenic thoracic outlet&#xD;
      syndrome. This will be done by randomizing patients into surgery or conservative therapy&#xD;
      (physiotherapy and pain relief).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Neurogenic thoracic outlet syndrome (NTOS) is a condition caused by compression and&#xD;
      irritation of the brachial plexus serving the upper extremity. NTOS most frequently occurs in&#xD;
      relatively young, active and otherwise healthy individuals and can have a tremendous impact&#xD;
      on work, social and personal life. The diagnosis and therapy of NTOS still remains disputed.&#xD;
      This is partly because diagnosis is largely clinical and subjective in nature, with no&#xD;
      definitive (diagnostic) imaging or diagnostic studies available. As a result, disparities in&#xD;
      the definition have produced different opinions regarding diagnostic standards for TOS.&#xD;
      Furthermore, given the controversy surrounding the definition and diagnosis of TOS, conflict&#xD;
      exists regarding the optimal treatment approach for this condition.&#xD;
&#xD;
      Studies in the last years, have shed light on some of the controversies in diagnosing and&#xD;
      treating NTOS. Many patients that benefit from thoracic outlet decompression (TOD) do not fit&#xD;
      the historical diagnostic criteria. Those patients (up to 90%) with disputed NTOS have shown&#xD;
      improvement of symptoms and functionality after TOD surgery.&#xD;
&#xD;
      Recently, several studies have been published about outcome after TOD surgery for NTOS. These&#xD;
      large, multicenter studies show a very low complication rate, ranging from 0-2%, with an&#xD;
      extremely low risk of nerve injury.&#xD;
&#xD;
      These studies however report on heterogenous populations, diagnosed without any&#xD;
      internationally validated diagnostic criteria. They hint beneficial results for TOD in NTOS&#xD;
      patients, however the level of evidence they provide is low. Critics have wondered if the&#xD;
      improvements - reported in these trials - are attributed to surgery, or are merely due to&#xD;
      coincidence, selection bias, conservative treatment or time (rest).&#xD;
&#xD;
      The society of vascular surgery published reporting standards in 2016 to produce consistency&#xD;
      in diagnosis, description of treatment and assessment of results to allow more valuable data&#xD;
      to be reported. The investigators believe that a randomized controlled trial - using the&#xD;
      reporting standards- could demonstrate the actual added value of a TOD (first rib resection&#xD;
      with partial scalenectomy and neurolysis).&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The objective of this study is to determine the value of TOD (first rib resection with&#xD;
      partial scalenectomy and neurolysis) on functionality and quality of life. This will be done&#xD;
      by randomizing patients who already received conservative physiotherapy into surgery or&#xD;
      continued conservative therapy (physiotherapy and pain relief). After 3 months, the patients&#xD;
      with continued maximum conservative therapy will be offered surgery as well if complaints&#xD;
      persist. The effect of TOD will be examined by following the change in functionality and&#xD;
      quality of life compared to conservative physiotherapy. The durability of these effects on&#xD;
      functional assessment and quality of life will also be examined by following patients for 5&#xD;
      years.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      Single center randomized controlled trial&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      All patients diagnosed with NTOS refractory to conservative physiotherapy treatment (based on&#xD;
      criteria produced by the reporting standards) and considered to benefit from TOD in a&#xD;
      multidisciplinary TOS-consensus group are considered candidates for this study.&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      Patients will be randomized into surgery (TOD) versus conservative physiotherapy. The group&#xD;
      randomised for conservative physiotherapy will be offered surgical therapy after 3 months if&#xD;
      complaints persist.&#xD;
&#xD;
      Main study parameters/endpoints:&#xD;
&#xD;
      Primary endpoint is DASH SCORE. This endpoint will be measured with the DASH questionnaire&#xD;
      (Disability of the Arm, Shoulder and Hand) Secondary endpoints will be the score on the CBSQ,&#xD;
      VAS scale and SF 12. These endpoints will be measured with the CBSQ questionnaire&#xD;
      (Cervical-Brachial Symptoms Questionnaire), VAS scale (Visual Analogue Scale for Pain) and SF&#xD;
      12 (Short Form 12 questionnaire)&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness:&#xD;
&#xD;
      All patients are operated with the same technique and by the same operator. There is a delay&#xD;
      of 3 months for half of the subjects (control group), which is relative due to the early&#xD;
      operation (in comparison with the existing waiting list for regular TOD of around 3 months)&#xD;
      of the group that is randomised for TOD. There is no denial of 'optimal medical treatment'&#xD;
      for any of the participating subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 1, 2018</start_date>
  <completion_date type="Anticipated">October 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 1, 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>All patients diagnosed with NTOS refractory to conservative physiotherapy treatment (based on criteria produced by the reporting standards) and considered to benefit from TOD in a multidisciplinary TOS-consensus group are considered candidates for this study.&#xD;
Patients will be randomized into surgery (TOD) versus conservative physiotherapy. The group randomised for conservative physiotherapy will be offered surgical therapy after 3 months if complaints persist.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Disability of the Arm, Shoulder and Hand (DASH) score</measure>
    <time_frame>Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion</time_frame>
    <description>This questionnaire is validated for neurogenic thoracic outlet syndrome and was developed by the American Academy of Traumatology. It includes 30 questions related to symptoms of daily activities and social and psychological functions. Scores range from asymptomatic (0) to totally invalid (100).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Chance in Cervical-Brachial Symptoms (CBSQ) Questionnaire score</measure>
    <time_frame>Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion</time_frame>
    <description>This questionnaire is validated for neurogenic thoracic outlet syndrome and consist out of 12 questions with the answer going from 0 to 10, 2 questions Y/N answers, 1 question with a visual feedback which parts of the neck, shoulder, arm or hand have most symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Visual Analogue Scale (VAS) for Pain</measure>
    <time_frame>Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion</time_frame>
    <description>This scale measures pain going from 0 (none) to 10 (intens) Patients can chose any number between 0 and 10 to accuratly rate their pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Short Form 12 (SF-12) questionnaire score</measure>
    <time_frame>Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion</time_frame>
    <description>This questionnaire measures quality of life. It consist out of 12 questions with answers going from Y/N to 0 to 5</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Neurogenic Thoracic Outlet Syndrome</condition>
  <arm_group>
    <arm_group_label>TOD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thoracic Outlet Decompression (TOD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conservative therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Physiotherapy and pain relief</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Thoracic outlet decompression</intervention_name>
    <description>TOD consists out of first rib resection with partial scalenectomy and neurolysis. If there are also complaints below the pectoral minor tendon insertion, a pectoral minor tenotomy is performed.</description>
    <arm_group_label>TOD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  High suspicion of NTOS with high level of impairment.&#xD;
&#xD;
               -  The decision to refer a patient with NTOS for surgery is placed at the sole&#xD;
                  authority of the TOS multidisciplinary workgroup. Members of this workgroup are 2&#xD;
                  dedicated vascular surgeons, 2 neurologists, 1 orthopedic surgeon, 3&#xD;
                  physiotherapists, 2 radiologists, 3 anesthesiologists.&#xD;
&#xD;
               -  This decision is based on the reporting standards published by Illig et al. in&#xD;
                  2016. If a patient fits the criteria postulated in the reporting standards and if&#xD;
                  there is consensus within the multidisciplinary team, only then patients are&#xD;
                  referred for TOD.&#xD;
&#xD;
          -  Fit for surgery, at the discretion of the treating vascular surgeon and&#xD;
             anesthesiologist.&#xD;
&#xD;
          -  Signed informed consent form.&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  Dutch or English speaking patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unfit for surgery, at the discretion of the treating vascular surgeon and&#xD;
             anesthesiologist.&#xD;
&#xD;
          -  Younger than 18 years of age&#xD;
&#xD;
          -  Patients that do not speak Dutch or English.&#xD;
&#xD;
          -  Patients with a history of TOD&#xD;
&#xD;
          -  Patients that did not receive previous conservative physiotherapy for this condition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joep Teijink, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vascular surgeon - Catharina Ziekenhuis Eindhoven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Catharina Ziekenhuis</name>
      <address>
        <city>Eindhoven</city>
        <state>Noord-Brabant</state>
        <zip>5623 EJ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>July 28, 2022</last_update_submitted>
  <last_update_submitted_qc>July 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Catharina Ziekenhuis Eindhoven</investigator_affiliation>
    <investigator_full_name>Joep Teijink</investigator_full_name>
    <investigator_title>Professor in vascular surgery</investigator_title>
  </responsible_party>
  <keyword>thoracic outlet decompression (TOD)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thoracic Outlet Syndrome</mesh_term>
    <mesh_term>Aortic Dissection</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_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/NCT03748602
org study id: NL63986.100.17
nct id: NCT03748602
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will determine the value of TOD (first rib resection with partial scalenectomy and
      neurolysis) on functionality and quality of life for patients with neurogenic thoracic outlet
      syndrome. This will be done by randomizing patients into surgery or conservative therapy
      (physiotherapy and pain relief).
Background:

      Neurogenic thoracic outlet syndrome (NTOS) is a condition caused by compression and
      irritation of the brachial plexus serving the upper extremity. NTOS most frequently occurs in
      relatively young, active and otherwise healthy individuals and can have a tremendous impact
      on work, social and personal life. The diagnosis and therapy of NTOS still remains disputed.
      This is partly because diagnosis is largely clinical and subjective in nature, with no
      definitive (diagnostic) imaging or diagnostic studies available. As a result, disparities in
      the definition have produced different opinions regarding diagnostic standards for TOS.
      Furthermore, given the controversy surrounding the definition and diagnosis of TOS, conflict
      exists regarding the optimal treatment approach for this condition.

      Studies in the last years, have shed light on some of the controversies in diagnosing and
      treating NTOS. Many patients that benefit from thoracic outlet decompression (TOD) do not fit
      the historical diagnostic criteria. Those patients (up to 90%) with disputed NTOS have shown
      improvement of symptoms and functionality after TOD surgery.

      Recently, several studies have been published about outcome after TOD surgery for NTOS. These
      large, multicenter studies show a very low complication rate, ranging from 0-2%, with an
      extremely low risk of nerve injury.

      These studies however report on heterogenous populations, diagnosed without any
      internationally validated diagnostic criteria. They hint beneficial results for TOD in NTOS
      patients, however the level of evidence they provide is low. Critics have wondered if the
      improvements - reported in these trials - are attributed to surgery, or are merely due to
      coincidence, selection bias, conservative treatment or time (rest).

      The society of vascular surgery published reporting standards in 2016 to produce consistency
      in diagnosis, description of treatment and assessment of results to allow more valuable data
      to be reported. The investigators believe that a randomized controlled trial - using the
      reporting standards- could demonstrate the actual added value of a TOD (first rib resection
      with partial scalenectomy and neurolysis).

      Objective:

      The objective of this study is to determine the value of TOD (first rib resection with
      partial scalenectomy and neurolysis) on functionality and quality of life. This will be done
      by randomizing patients who already received conservative physiotherapy into surgery or
      continued conservative therapy (physiotherapy and pain relief). After 3 months, the patients
      with continued maximum conservative therapy will be offered surgery as well if complaints
      persist. The effect of TOD will be examined by following the change in functionality and
      quality of life compared to conservative physiotherapy. The durability of these effects on
      functional assessment and quality of life will also be examined by following patients for 5
      years.

      Study design:

      Single center randomized controlled trial

      Study population:

      All patients diagnosed with NTOS refractory to conservative physiotherapy treatment (based on
      criteria produced by the reporting standards) and considered to benefit from TOD in a
      multidisciplinary TOS-consensus group are considered candidates for this study.

      Intervention:

      Patients will be randomized into surgery (TOD) versus conservative physiotherapy. The group
      randomised for conservative physiotherapy will be offered surgical therapy after 3 months if
      complaints persist.

      Main study parameters/endpoints:

      Primary endpoint is DASH SCORE. This endpoint will be measured with the DASH questionnaire
      (Disability of the Arm, Shoulder and Hand) Secondary endpoints will be the score on the CBSQ,
      VAS scale and SF 12. These endpoints will be measured with the CBSQ questionnaire
      (Cervical-Brachial Symptoms Questionnaire), VAS scale (Visual Analogue Scale for Pain) and SF
      12 (Short Form 12 questionnaire)

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

      All patients are operated with the same technique and by the same operator. There is a delay
      of 3 months for half of the subjects (control group), which is relative due to the early
      operation (in comparison with the existing waiting list for regular TOD of around 3 months)
      of the group that is randomised for TOD. There is no denial of 'optimal medical treatment'
      for any of the participating subjects.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All patients diagnosed with NTOS refractory to conservative physiotherapy treatment (based on criteria produced by the reporting standards) and considered to benefit from TOD in a multidisciplinary TOS-consensus group are considered candidates for this study.
Patients will be randomized into surgery (TOD) versus conservative physiotherapy. The group randomised for conservative physiotherapy will be offered surgical therapy after 3 months if complaints persist.
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Disability of the Arm, Shoulder and Hand (DASH) score
time frame: Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion
description: This questionnaire is validated for neurogenic thoracic outlet syndrome and was developed by the American Academy of Traumatology. It includes 30 questions related to symptoms of daily activities and social and psychological functions. Scores range from asymptomatic (0) to totally invalid (100).
measure: Chance in Cervical-Brachial Symptoms (CBSQ) Questionnaire score
time frame: Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion
description: This questionnaire is validated for neurogenic thoracic outlet syndrome and consist out of 12 questions with the answer going from 0 to 10, 2 questions Y/N answers, 1 question with a visual feedback which parts of the neck, shoulder, arm or hand have most symptoms.
measure: Change in Visual Analogue Scale (VAS) for Pain
time frame: Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion
description: This scale measures pain going from 0 (none) to 10 (intens) Patients can chose any number between 0 and 10 to accuratly rate their pain.
measure: Change in Short Form 12 (SF-12) questionnaire score
time frame: Change in this outcome will be measured at 0, 3, 6, 12, 24, 36 and 60 months after inclusion
description: This questionnaire measures quality of life. It consist out of 12 questions with answers going from Y/N to 0 to 5
arm group label: TOD
arm group type: Experimental
description: Thoracic Outlet Decompression (TOD)
arm group label: Conservative therapy
arm group type: No Intervention
description: Physiotherapy and pain relief
intervention type: Procedure
intervention name: Thoracic outlet decompression
description: TOD consists out of first rib resection with partial scalenectomy and neurolysis. If there are also complaints below the pectoral minor tendon insertion, a pectoral minor tenotomy is performed.
arm group label: TOD
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Joep Teijink, MD, PhD
role: Principal Investigator
affiliation: Vascular surgeon - Catharina Ziekenhuis Eindhoven
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Catharina Ziekenhuis Eindhoven
investigator full name: Joep Teijink
investigator title: Professor in vascular surgery
mesh term: Thoracic Outlet Syndrome
mesh term: Aortic Dissection
mesh term: Syndrome
sharing ipd: No