<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/NCT04452240</url>
  </required_header>
  <id_info>
    <org_study_id>EVF01</org_study_id>
    <nct_id>NCT04452240</nct_id>
  </id_info>
  <brief_title>Safety, Efficacy and Cost Analysis of the Conformable Thoracic Stent Graft With ACTIVE CONTROL</brief_title>
  <acronym>CONFORTA</acronym>
  <official_title>Clinical Study to Evaluate the Safety, Efficacy and Cost Analysis of the GORE® TAG® Conformable Thoracic Stent Graft With ACTIVE CONTROL System FOR Patients With Descending Thoracic Aortic Pathologies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Endovascular Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>W.L.Gore &amp; Associates</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bocconi University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Endovascular Foundation</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>
      Study Design This is a prospective, multicenter, non-randomized clinical study in patients&#xD;
      presenting thoracic aortic pathologies.&#xD;
&#xD;
      Following a baseline assessment, the implantation procedure will be performed according to&#xD;
      the Instructions for Use and local routine practice. A follow-up visit will be performed 30&#xD;
      days, 6, 12,24 and 36 months after the implantation procedure.&#xD;
&#xD;
      The investigator will perform assessments of the implantation procedure and device system and&#xD;
      document adverse events (AE) and device deficiencies. Resources utilization and unit costs&#xD;
      will be collected at index procedure and during follow-up. HRQoL is going to be investigated&#xD;
      in this prospective study using the generic questionnaire EQ5D 5 levels, comparing pre- and&#xD;
      postoperative scores.&#xD;
&#xD;
      Study Objective The objective of the study is to evaluate the safety, performance and&#xD;
      resource utilization associated with the use of GORE® TAG® Conformable Thoracic Stent Graft&#xD;
      with ACTIVE CONTROL systems in humans having thoracic aortic pathologies. Safety will be&#xD;
      evaluated considering mortality and morbidity variables (mainly focused on device related&#xD;
      complications). Efficacy will be evaluated according to the variables related to the&#xD;
      technical and clinical successes. In addition, resource utilization and associated costs will&#xD;
      be collected prospectively with the objective to analyze differences in resource utilization&#xD;
      between outcome groups, landing zone groups, disease severity groups, adverse event groups&#xD;
      and case-mix groups. We will calculate the average marginal costs increase for complications&#xD;
      when they occurred during TEVAR or surgical revascularization (e.g., paralysis, stroke, nerve&#xD;
      injury, lymph damages, myocardial infarction, major bleeding event, respiratory&#xD;
      complication). Resource utilization analysis is not going to be limited to the index&#xD;
      procedure but will continue during follow-up.&#xD;
&#xD;
      Subject Population: Elective and Urgent Thoracic aorta pathologies such as aneurysms,&#xD;
      pseudoaneurysms, dissections, blunt thoracic aorta injury, penetrating ulcers and intramural&#xD;
      hematoma.&#xD;
&#xD;
      Planned number of patients: A total of 200 patients. Approx. 20 study centers in 2 European&#xD;
      countries (15 in Italy and 5 in Spain) . A subgroup of 8centers will be selected for the&#xD;
      micro-costing analysis (7 in Italy and one in Barcelona) Expected Time to Complete&#xD;
      Enrollment: end of 2021 (18 months).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Brief Summary: Study Design This is a prospective, multicenter, non-randomized clinical study&#xD;
      in patients presenting thoracic aortic pathologies.&#xD;
&#xD;
      Following a baseline assessment, the implantation procedure will be performed according to&#xD;
      the Instructions for Use and local routine practice. A follow-up visit will be performed 30&#xD;
      days, 6, 12,24 and 36 months after the implantation procedure.&#xD;
&#xD;
      The investigator will perform assessments of the implantation procedure and device system and&#xD;
      document adverse events (AE) and device deficiencies. Resources utilization and unit costs&#xD;
      will be collected at index procedure and during follow-up. HRQoL is going to be investigated&#xD;
      in this prospective study using the generic questionnaire EQ5D 5 levels, comparing pre- and&#xD;
      postoperative scores.&#xD;
&#xD;
      Study Objective The objective of the study is to evaluate the safety, performance and&#xD;
      resource utilization associated with the use of GORE® TAG® Conformable Thoracic Stent Graft&#xD;
      with ACTIVE CONTROL systems in humans having thoracic aortic pathologies. Safety will be&#xD;
      evaluated considering mortality and morbidity variables (mainly focused on device related&#xD;
      complications). Efficacy will be evaluated according to the variables related to the&#xD;
      technical and clinical successes. In addition, resource utilization and associated costs will&#xD;
      be collected prospectively with the objective to analyze differences in resource utilization&#xD;
      between outcome groups, landing zone groups, disease severity groups, adverse event groups&#xD;
      and case-mix groups. The investigators will calculate the average marginal costs increase for&#xD;
      complications when they occurred during TEVAR or surgical revascularization (e.g., paralysis,&#xD;
      stroke, nerve injury, lymph damages, myocardial infarction, major bleeding event, respiratory&#xD;
      complication). Resource utilization analysis is not going to be limited to the index&#xD;
      procedure but will continue during follow-up.&#xD;
&#xD;
      Subject Population: Elective and Urgent Thoracic aorta pathologies such as aneurysms,&#xD;
      pseudoaneurysms, dissections, blunt thoracic aorta injury, penetrating ulcers and intramural&#xD;
      hematoma.&#xD;
&#xD;
      Planned number of patients: A total of 200 patients. Approx. 20 study centers in 2 European&#xD;
      countries (15 in Italy and 5 in Spain) . A subgroup of 8centers will be selected for the&#xD;
      micro-costing analysis (7 in Italy and one in Barcelona) Expected Time to Complete&#xD;
      Enrollment: end of 2021 (18 months).&#xD;
&#xD;
      Detailed Description: 1. Introduction 1.1. Disease1 A thoracic aortic aneurysm (TAA) and&#xD;
      pseudoaneurysm Type B aortic dissection (TBAD) Intramural hematoma (IMH). IMH may be a&#xD;
      precursor to both classic AD and penetrating aortic ulcer (PAU).&#xD;
&#xD;
      Blunt thoracic aortic injury (BTAI) 1.3. Study Device Description GORE® TAG® Conformable&#xD;
      Thoracic Stent Graft with ACTIVE CONTROL System is a device designed for the endovascular&#xD;
      repair of TAAs, BTAIs, and TBADs of the thoracic aorta. The controlled deployment is designed&#xD;
      to optimize accuracy, angulation, and apposition. Its conformability with enhanced control&#xD;
      allows for optimized wall apposition even in the complex aortic anatomy 2. Study Objectives&#xD;
      2.1. Primary Objective(s) The primary objective of CONFORTA Clinical study is to evaluate the&#xD;
      safety, efficacy of the GORE® TAG® Conformable Thoracic Stent Graft for the treatment of&#xD;
      patients with Thoracic Aortic pathologies.&#xD;
&#xD;
      2.2. Secondary Objective(s) 2.2.1. Health Economic Data healthcare organizations must&#xD;
      identify and address waste in healthcare and reduce the total cost of care. The secondary&#xD;
      objective of this trial is focusing on patient-based costing (PBC).&#xD;
&#xD;
      To provide patient care cost a micro-costing analysis (a cost estimation method that involves&#xD;
      the direct enumeration and costing out of every input consumed in the treatment of a&#xD;
      particular patient) will be conducted together with an assessment of patient QoL alongside&#xD;
      the study data collection.&#xD;
&#xD;
      2.2.2. Quality of Life data This health status information is collected before and after a&#xD;
      procedure and provides an indication of the outcomes or quality of care delivered to the&#xD;
      patient. Among different PROMs, the preference-based measure, such as the EQ-5D and Health&#xD;
      Utilities Index, describes patients' responses to questions not to provide a score 3. Study&#xD;
      Design 3.1. Description of Study Design This study is a prospective, multicenter,&#xD;
      non-randomized single-arm study to evaluate the safety and efficacy of the GORE TAG&#xD;
      Conformable Thoracic Stent Graft with ACTIVE CONTROL system for the treatment of patients&#xD;
      descending Thoracic Aortic pathologies.&#xD;
&#xD;
      Centers from Italy and Spain will be invited to participate to the study. A minimum of 20&#xD;
      Clinical Sites (15 in Italy and 5 in Spain) will participate in this study with two hundred&#xD;
      patients estimated in this study.&#xD;
&#xD;
      Patients may be enrolled into the study provided all inclusion and no exclusion criteria are&#xD;
      met as specified in Section 4. Subjects will be evaluated through hospital discharge and&#xD;
      return for follow-up visits at 30 days, 6, 12, 24 and 36 months after the implantation&#xD;
      procedure. The cost analysis is limited to the 7 Italian centers located in Region Lombardia&#xD;
      and one in Barcelona (Hospital Clinic of Barcelona).&#xD;
&#xD;
      3.2. Study Endpoints 3.2.1. Primary Endpoints&#xD;
&#xD;
        -  Freedom from descending thoracic aorta-related mortality&#xD;
&#xD;
        -  Delivery /deployment success of the study device systems&#xD;
&#xD;
      This evaluation will include the following:&#xD;
&#xD;
        -  evaluation of the delivery system&#xD;
&#xD;
        -  overall rate of vascular access complications (≤30 days)&#xD;
&#xD;
        -  rate of access failures&#xD;
&#xD;
        -  rate of deployment system difficulties&#xD;
&#xD;
        -  Rate of angulation tool usage&#xD;
&#xD;
        -  Rate of arterial pressure reduction maneuver 3.2.2. Secondary study endpoints&#xD;
&#xD;
        -  Micro-costing analysis&#xD;
&#xD;
        -  Change in QoL from baseline 4. Study Population 4.1. Description of Population Patients&#xD;
           with Elective and Urgent Thoracic aorta pathologies such as TAAs, pseudoaneurysms,&#xD;
           TBADs, BTAIs, PAUs and IMHs, are eligible for screening for participation in the study.&#xD;
&#xD;
      Only patients who meet all of the Inclusion Criteria and none of the Exclusion Criteria will&#xD;
      be enrolled.&#xD;
&#xD;
      4.2. Inclusion Criteria Described in another section 4.3. Exclusion criteria: Described in&#xD;
      another section 5. Study Procedures/Evaluations Sites are required to use a CTA scan or MRI&#xD;
      alternatively ultrasound to assess the inserted device, permeability and integrity. Each Site&#xD;
      will be responsible for maintaining and calibrating the equipment used.&#xD;
&#xD;
      5.1. Schedule of Events 5.2. Informed Consent Process All patients must provide informed&#xD;
      consent prior to any study related procedures being performed. The case history (i.e., source&#xD;
      documents/Subject chart) for each Subject shall document that such informed consent was&#xD;
      obtained. The Ethical Committee (EC) approved consent form will be signed and personally&#xD;
      dated by the Subject and the person who conducted the informed consent discussion. The&#xD;
      original signed informed consent form will be retained in the Subject records. A copy of the&#xD;
      informed consent document will be given to the Subject for their records.&#xD;
&#xD;
      5.3. Baseline Prior to entry into this study, all patients will be screened for eligibility.&#xD;
      Screening assessments may be performed over several days and to the day of implant. The&#xD;
      following examinations will be performed and respective data recorded 5.4. Procedure The&#xD;
      endovascular placement of the stent-graft will be performed as described in the Instructions&#xD;
      for Use (contains details about techniques and methods for device deployment and&#xD;
      implantation) and according to local practice at the site.&#xD;
&#xD;
      5.5. Hospital discharge&#xD;
&#xD;
      The patients will be discharged from the clinic at the discretion of the investigator after&#xD;
      performance of the following assessments:&#xD;
&#xD;
        -  Physical examination&#xD;
&#xD;
        -  Documentation of duration of intensive care unit (ICU) admission&#xD;
&#xD;
        -  The investigator will document all AE and relevant concomitant medication/procedures&#xD;
&#xD;
        -  Resource consumption questionnaire 5.6. Follow-Up Subjects will be evaluated through&#xD;
           hospital discharge and return for follow-up visits at 30 days, 6, 12, 24 and 36 months&#xD;
           after the implantation procedure.&#xD;
&#xD;
      5.7. Subject Withdrawal from the Study A Subject may withdraw from the study at any time and&#xD;
      should notify the Investigator in this event. The Investigator may also withdraw the Subject&#xD;
      from the study at any time based on his / her medical judgment.&#xD;
&#xD;
      5.8. Subject Lost to Follow-Up A Subject will be considered lost to follow-up and withdrawn&#xD;
      from the study once they have missed two consecutive follow-up visits and three documented&#xD;
      attempts have been made by the Investigator or designee to contact the Subject or next of&#xD;
      kin.&#xD;
&#xD;
      5.9. Subject Study Completion A Subject has completed the study when final completion of all&#xD;
      follow up visits are done. Any Subject that does not complete these requirements due to&#xD;
      voluntary withdrawal, physician withdrawal, death, or any other reason will be considered a&#xD;
      withdrawal..&#xD;
&#xD;
      6. Study Administration 6.1. Monitoring Site monitoring for this study will be provided by&#xD;
      CRO Leon Research S.L.&#xD;
&#xD;
      6.2. Core Lab Core Lab services for this study will be provided by external independent&#xD;
      observers provided by Endovascular Foundation. Core Lab assessment could be for all imaging&#xD;
      morphometries related to 100% of the included cases or for a random sample, depending on the&#xD;
      promoter final decision.&#xD;
&#xD;
      6.3. Protocol Deviations A Protocol deviation is defined as any change, divergence, or&#xD;
      departure from the study design or procedures of a research protocol. The Investigator is&#xD;
      responsible for promptly recording and reporting Protocol Deviations to the local Ethical&#xD;
      Committee.&#xD;
&#xD;
      6.4. Protocol Amendments The Investigator will obtain EC approval on all amendments in a&#xD;
      timely manner.&#xD;
&#xD;
      6.5. Access to Source Data/Documents Source data are defined as all information necessary for&#xD;
      the reconstruction and evaluation of the Clinical Investigation.&#xD;
&#xD;
      The Investigator will keep all study records, source data available for inspection by the&#xD;
      CRO's monitors, EC and regulatory authorities.&#xD;
&#xD;
      6.6. Study Records Retention The Investigator will maintain complete, accurate and current&#xD;
      study records as required by applicable regulatory requirements. Records will be maintained&#xD;
      during the study and for a minimum of 5 years.&#xD;
&#xD;
      6.7. Publication Plan It is the intent of the Promoter that the multicenter results of this&#xD;
      study will be submitted for publication (in a peer reviewed journal). A publications&#xD;
      committee will be established to review the multicenter results and develop publications at&#xD;
      the completion of the study.&#xD;
&#xD;
      7. Data Collection and Submission 7.1. Data Collection Methods The electronic data capture&#xD;
      system (EDC system) for this study will be provided by Xolomon Tree S.L.&#xD;
&#xD;
      7.2. Data Clarification and Correction by electronic queries 7.3. Case Report Form (CRF)&#xD;
      Completion Schedule: 7.3.1. Baseline Demographics, clinical status and anatomical&#xD;
      morphometrics should be provide to the data base manager prior to the inclusion and prior to&#xD;
      the procedure 7.3.2. Procedural data should be provided with an acceptable window of 1 week&#xD;
      after the index procedure 7.3.3. Follow-up data, Clinical and imaging information, at 1, 6,&#xD;
      12 and 24 months will have an acceptable window of 14 days for 1 month and 30 days for the&#xD;
      rest.&#xD;
&#xD;
      7.3.4. Resource utilization information will be included in the CRF in combination with&#xD;
      dedicated OR CRF 8. Risk Assessment The warnings and precautions when using the&#xD;
      investigational device are described in detail in the Instructions for Use.&#xD;
&#xD;
      8.1. Risk-to-Benefit Rationale Risks are inherent to the endovascular repair of the thoracic&#xD;
      aorta. Benefits are related to the repair of the pathological entity. Risk / benefit should&#xD;
      be assessed by the physician in charge, explained to the patient and accepted, by signed&#xD;
      informed consent, by the patient or other legal representative.&#xD;
&#xD;
      9. Adverse Events (AE) and Safety Monitoring 9.1. Anticipated AE Anticipated AE are&#xD;
      complications that are known to be associated with thoracic aortic pathologies which are&#xD;
      planned to undergo TEVAR with a stent-graft. See Section 8, Risk Assessment.&#xD;
&#xD;
      9.2. Unanticipated Serious Adverse Device Effects (USADE) Serious adverse device effect which&#xD;
      by its nature, incidence, severity or outcome has not been identified in the current version&#xD;
      of the risk analysis report. NOTE: Anticipated: an effect which by its nature, incidence,&#xD;
      severity or outcome has been previously identified in the risk analysis report.&#xD;
&#xD;
      10. Statistical Analysis 10.1. Study Hypotheses The used thoracic endograft device, C-TAG&#xD;
      active control, has high safety and effectiveness, in terms of very low rates of&#xD;
      device-related complications, high accuracy on deployment and solution of the underlying&#xD;
      pathology.&#xD;
&#xD;
      10.2. Sample Size Assumptions A cohort of a minimum of 200 cases is enough to prove our&#xD;
      hypothesis according to previous clinical reports with similar devices. Technical&#xD;
      improvements will be easily assessed by experienced operators with large expertise with&#xD;
      similar devices.&#xD;
&#xD;
      10.3. Sample Size Determination That is a case series study. 200 cases are comparable with&#xD;
      similar series already published in the literature with other similar devices for similar&#xD;
      indications.&#xD;
&#xD;
      10.4. Data Analysis 10.4.1. Timing of Analyses An interim clinical analysis can be considered&#xD;
      when the sample will reach 50% of the final goal.&#xD;
&#xD;
      10.4.2. Analysis Populations Consecutive patients with thoracic aorta pathology according to&#xD;
      the inclusion and exclusion criteria previously described. The investigators will replace&#xD;
      missing or removed cases in order to have the goal population included.&#xD;
&#xD;
      10.4.3. Statistical Analysis of Primary Endpoint(s) Quantitative parameters will be described&#xD;
      using the following summary descriptive statistics: number of non-missing values, mean,&#xD;
      standard deviation, median, first and third quartiles, and minimum and maximum values.&#xD;
&#xD;
      10.4.4. Statistical Analysis of Secondary Endpoint(s) The rate of MAEs will be assessed at 1&#xD;
      year and following time points and will be derived as: all-cause death, bowel ischemia,&#xD;
      myocardial infarction, paraplegia, renal failure, respiratory failure, and secondary&#xD;
      endovascular procedure as defined in section 9, stroke, and procedural blood loss ≥1,000mL.&#xD;
&#xD;
      11. Cost and QoL analysis 11.1. Micro-costing analysis Micro-costing analysis will be&#xD;
      conducted to assess cost associated to each patient enrolled in the trial from the beginning&#xD;
      of the hospitalization to the study follow-up in the perspective of the provider that need to&#xD;
      consider budget constraints.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>36 Years</target_duration>
  <primary_outcome>
    <measure>• Freedom from descending thoracic aorta-related mortality</measure>
    <time_frame>0-3 years</time_frame>
    <description>Mortality rate related to the descending thoracic aorta condition or its endovascular repair or procedure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>• Delivery and deployment success evaluation</measure>
    <time_frame>during the index procedure</time_frame>
    <description>it includes the following qualitative variables:&#xD;
Delivery system evaluation&#xD;
Overall rate of vascular access complications (≤30 days)&#xD;
Rate of access failures&#xD;
Rate of deployment system difficulties or failures&#xD;
Rate of angulation tool usage&#xD;
Rate of arterial pressure reduction maneuver</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>o Micro-costing analysis</measure>
    <time_frame>0-3 years</time_frame>
    <description>direct cost assessment of the total related resources to the index procedure and during the follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>o Change in Health-Related Quality of Life (HRQoL) as assessed using the EuroQoL Group EQ-5D (EQ-5D-5L)</measure>
    <time_frame>0-3 years</time_frame>
    <description>assessment of the variations of the qualitty of life levels (EQ-5D-5L) pre and post procedure and during th total follow -up. There are 5 questions and 5 qualitative answers plus a numerical scale (from 0 to 100) related with the general health status.&#xD;
Numerical scale can be compared at any time of the study. Besides that, we will attribute a numerical value to the 5 qualitative answers (100 for the best/ 75, 50, 25 and 0 for the worse), and then will calculate the differences among different times during the study duration</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Thoracic Aorta</condition>
  <condition>Thoracic Aorta Aneurysm</condition>
  <condition>Thoracic Aorta Abnormality</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>thoracic endovascular repair</intervention_name>
    <description>Repair of thoracic aorta lesions with the application of a dedicatet stent-graft by endovascular way.</description>
    <other_name>TEVAR</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Elective and Urgent Thoracic aorta pathologies such as TAAs, pseudoaneurysms,&#xD;
        TBADs, BTAIs, PAUs and IMHs, are eligible for screening for participation in the study.&#xD;
&#xD;
        Only patients who meet all of the Inclusion Criteria and none of the Exclusion Criteria&#xD;
        will be enrolled&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male / female&#xD;
&#xD;
          2. Age between 18 and 90 years of age&#xD;
&#xD;
          3. Patient diagnosed with thoracic aorta pathology (TAA, TBAD, BTAI, PAU, IMH) suitable&#xD;
             for TEVAR with a C-TAG Active Control stent-graft; diagnosis must be confirmed by&#xD;
             contrast computed tomography angiography (CTA) or magnetic resonance imaging (MRI)&#xD;
             within 3 months of the planned implant procedure.&#xD;
&#xD;
          4. Proximal and distal aortic necks suitable for stent-graft placement (i.e., inner&#xD;
             diameter ranging between 16 and 42 mm)&#xD;
&#xD;
          5. Proximal and distal landing zones suitable for the stent-graft&#xD;
&#xD;
          6. Adequate vascular access for insertion of the delivery system&#xD;
&#xD;
          7. Written informed consent upon enrolment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Aneurysm/lesion location not accessible to the delivery system and stent placement&#xD;
&#xD;
          2. Arterial access size insufficient for delivery system entrance or impossibility to&#xD;
             perform a surgical access conduit&#xD;
&#xD;
          3. Treatment of lesion that would require a delivery system with usable length greater&#xD;
             than 90 cm&#xD;
&#xD;
          4. Excessive arterial disease precluding delivery system entrance or passage&#xD;
&#xD;
          5. Systemic infection&#xD;
&#xD;
          6. Arterial tortuosity not allowing passage of the delivery system&#xD;
&#xD;
          7. Arterial or aneurysm/lesion size incompatible with stent graft&#xD;
&#xD;
          8. Mycotic aneurysm/lesions&#xD;
&#xD;
          9. Massive thrombus&#xD;
&#xD;
         10. Bleeding diathesis&#xD;
&#xD;
         11. Any condition (medical or anatomic) which makes the patient not suitable for&#xD;
             endovascular repair according to the opinion of the investigator&#xD;
&#xD;
         12. Untreatable allergy or history of allergic reaction to radiographic contrast medium&#xD;
&#xD;
         13. Untreatable allergy or history of allergic reaction to anticoagulants&#xD;
&#xD;
         14. Hypersensitivity to any of the components of the C-TAG device&#xD;
&#xD;
         15. Participation in an investigational clinical study involving a new chemical entity or&#xD;
             medical device within 3 months or 1 year, respectively, prior to the planned procedure&#xD;
&#xD;
         16. Patient not willing to give consent for transmission of personal &quot;pseudonymised&quot; data&#xD;
&#xD;
         17. For females: pregnancy or lactation&#xD;
&#xD;
         18. Women of childbearing potential (not postmenopausal or surgically sterile) not willing&#xD;
             to use an effective method of contraception during the study. Effective methods are&#xD;
             hormonal contraceptives (e.g., oral, implanted, or injected), intrauterine device&#xD;
             (IUDs), and sexual abstinence.&#xD;
&#xD;
         19. Patient committed to an institution by virtue of an order issued either by the courts&#xD;
             or by an authority&#xD;
&#xD;
         20. Patient who is unable to comply with the requirements of the study or who in the&#xD;
             opinion of the investigator should not participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vincent RIAMBAU, MD. PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Endovascular Foundation</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>vincent RIAMBAU, MD,PhD</last_name>
    <phone>+34607958090</phone>
    <email>vriambau@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Santi Trimarchi, MD. PhD</last_name>
    <email>satrimarchi@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Santi Trimarchi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefano Bonardelli, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic of Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>vicente riambau, MD</last_name>
      <phone>607958090</phone>
      <email>vriambau@clinic.cat</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>September 18, 2021</last_update_submitted>
  <last_update_submitted_qc>September 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Endovascular Foundation</investigator_affiliation>
    <investigator_full_name>V. Riambau, MD, PhD</investigator_full_name>
    <investigator_title>Professor and chief of vascular surgery division</investigator_title>
  </responsible_party>
  <keyword>thoracic endograft</keyword>
  <keyword>direct cost</keyword>
  <keyword>safety</keyword>
  <keyword>efficacy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Dissection</mesh_term>
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm, Thoracic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Source data are defined as all information necessary for the reconstruction and evaluation of the Clinical Investigation.&#xD;
The Investigator will keep all study records, source data available for inspection by the CRO's monitors, EC and regulatory authorities.&#xD;
6.6. Study Records Retention The Investigator will maintain complete, accurate and current study records as required by applicable regulatory requirements. Records will be maintained during the study and for a minimum of 5 years.&#xD;
6.7. Publication Plan 6.7.1. It is the intent of the Promoter that the multicenter results of this study will be submitted for publication (in a peer reviewed journal). A publications committee will be established to review the multicenter results and develop publications at the completion of the study.</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/NCT04452240
org study id: EVF01
nct id: NCT04452240
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Study Design This is a prospective, multicenter, non-randomized clinical study in patients
      presenting thoracic aortic pathologies.

      Following a baseline assessment, the implantation procedure will be performed according to
      the Instructions for Use and local routine practice. A follow-up visit will be performed 30
      days, 6, 12,24 and 36 months after the implantation procedure.

      The investigator will perform assessments of the implantation procedure and device system and
      document adverse events (AE) and device deficiencies. Resources utilization and unit costs
      will be collected at index procedure and during follow-up. HRQoL is going to be investigated
      in this prospective study using the generic questionnaire EQ5D 5 levels, comparing pre- and
      postoperative scores.

      Study Objective The objective of the study is to evaluate the safety, performance and
      resource utilization associated with the use of GORE® TAG® Conformable Thoracic Stent Graft
      with ACTIVE CONTROL systems in humans having thoracic aortic pathologies. Safety will be
      evaluated considering mortality and morbidity variables (mainly focused on device related
      complications). Efficacy will be evaluated according to the variables related to the
      technical and clinical successes. In addition, resource utilization and associated costs will
      be collected prospectively with the objective to analyze differences in resource utilization
      between outcome groups, landing zone groups, disease severity groups, adverse event groups
      and case-mix groups. We will calculate the average marginal costs increase for complications
      when they occurred during TEVAR or surgical revascularization (e.g., paralysis, stroke, nerve
      injury, lymph damages, myocardial infarction, major bleeding event, respiratory
      complication). Resource utilization analysis is not going to be limited to the index
      procedure but will continue during follow-up.

      Subject Population: Elective and Urgent Thoracic aorta pathologies such as aneurysms,
      pseudoaneurysms, dissections, blunt thoracic aorta injury, penetrating ulcers and intramural
      hematoma.

      Planned number of patients: A total of 200 patients. Approx. 20 study centers in 2 European
      countries (15 in Italy and 5 in Spain) . A subgroup of 8centers will be selected for the
      micro-costing analysis (7 in Italy and one in Barcelona) Expected Time to Complete
      Enrollment: end of 2021 (18 months).
Brief Summary: Study Design This is a prospective, multicenter, non-randomized clinical study
      in patients presenting thoracic aortic pathologies.

      Following a baseline assessment, the implantation procedure will be performed according to
      the Instructions for Use and local routine practice. A follow-up visit will be performed 30
      days, 6, 12,24 and 36 months after the implantation procedure.

      The investigator will perform assessments of the implantation procedure and device system and
      document adverse events (AE) and device deficiencies. Resources utilization and unit costs
      will be collected at index procedure and during follow-up. HRQoL is going to be investigated
      in this prospective study using the generic questionnaire EQ5D 5 levels, comparing pre- and
      postoperative scores.

      Study Objective The objective of the study is to evaluate the safety, performance and
      resource utilization associated with the use of GORE® TAG® Conformable Thoracic Stent Graft
      with ACTIVE CONTROL systems in humans having thoracic aortic pathologies. Safety will be
      evaluated considering mortality and morbidity variables (mainly focused on device related
      complications). Efficacy will be evaluated according to the variables related to the
      technical and clinical successes. In addition, resource utilization and associated costs will
      be collected prospectively with the objective to analyze differences in resource utilization
      between outcome groups, landing zone groups, disease severity groups, adverse event groups
      and case-mix groups. The investigators will calculate the average marginal costs increase for
      complications when they occurred during TEVAR or surgical revascularization (e.g., paralysis,
      stroke, nerve injury, lymph damages, myocardial infarction, major bleeding event, respiratory
      complication). Resource utilization analysis is not going to be limited to the index
      procedure but will continue during follow-up.

      Subject Population: Elective and Urgent Thoracic aorta pathologies such as aneurysms,
      pseudoaneurysms, dissections, blunt thoracic aorta injury, penetrating ulcers and intramural
      hematoma.

      Planned number of patients: A total of 200 patients. Approx. 20 study centers in 2 European
      countries (15 in Italy and 5 in Spain) . A subgroup of 8centers will be selected for the
      micro-costing analysis (7 in Italy and one in Barcelona) Expected Time to Complete
      Enrollment: end of 2021 (18 months).

      Detailed Description: 1. Introduction 1.1. Disease1 A thoracic aortic aneurysm (TAA) and
      pseudoaneurysm Type B aortic dissection (TBAD) Intramural hematoma (IMH). IMH may be a
      precursor to both classic AD and penetrating aortic ulcer (PAU).

      Blunt thoracic aortic injury (BTAI) 1.3. Study Device Description GORE® TAG® Conformable
      Thoracic Stent Graft with ACTIVE CONTROL System is a device designed for the endovascular
      repair of TAAs, BTAIs, and TBADs of the thoracic aorta. The controlled deployment is designed
      to optimize accuracy, angulation, and apposition. Its conformability with enhanced control
      allows for optimized wall apposition even in the complex aortic anatomy 2. Study Objectives
      2.1. Primary Objective(s) The primary objective of CONFORTA Clinical study is to evaluate the
      safety, efficacy of the GORE® TAG® Conformable Thoracic Stent Graft for the treatment of
      patients with Thoracic Aortic pathologies.

      2.2. Secondary Objective(s) 2.2.1. Health Economic Data healthcare organizations must
      identify and address waste in healthcare and reduce the total cost of care. The secondary
      objective of this trial is focusing on patient-based costing (PBC).

      To provide patient care cost a micro-costing analysis (a cost estimation method that involves
      the direct enumeration and costing out of every input consumed in the treatment of a
      particular patient) will be conducted together with an assessment of patient QoL alongside
      the study data collection.

      2.2.2. Quality of Life data This health status information is collected before and after a
      procedure and provides an indication of the outcomes or quality of care delivered to the
      patient. Among different PROMs, the preference-based measure, such as the EQ-5D and Health
      Utilities Index, describes patients' responses to questions not to provide a score 3. Study
      Design 3.1. Description of Study Design This study is a prospective, multicenter,
      non-randomized single-arm study to evaluate the safety and efficacy of the GORE TAG
      Conformable Thoracic Stent Graft with ACTIVE CONTROL system for the treatment of patients
      descending Thoracic Aortic pathologies.

      Centers from Italy and Spain will be invited to participate to the study. A minimum of 20
      Clinical Sites (15 in Italy and 5 in Spain) will participate in this study with two hundred
      patients estimated in this study.

      Patients may be enrolled into the study provided all inclusion and no exclusion criteria are
      met as specified in Section 4. Subjects will be evaluated through hospital discharge and
      return for follow-up visits at 30 days, 6, 12, 24 and 36 months after the implantation
      procedure. The cost analysis is limited to the 7 Italian centers located in Region Lombardia
      and one in Barcelona (Hospital Clinic of Barcelona).

      3.2. Study Endpoints 3.2.1. Primary Endpoints

        -  Freedom from descending thoracic aorta-related mortality

        -  Delivery /deployment success of the study device systems

      This evaluation will include the following:

        -  evaluation of the delivery system

        -  overall rate of vascular access complications (≤30 days)

        -  rate of access failures

        -  rate of deployment system difficulties

        -  Rate of angulation tool usage

        -  Rate of arterial pressure reduction maneuver 3.2.2. Secondary study endpoints

        -  Micro-costing analysis

        -  Change in QoL from baseline 4. Study Population 4.1. Description of Population Patients
           with Elective and Urgent Thoracic aorta pathologies such as TAAs, pseudoaneurysms,
           TBADs, BTAIs, PAUs and IMHs, are eligible for screening for participation in the study.

      Only patients who meet all of the Inclusion Criteria and none of the Exclusion Criteria will
      be enrolled.

      4.2. Inclusion Criteria Described in another section 4.3. Exclusion criteria: Described in
      another section 5. Study Procedures/Evaluations Sites are required to use a CTA scan or MRI
      alternatively ultrasound to assess the inserted device, permeability and integrity. Each Site
      will be responsible for maintaining and calibrating the equipment used.

      5.1. Schedule of Events 5.2. Informed Consent Process All patients must provide informed
      consent prior to any study related procedures being performed. The case history (i.e., source
      documents/Subject chart) for each Subject shall document that such informed consent was
      obtained. The Ethical Committee (EC) approved consent form will be signed and personally
      dated by the Subject and the person who conducted the informed consent discussion. The
      original signed informed consent form will be retained in the Subject records. A copy of the
      informed consent document will be given to the Subject for their records.

      5.3. Baseline Prior to entry into this study, all patients will be screened for eligibility.
      Screening assessments may be performed over several days and to the day of implant. The
      following examinations will be performed and respective data recorded 5.4. Procedure The
      endovascular placement of the stent-graft will be performed as described in the Instructions
      for Use (contains details about techniques and methods for device deployment and
      implantation) and according to local practice at the site.

      5.5. Hospital discharge

      The patients will be discharged from the clinic at the discretion of the investigator after
      performance of the following assessments:

        -  Physical examination

        -  Documentation of duration of intensive care unit (ICU) admission

        -  The investigator will document all AE and relevant concomitant medication/procedures

        -  Resource consumption questionnaire 5.6. Follow-Up Subjects will be evaluated through
           hospital discharge and return for follow-up visits at 30 days, 6, 12, 24 and 36 months
           after the implantation procedure.

      5.7. Subject Withdrawal from the Study A Subject may withdraw from the study at any time and
      should notify the Investigator in this event. The Investigator may also withdraw the Subject
      from the study at any time based on his / her medical judgment.

      5.8. Subject Lost to Follow-Up A Subject will be considered lost to follow-up and withdrawn
      from the study once they have missed two consecutive follow-up visits and three documented
      attempts have been made by the Investigator or designee to contact the Subject or next of
      kin.

      5.9. Subject Study Completion A Subject has completed the study when final completion of all
      follow up visits are done. Any Subject that does not complete these requirements due to
      voluntary withdrawal, physician withdrawal, death, or any other reason will be considered a
      withdrawal..

      6. Study Administration 6.1. Monitoring Site monitoring for this study will be provided by
      CRO Leon Research S.L.

      6.2. Core Lab Core Lab services for this study will be provided by external independent
      observers provided by Endovascular Foundation. Core Lab assessment could be for all imaging
      morphometries related to 100% of the included cases or for a random sample, depending on the
      promoter final decision.

      6.3. Protocol Deviations A Protocol deviation is defined as any change, divergence, or
      departure from the study design or procedures of a research protocol. The Investigator is
      responsible for promptly recording and reporting Protocol Deviations to the local Ethical
      Committee.

      6.4. Protocol Amendments The Investigator will obtain EC approval on all amendments in a
      timely manner.

      6.5. Access to Source Data/Documents Source data are defined as all information necessary for
      the reconstruction and evaluation of the Clinical Investigation.

      The Investigator will keep all study records, source data available for inspection by the
      CRO's monitors, EC and regulatory authorities.

      6.6. Study Records Retention The Investigator will maintain complete, accurate and current
      study records as required by applicable regulatory requirements. Records will be maintained
      during the study and for a minimum of 5 years.

      6.7. Publication Plan It is the intent of the Promoter that the multicenter results of this
      study will be submitted for publication (in a peer reviewed journal). A publications
      committee will be established to review the multicenter results and develop publications at
      the completion of the study.

      7. Data Collection and Submission 7.1. Data Collection Methods The electronic data capture
      system (EDC system) for this study will be provided by Xolomon Tree S.L.

      7.2. Data Clarification and Correction by electronic queries 7.3. Case Report Form (CRF)
      Completion Schedule: 7.3.1. Baseline Demographics, clinical status and anatomical
      morphometrics should be provide to the data base manager prior to the inclusion and prior to
      the procedure 7.3.2. Procedural data should be provided with an acceptable window of 1 week
      after the index procedure 7.3.3. Follow-up data, Clinical and imaging information, at 1, 6,
      12 and 24 months will have an acceptable window of 14 days for 1 month and 30 days for the
      rest.

      7.3.4. Resource utilization information will be included in the CRF in combination with
      dedicated OR CRF 8. Risk Assessment The warnings and precautions when using the
      investigational device are described in detail in the Instructions for Use.

      8.1. Risk-to-Benefit Rationale Risks are inherent to the endovascular repair of the thoracic
      aorta. Benefits are related to the repair of the pathological entity. Risk / benefit should
      be assessed by the physician in charge, explained to the patient and accepted, by signed
      informed consent, by the patient or other legal representative.

      9. Adverse Events (AE) and Safety Monitoring 9.1. Anticipated AE Anticipated AE are
      complications that are known to be associated with thoracic aortic pathologies which are
      planned to undergo TEVAR with a stent-graft. See Section 8, Risk Assessment.

      9.2. Unanticipated Serious Adverse Device Effects (USADE) Serious adverse device effect which
      by its nature, incidence, severity or outcome has not been identified in the current version
      of the risk analysis report. NOTE: Anticipated: an effect which by its nature, incidence,
      severity or outcome has been previously identified in the risk analysis report.

      10. Statistical Analysis 10.1. Study Hypotheses The used thoracic endograft device, C-TAG
      active control, has high safety and effectiveness, in terms of very low rates of
      device-related complications, high accuracy on deployment and solution of the underlying
      pathology.

      10.2. Sample Size Assumptions A cohort of a minimum of 200 cases is enough to prove our
      hypothesis according to previous clinical reports with similar devices. Technical
      improvements will be easily assessed by experienced operators with large expertise with
      similar devices.

      10.3. Sample Size Determination That is a case series study. 200 cases are comparable with
      similar series already published in the literature with other similar devices for similar
      indications.

      10.4. Data Analysis 10.4.1. Timing of Analyses An interim clinical analysis can be considered
      when the sample will reach 50% of the final goal.

      10.4.2. Analysis Populations Consecutive patients with thoracic aorta pathology according to
      the inclusion and exclusion criteria previously described. The investigators will replace
      missing or removed cases in order to have the goal population included.

      10.4.3. Statistical Analysis of Primary Endpoint(s) Quantitative parameters will be described
      using the following summary descriptive statistics: number of non-missing values, mean,
      standard deviation, median, first and third quartiles, and minimum and maximum values.

      10.4.4. Statistical Analysis of Secondary Endpoint(s) The rate of MAEs will be assessed at 1
      year and following time points and will be derived as: all-cause death, bowel ischemia,
      myocardial infarction, paraplegia, renal failure, respiratory failure, and secondary
      endovascular procedure as defined in section 9, stroke, and procedural blood loss ≥1,000mL.

      11. Cost and QoL analysis 11.1. Micro-costing analysis Micro-costing analysis will be
      conducted to assess cost associated to each patient enrolled in the trial from the beginning
      of the hospitalization to the study follow-up in the perspective of the provider that need to
      consider budget constraints.
observational model: Case-Only
time perspective: Prospective
measure: • Freedom from descending thoracic aorta-related mortality
time frame: 0-3 years
description: Mortality rate related to the descending thoracic aorta condition or its endovascular repair or procedure
measure: • Delivery and deployment success evaluation
time frame: during the index procedure
description: it includes the following qualitative variables:
Delivery system evaluation
Overall rate of vascular access complications (≤30 days)
Rate of access failures
Rate of deployment system difficulties or failures
Rate of angulation tool usage
Rate of arterial pressure reduction maneuver
measure: o Micro-costing analysis
time frame: 0-3 years
description: direct cost assessment of the total related resources to the index procedure and during the follow-up
measure: o Change in Health-Related Quality of Life (HRQoL) as assessed using the EuroQoL Group EQ-5D (EQ-5D-5L)
time frame: 0-3 years
description: assessment of the variations of the qualitty of life levels (EQ-5D-5L) pre and post procedure and during th total follow -up. There are 5 questions and 5 qualitative answers plus a numerical scale (from 0 to 100) related with the general health status.
Numerical scale can be compared at any time of the study. Besides that, we will attribute a numerical value to the 5 qualitative answers (100 for the best/ 75, 50, 25 and 0 for the worse), and then will calculate the differences among different times during the study duration
intervention type: Device
intervention name: thoracic endovascular repair
description: Repair of thoracic aorta lesions with the application of a dedicatet stent-graft by endovascular way.
other name: TEVAR
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Vincent RIAMBAU, MD. PhD
role: Principal Investigator
affiliation: Endovascular Foundation
last name: vincent RIAMBAU, MD,PhD
phone: +34607958090
email: vriambau@gmail.com
last name: Santi Trimarchi, MD. PhD
email: satrimarchi@gmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Italy
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Endovascular Foundation
investigator full name: V. Riambau, MD, PhD
investigator title: Professor and chief of vascular surgery division
mesh term: Aortic Dissection
mesh term: Aneurysm
mesh term: Aortic Aneurysm
mesh term: Aortic Aneurysm, Thoracic
sharing ipd: No
ipd description: Source data are defined as all information necessary for the reconstruction and evaluation of the Clinical Investigation.
The Investigator will keep all study records, source data available for inspection by the CRO's monitors, EC and regulatory authorities.
6.6. Study Records Retention The Investigator will maintain complete, accurate and current study records as required by applicable regulatory requirements. Records will be maintained during the study and for a minimum of 5 years.
6.7. Publication Plan 6.7.1. It is the intent of the Promoter that the multicenter results of this study will be submitted for publication (in a peer reviewed journal). A publications committee will be established to review the multicenter results and develop publications at the completion of the study.