<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/NCT03835559</url>
  </required_header>
  <id_info>
    <org_study_id>2018-03-030-001</org_study_id>
    <nct_id>NCT03835559</nct_id>
  </id_info>
  <brief_title>Cyanoacrylate Closure Versus Surgical Stripping for Incompetent Saphenous Veins</brief_title>
  <acronym>CASS</acronym>
  <official_title>Randomized Controlled Trial Comparing the Clinical Outcomes After Cyanoacrylate Closure and Surgical Stripping for Incompetent Saphenous Veins</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kyung Hee University Hospital at Gangdong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kyung Hee University Hospital at Gangdong</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the non-inferior, clinical outcomes after&#xD;
      cyanoacrylate closure comparing the surgical stripping for incompetent saphenous veins.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Varicose veins are highly prevalent. In western countries, an estimated 23% of adults have&#xD;
      varicose veins, and 6% have more advanced chronic venous disease, including skin changes and&#xD;
      healed or active venous ulcers. There are several modalities to treat varicose veins. Open&#xD;
      surgical treatment with ligation and stripping of the saphenous vein, combined with excision&#xD;
      of large varicosities, has been the standard of care for many years. Endovenous thermal&#xD;
      ablation by radiofrequency ablation (RFA) or endovenous laser ablation (EVLA) has been shown&#xD;
      to be a safe and effective alternatives with high long-term target vein closure rates.&#xD;
      Although both techniques have gained broad acceptance in many countries, one major&#xD;
      disadvantage of these techniques is the requirement for use of tumescent anesthesia to avoid&#xD;
      the thermal injury of the surrounding structures. Cyanoacrylate closure for varicose veins&#xD;
      has recently been introduced for treatment of the incompetent saphenous vein.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 10, 2019</start_date>
  <completion_date type="Anticipated">February 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2020</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>Multicenter, prospective randomized controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Closure rate of the target vein/ Absence of refluxing vein</measure>
    <time_frame>3 months</time_frame>
    <description>The primary endpoint of the study is to evaluate the complete closure of the target vein where complete closure is defined as Doppler ultrasound showing vein closure along entire treated vein segment with no discrete segments of patency exceeding 5cm after cyanoacrylate closure and absence of refluxing vein or residual vein after surgical stripping as read by a qualified site technologist or investigator.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Perioperative pain with visual analog scale</measure>
    <time_frame>3 days</time_frame>
    <description>The subject will be asked to rate pain on a 0-10 numeric rating scale. (minimum-0 (best), maximum-10 (worst))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ecchymosis</measure>
    <time_frame>3 days</time_frame>
    <description>The investigator will score the subjects ipsilateral leg of the occurrence of ecchymosis along treated segment, rated on a 0- to 5-point graded scale (0, none; 1, involving &lt;25% of the treatment area; 2, 25%-50%; 3, 50%-75%; 4, 75%-100%; 5, extension above or below the treatment segment)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Venous Clinical Severity Score</measure>
    <time_frame>1, 3, 6, 12 and 24 months after treatment</time_frame>
    <description>Severity score on a 0-30 numeric rating scale ((minimum-0 (best), maximum-30 (worst))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptability of Quality of life score</measure>
    <time_frame>1, 3, 6, 12 and 24 months after treatment</time_frame>
    <description>The quality of life scores are measured by the Aberdeen Varicose Vein Questionnaire (AVVQ) and EuroQOL five dimensions questionnaire (EQ-5D).&#xD;
The AVVQs are scored using a questionnaire. The total score for the 13 questions ranges from 0 to 100 points, with 0 points indicating the best possible quality of life. The EuroQOL is an instrument which evaluates the generic quality of life. The EuroQOL descriptive system is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction of the patients: satisfaction rate</measure>
    <time_frame>1, 3, 6, 12 and 24 months after treatment</time_frame>
    <description>The subject will be asked to the satisfaction rate by five response categories (strongly agree, agree, uncertain, disagree, strongly disagree) after asking as following: I'm very satisfied with the medical care I receive.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">146</enrollment>
  <condition>Occlusions Vein</condition>
  <condition>Chronic Venous Insufficiency</condition>
  <arm_group>
    <arm_group_label>Cyanoacrylate closure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After successful access of target vein and insertion of guidewire under any type of anesthesia, the procedure of cyanoacrylate closure for treatment of incompetent Saphenous Veins is performed. A 5 French introducer and catheter is advanced and positioned 5.0 cm caudal to the junction with proximal saphenous vein compression by the ultrasound probe, two injections of approximately 0.10 mL glue are given 1 cm apart, followed by a 3min period of compression, and then repeat injections and 30sec ultrasound probe and hand compression sequences until the entire length of the target vein is treated. The catheter is removed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surgical stripping</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>For treatment of incompetent Saphenous Veins, surgical stripping is performed with a proper incision in the groin, with division and ligation of the saphenous vein and division of all tributaries under all types of anesthesia (general, spinal, regional block, or local anesthesia). The saphenous vein is then removed using a stripper. Compression stocking is apply.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cyanoacrylate closure</intervention_name>
    <description>After successful access of target vein and insertion of guidewire under any type of anesthesia, the procedure of cyanoacrylate closure is performed. A 5 French introducer and catheter is advanced and positioned 5.0 cm caudal to the junction with proximal saphenous vein compression by the ultrasound probe, two injections of approximately 0.10 mL glue are given 1 cm apart, followed by a 3min period of compression, and then repeat injections and 30sec ultrasound probe and hand compression sequences until the entire length of the target vein is treated. The catheter is removed.</description>
    <arm_group_label>Cyanoacrylate closure</arm_group_label>
    <arm_group_label>Surgical stripping</arm_group_label>
    <other_name>Cyanoacrylate closure for incompetent Saphenous vein</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgical stripping</intervention_name>
    <description>All types of anesthesia (general, spinal, regional block, or local anesthesia) can be used. The surgical stripping is performed with a proper incision in the groin, with division and ligation of the saphenous vein and division of all tributaries. The saphenous vein is then removed using a stripper.</description>
    <arm_group_label>Cyanoacrylate closure</arm_group_label>
    <arm_group_label>Surgical stripping</arm_group_label>
    <other_name>Surgical stripping for incompetent Saphenous vein</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 and 80 years of age at the time of enrollment&#xD;
&#xD;
          -  Reflux in great saphenous vein greater than 0.5 seconds after distal compression and&#xD;
             release or Valsalva's maneuver in the standing or reverse Trendelenburg position&#xD;
&#xD;
          -  Diameter of saphenous vein between 2mm to 20mm (with standing position)&#xD;
&#xD;
          -  One or more of the following symptoms related to the incompetent saphenous vein:&#xD;
             aching, throbbing, heaviness, fatigue, pruritus, night cramps, restlessness,&#xD;
             generalized pain or discomfort, swelling&#xD;
&#xD;
          -  Clinical, Etiologic, Anatomic, and Pathophysiologic classification of C2 through C5&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment in targeted vein segment&#xD;
&#xD;
          -  Tortuous vein in which the delivery catheter cannot be inserted&#xD;
&#xD;
          -  Aneurysm of target vein segment &gt;20 mm&#xD;
&#xD;
          -  Daily use of narcotic or nonsteroidal anti-inflammatory pain medications to control&#xD;
             pain associated with greater saphenous vein reflux&#xD;
&#xD;
          -  Known hypercoagulable disorder&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  Regular use of systemic anticoagulation&#xD;
&#xD;
          -  Current use of systemic anticoagulant&#xD;
&#xD;
          -  Previous deep vein thrombosis/pulmonary embolism or active acute superficial&#xD;
             thrombophlebitis&#xD;
&#xD;
          -  Unable to comply with the schedule and protocol evaluations&#xD;
&#xD;
          -  Unable to ambulate&#xD;
&#xD;
          -  Currently pregnant or breast feeding&#xD;
&#xD;
          -  Known sensitivity to cyanoacrylate adhesives&#xD;
&#xD;
          -  Symptomatic peripheral arterial disease with ankle-brachial index &lt;0.9&#xD;
&#xD;
          -  Participation in another clinical study that has not reached primary endpoint within&#xD;
             30 days prior to enrollment&#xD;
&#xD;
          -  Any condition which in the opinion of the investigator could compromise subject safety&#xD;
             or adherence to the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jin Hyun Joh, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kyung Hee University Hospital at Gangdong, Seoul, Korea</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Hyun Joh, MD, PhD</last_name>
    <phone>+82-2-440-6261</phone>
    <email>vascularjoh@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>In-Mok Jung</name>
      <address>
        <city>Seoul</city>
        <state>Non US/Canada</state>
        <zip>05278</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin H Joh</last_name>
      <email>vascularjoh@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jin Hyun Joh</name>
      <address>
        <city>Seoul</city>
        <state>Non US/Canada</state>
        <zip>05278</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin H Joh</last_name>
      <email>vascularjoh@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <results_reference>
    <citation>Kaplan RM, Criqui MH, Denenberg JO, Bergan J, Fronek A. Quality of life in patients with chronic venous disease: San Diego population study. J Vasc Surg. 2003 May;37(5):1047-53. doi: 10.1067/mva.2003.168.</citation>
    <PMID>12756353</PMID>
  </results_reference>
  <results_reference>
    <citation>van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009 Jan;49(1):230-9. doi: 10.1016/j.jvs.2008.06.030. Epub 2008 Aug 9.</citation>
    <PMID>18692348</PMID>
  </results_reference>
  <results_reference>
    <citation>Morrison N, Gibson K, McEnroe S, Goldman M, King T, Weiss R, Cher D, Jones A. Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous veins (VeClose). J Vasc Surg. 2015 Apr;61(4):985-94. doi: 10.1016/j.jvs.2014.11.071. Epub 2015 Jan 31.</citation>
    <PMID>25650040</PMID>
  </results_reference>
  <results_reference>
    <citation>Kolluri R, Gibson K, Cher D, Madsen M, Weiss R, Morrison N. Roll-in phase analysis of clinical study of cyanoacrylate closure for incompetent great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2016 Oct;4(4):407-15. doi: 10.1016/j.jvsv.2016.06.017. Epub 2016 Aug 8.</citation>
    <PMID>27638993</PMID>
  </results_reference>
  <results_reference>
    <citation>Chan YC, Law Y, Cheung GC, Ting AC, Cheng SW. Cyanoacrylate glue used to treat great saphenous reflux: Measures of outcome. Phlebology. 2017 Mar;32(2):99-106. doi: 10.1177/0268355516638200. Epub 2016 Jul 9.</citation>
    <PMID>27052039</PMID>
  </results_reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>April 13, 2019</last_update_submitted>
  <last_update_submitted_qc>April 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kyung Hee University Hospital at Gangdong</investigator_affiliation>
    <investigator_full_name>Jin Hyun Joh</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>varicose vein</keyword>
  <keyword>stripping</keyword>
  <keyword>endovenous</keyword>
  <keyword>ablation</keyword>
  <keyword>Occlusion</keyword>
  <keyword>quality of life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Venous Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Study protocol</ipd_description>
  </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/NCT03835559
org study id: 2018-03-030-001
nct id: NCT03835559
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the non-inferior, clinical outcomes after
      cyanoacrylate closure comparing the surgical stripping for incompetent saphenous veins.
Varicose veins are highly prevalent. In western countries, an estimated 23% of adults have
      varicose veins, and 6% have more advanced chronic venous disease, including skin changes and
      healed or active venous ulcers. There are several modalities to treat varicose veins. Open
      surgical treatment with ligation and stripping of the saphenous vein, combined with excision
      of large varicosities, has been the standard of care for many years. Endovenous thermal
      ablation by radiofrequency ablation (RFA) or endovenous laser ablation (EVLA) has been shown
      to be a safe and effective alternatives with high long-term target vein closure rates.
      Although both techniques have gained broad acceptance in many countries, one major
      disadvantage of these techniques is the requirement for use of tumescent anesthesia to avoid
      the thermal injury of the surrounding structures. Cyanoacrylate closure for varicose veins
      has recently been introduced for treatment of the incompetent saphenous vein.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicenter, prospective randomized controlled trial
primary purpose: Treatment
masking: None (Open Label)
measure: Closure rate of the target vein/ Absence of refluxing vein
time frame: 3 months
description: The primary endpoint of the study is to evaluate the complete closure of the target vein where complete closure is defined as Doppler ultrasound showing vein closure along entire treated vein segment with no discrete segments of patency exceeding 5cm after cyanoacrylate closure and absence of refluxing vein or residual vein after surgical stripping as read by a qualified site technologist or investigator.
measure: Perioperative pain with visual analog scale
time frame: 3 days
description: The subject will be asked to rate pain on a 0-10 numeric rating scale. (minimum-0 (best), maximum-10 (worst))
measure: Ecchymosis
time frame: 3 days
description: The investigator will score the subjects ipsilateral leg of the occurrence of ecchymosis along treated segment, rated on a 0- to 5-point graded scale (0, none; 1, involving <25% of the treatment area; 2, 25%-50%; 3, 50%-75%; 4, 75%-100%; 5, extension above or below the treatment segment)
measure: Venous Clinical Severity Score
time frame: 1, 3, 6, 12 and 24 months after treatment
description: Severity score on a 0-30 numeric rating scale ((minimum-0 (best), maximum-30 (worst))
measure: Acceptability of Quality of life score
time frame: 1, 3, 6, 12 and 24 months after treatment
description: The quality of life scores are measured by the Aberdeen Varicose Vein Questionnaire (AVVQ) and EuroQOL five dimensions questionnaire (EQ-5D).
The AVVQs are scored using a questionnaire. The total score for the 13 questions ranges from 0 to 100 points, with 0 points indicating the best possible quality of life. The EuroQOL is an instrument which evaluates the generic quality of life. The EuroQOL descriptive system is a preference-based measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).
measure: Satisfaction of the patients: satisfaction rate
time frame: 1, 3, 6, 12 and 24 months after treatment
description: The subject will be asked to the satisfaction rate by five response categories (strongly agree, agree, uncertain, disagree, strongly disagree) after asking as following: I'm very satisfied with the medical care I receive.
arm group label: Cyanoacrylate closure
arm group type: Active Comparator
description: After successful access of target vein and insertion of guidewire under any type of anesthesia, the procedure of cyanoacrylate closure for treatment of incompetent Saphenous Veins is performed. A 5 French introducer and catheter is advanced and positioned 5.0 cm caudal to the junction with proximal saphenous vein compression by the ultrasound probe, two injections of approximately 0.10 mL glue are given 1 cm apart, followed by a 3min period of compression, and then repeat injections and 30sec ultrasound probe and hand compression sequences until the entire length of the target vein is treated. The catheter is removed.
arm group label: Surgical stripping
arm group type: Active Comparator
description: For treatment of incompetent Saphenous Veins, surgical stripping is performed with a proper incision in the groin, with division and ligation of the saphenous vein and division of all tributaries under all types of anesthesia (general, spinal, regional block, or local anesthesia). The saphenous vein is then removed using a stripper. Compression stocking is apply.
intervention type: Procedure
intervention name: Cyanoacrylate closure
description: After successful access of target vein and insertion of guidewire under any type of anesthesia, the procedure of cyanoacrylate closure is performed. A 5 French introducer and catheter is advanced and positioned 5.0 cm caudal to the junction with proximal saphenous vein compression by the ultrasound probe, two injections of approximately 0.10 mL glue are given 1 cm apart, followed by a 3min period of compression, and then repeat injections and 30sec ultrasound probe and hand compression sequences until the entire length of the target vein is treated. The catheter is removed.
arm group label: Cyanoacrylate closure
arm group label: Surgical stripping
other name: Cyanoacrylate closure for incompetent Saphenous vein
intervention type: Procedure
intervention name: Surgical stripping
description: All types of anesthesia (general, spinal, regional block, or local anesthesia) can be used. The surgical stripping is performed with a proper incision in the groin, with division and ligation of the saphenous vein and division of all tributaries. The saphenous vein is then removed using a stripper.
arm group label: Cyanoacrylate closure
arm group label: Surgical stripping
other name: Surgical stripping for incompetent Saphenous vein
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jin Hyun Joh, MD, PhD
role: Principal Investigator
affiliation: Kyung Hee University Hospital at Gangdong, Seoul, Korea
last name: Jin Hyun Joh, MD, PhD
phone: +82-2-440-6261
email: vascularjoh@gmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
citation: Kaplan RM, Criqui MH, Denenberg JO, Bergan J, Fronek A. Quality of life in patients with chronic venous disease: San Diego population study. J Vasc Surg. 2003 May;37(5):1047-53. doi: 10.1067/mva.2003.168.
PMID: 12756353
citation: van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009 Jan;49(1):230-9. doi: 10.1016/j.jvs.2008.06.030. Epub 2008 Aug 9.
PMID: 18692348
citation: Morrison N, Gibson K, McEnroe S, Goldman M, King T, Weiss R, Cher D, Jones A. Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous veins (VeClose). J Vasc Surg. 2015 Apr;61(4):985-94. doi: 10.1016/j.jvs.2014.11.071. Epub 2015 Jan 31.
PMID: 25650040
citation: Kolluri R, Gibson K, Cher D, Madsen M, Weiss R, Morrison N. Roll-in phase analysis of clinical study of cyanoacrylate closure for incompetent great saphenous veins. J Vasc Surg Venous Lymphat Disord. 2016 Oct;4(4):407-15. doi: 10.1016/j.jvsv.2016.06.017. Epub 2016 Aug 8.
PMID: 27638993
citation: Chan YC, Law Y, Cheung GC, Ting AC, Cheng SW. Cyanoacrylate glue used to treat great saphenous reflux: Measures of outcome. Phlebology. 2017 Mar;32(2):99-106. doi: 10.1177/0268355516638200. Epub 2016 Jul 9.
PMID: 27052039
responsible party type: Principal Investigator
investigator affiliation: Kyung Hee University Hospital at Gangdong
investigator full name: Jin Hyun Joh
investigator title: Associate professor
mesh term: Venous Insufficiency
sharing ipd: Undecided
ipd description: Study protocol