<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/NCT02989948</url>
  </required_header>
  <id_info>
    <org_study_id>D18194</org_study_id>
    <nct_id>NCT02989948</nct_id>
  </id_info>
  <brief_title>Physician-Modified Fenestrated and Branched Aortic Endografting for TAAA</brief_title>
  <official_title>Safety and Effectiveness of Physician-Modified Fenestrated and Branched Aortic Endografting for the Treatment of Thoracoabdominal Aortic Aneurysms (TAAA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>David P. Kuwayama</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary clinical objective of this study is to evaluate the safety and effectiveness of a&#xD;
      physician-modified, fenestrated and branched aortic endoprosthesis for the treatment of&#xD;
      thoracoabdominal aortic aneurysms (TAAAs). The goal of the primary analysis is to demonstrate&#xD;
      both the safety and effectiveness of using a physician-modified fenestrated Cook Zenith Alpha&#xD;
      Thoracic Endovascular Graft as compared to previously published results of open surgical&#xD;
      replacement of the aneurysmal aorta.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a prospective, two-arm, traditional feasibility study of a physician modified&#xD;
      fenestrated Cook Zenith Alpha Thoracic Endovascular Graft base device in adult patients&#xD;
      meeting traditional size criteria for open surgical treatment of thoracoabdominal aortic&#xD;
      aneurysms (TAAAs). Patients meriting surgical treatment of their aneurysm that also meet&#xD;
      inclusion and exclusion criteria will be eligible for enrollment. Patients will be followed&#xD;
      for 5 years post procedure. Major adverse events (MAEs) will also be recorded by the&#xD;
      Sponsor-Investigator (S-I) and will be monitored by a locally appointed Data Monitoring&#xD;
      Committee, Dartmouth-Hitchcock Health and the D-HH Human Research Protection Program IRB/IEC,&#xD;
      and the FDA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 22, 2020</start_date>
  <completion_date type="Anticipated">September 2029</completion_date>
  <primary_completion_date type="Actual">February 21, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>30 day survival</measure>
    <time_frame>30 Days</time_frame>
    <description>Percent of patients who survive 30 days following surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Major Adverse Events (MAE) at 30 days following surgery</measure>
    <time_frame>30 Days</time_frame>
    <description>Percent of patients who development major adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Treatment success at 12 months following surgery</measure>
    <time_frame>12 Months</time_frame>
    <description>Percent of patients achieving treatment success through 1 year</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Technical success at 12 months following surgery</measure>
    <time_frame>12 Months</time_frame>
    <description>Technical success is assessed 12 months following surgery and is defined as a composite of: successful delivery, without need for unanticipated corrective intervention related to delivery; successful and accurate deployment at the intended implantation site; and successful withdrawal, without need for unanticipated correct intervention related to withdrawal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Technical success on the day of surgery</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients achieving technical success on the day of surgery, defined as the composite of; successful delivery, successful and accurate deployment, successful withdrawal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aneurysm rupture</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients developing aneurysm rupture</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Conversion to open repair</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients necessitating conversion to open repair. This is assessed intraoperatively. In case of a device deployment failure or intraoperative aneurysm rupture, emergent conversion to open repair via laparotomy, thoracotomy, or thoracoabdominal aortic exposure may become necessary. Patients undergoing such intraoperative conversion will be considered to have met this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Access site complication (Femoral or Iliac)</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients suffering access site complication (femoral or iliac). If femoral or iliac rupture occurs intraoperatively, or if femoral or iliac flow-limiting dissection or occlusion is identified intraoperatively or on the day of surgery, patients will be considered to have met this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lower extremity ischemia</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients developing lower extremity ischemia. This will be assess intraoperatively and on the day of surgery. If patients have lower extremity pulses either absent or diminished compared to baseline, with associated pain, sensory deficits or motor deficits on clinical evaluation, patients will be considered to have met this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lower extremity compartment syndrome</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients developing lower extremity compartment syndrome. In patients with lower extremity pain to passive motion post-operatively, invasive pressure measurement of the four calf compartments will be performed. If compartment pressures are greater than 30 in any compartment, patients will be considered to have met this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients developing stroke - Modified Rankin Score (MRS) of 2 or greater). In patients with altered mental status or lateralizing motor or sensory deficits, MRI of the brain will be performed. If diffusion weighted MRI imaging demonstrates an intracranial lesion, a modified Rankin score will be calculated. If MRS is 2 or greater, patients will be considered to have met this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Paraplegia</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients developing paraplegia. Patients with complete absence of lower extremity motor function in one or both legs will be considered to have met this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Paraparesis</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients developing paraparesis. Patients will undergo lower extremity motor strength assessment post-operatively on a standard 0 to 5 scale. If greater than 0 but less than 5 in either extremity, patients will be considered to have met this outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death during surgery</measure>
    <time_frame>Day of Surgery</time_frame>
    <description>Percent of patients who die during surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival rate</measure>
    <time_frame>At 30, 183 days; 1, 2, 3, 4 and 5 years</time_frame>
    <description>Percent of patients who survive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major Adverse Events (MAEs)</measure>
    <time_frame>At 30, 183 days; 1, 2, 3, 4 and 5 years</time_frame>
    <description>Percent of patients that development MAEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment success</measure>
    <time_frame>At 30, 183 days; 2, 3, 4 and 5 years</time_frame>
    <description>Percent of patients achieving treatment success</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Aortic Aneurysm, Thoracoabdominal</condition>
  <arm_group>
    <arm_group_label>Main Arm - Physician-modified fenestrated endovascular graft</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Use of a physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expanded Access Arm - Physician-modified fenestrated endovascular graft.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Use of a physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal, thoracic, or abdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair in an expanded use population.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Physician-modified aortic endograft</intervention_name>
    <description>Use of physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair.</description>
    <arm_group_label>Expanded Access Arm - Physician-modified fenestrated endovascular graft.</arm_group_label>
    <arm_group_label>Main Arm - Physician-modified fenestrated endovascular graft</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        MAIN ARM - Inclusion Criteria:&#xD;
&#xD;
          1. Must be a man or woman 50 years of age or older by the date of informed consent.&#xD;
&#xD;
          2. Must have a thoracoabdominal aortic aneurysm of any Crawford classification (extent&#xD;
             I-V) that extends no more proximal than the left subclavian artery.&#xD;
&#xD;
          3. Must have an aneurysm size that meets standard indications for surgical repair (6.0 cm&#xD;
             in maximum diameter in the descending thoracic aorta, or 5.5 cm in maximum diameter in&#xD;
             the abdominal aorta).&#xD;
&#xD;
          4. Must be considered, in the judgment of the S-I, to be a high risk candidate for open&#xD;
             surgical repair.&#xD;
&#xD;
          5. Must not be a candidate for repair under the Instructions for Use of a commercially&#xD;
             available, FDA-approved endovascular graft.&#xD;
&#xD;
          6. Must be able to provide informed consent.&#xD;
&#xD;
          7. Must be able to comply with the five year study assessment schedule of events.&#xD;
&#xD;
          8. Must have a non-aneurysm-related life expectancy, in the judgment of the S-I, of&#xD;
             greater than 2 years.&#xD;
&#xD;
        MAIN ARM - Exclusion Criteria:&#xD;
&#xD;
          1. Aneurysm due to acute or chronic dissection, intramural hematoma, penetrating aortic&#xD;
             ulceration, pseudoaneurysm, mycotic aneurysm, or traumatic transection.&#xD;
&#xD;
          2. Ruptured or acutely symptomatic aortic aneurysm.&#xD;
&#xD;
          3. Known connective tissue disorder.&#xD;
&#xD;
          4. Imaging demonstrating any of the following:&#xD;
&#xD;
               -  Lack of 20 mm non-aneurysmal proximal seal zone (zone 3, or zone 2 with a&#xD;
                  carotid-subclavian bypass or transposition).&#xD;
&#xD;
               -  Lack of 15 mm non-aneurysmal distal seal zone(s) (aortic, common iliac, or&#xD;
                  external iliac).&#xD;
&#xD;
               -  Branch vessel target (renal, superior mesenteric, or celiac) &lt; 5 mm or &gt; 10 mm in&#xD;
                  average diameter.&#xD;
&#xD;
               -  Untreated left subclavian artery stenosis or occlusion.&#xD;
&#xD;
               -  Untreated unilateral or bilateral hypogastric artery occlusion.&#xD;
&#xD;
               -  Signs that the inferior mesenteric artery is indispensable.&#xD;
&#xD;
               -  Have branching, duplication, aneurysm, or untreatable stenosis of the celiac,&#xD;
                  superior mesenteric artery, or renal arteries that would preclude implantation of&#xD;
                  the investigational devices.&#xD;
&#xD;
          5. Known sensitivities or allergies to stainless steel, PTFE, polyester, polypropylene,&#xD;
             nitinol, or gold.&#xD;
&#xD;
          6. History of anaphylaxis to contrast, with inability to prophylax appropriately.&#xD;
&#xD;
          7. Have uncorrectable coagulopathy.&#xD;
&#xD;
          8. Have unstable angina.&#xD;
&#xD;
          9. Have a body habitus that would inhibit X-ray visualization of the aorta.&#xD;
&#xD;
         10. Have a major surgical or interventional procedure unrelated to the treatment of the&#xD;
             aneurysm planned ≤30 days of the endovascular repair.&#xD;
&#xD;
         11. Known to be participating in any other clinical study which may affect performance of&#xD;
             this device.&#xD;
&#xD;
         12. Known, visible, or suspected pregnancy, confirmed with a Urine Pregnancy Test (UPT)&#xD;
&#xD;
         13. Contraindication to oral antiplatelet therapy.&#xD;
&#xD;
         14. Prisoners or those on alternative sentencing.&#xD;
&#xD;
         15. Known systemic infection with potential for endovascular graft infection.&#xD;
&#xD;
         16. Anticipated need for MRI scanning within 3 months of insertion of investigational&#xD;
             product.&#xD;
&#xD;
         17. Other conditions or comorbidities that, in the opinion of the S-I, would exclude the&#xD;
             patient.&#xD;
&#xD;
        EXPANDED ACCESS ARM - Inclusion Criteria&#xD;
&#xD;
          1. Must be a man or woman 50 years of age or older by the date of informed consent&#xD;
&#xD;
          2. Must have a thoracic, thoracoabdominal, or abdominal aortic aneurysm that necessitates&#xD;
             coverage of one or more visceral vessels (celiac, superior mesenteric, or renals) for&#xD;
             establishment of proximal and/or distal seal.&#xD;
&#xD;
          3. Must have an aneurysm size that meets standard size indications for surgical repair&#xD;
             (6.0 cm in maximum diameter in the descending thoracic aorta, or 5.5 cm in maximum&#xD;
             diameter in the abdominal aorta); or, in the judgment of the S-I, has aneurysm&#xD;
             characteristics that portend a high risk of near-term rupture&#xD;
&#xD;
          4. Must be considered, in the judgement of the S-I, to be a high risk candidate for open&#xD;
             surgical repair&#xD;
&#xD;
          5. Must not be a candidate for repair under the Instructions for Use of a commercially&#xD;
             available, FDA-approved endovascular graft&#xD;
&#xD;
          6. Patient must be able to provide informed consent&#xD;
&#xD;
          7. Must be able to comply with the five year study assessment schedule of events&#xD;
&#xD;
          8. Must have a non-aneurysm-related life expectancy, in the judgement of the S-I, of&#xD;
             greater than 2 years&#xD;
&#xD;
        EXPANDED ACCESS ARM - Exclusion Criteria&#xD;
&#xD;
          1. Known or suspected mycotic aneurysm&#xD;
&#xD;
          2. Ruptured aneurysm with hemodynamic instability&#xD;
&#xD;
          3. Known connective tissue disorder&#xD;
&#xD;
          4. Imaging demonstrating any of the following:&#xD;
&#xD;
               -  Lack of 20 mm non-aneurysmal proximal seal zone (in either native aorta, elephant&#xD;
                  trunk graft, or aortic arch endograft)&#xD;
&#xD;
               -  Lack of 15 mm non-aneurysmal distal seal zone(s) (in either native aortoiliac&#xD;
                  vessels, prosthetic aortoiliac grafts, or aortoiliac endografts)&#xD;
&#xD;
               -  Branch vessel target (renal, superior mesenteric, or celiac) &gt; 10 mm in average&#xD;
                  diameter&#xD;
&#xD;
          5. Known sensitivities or allergies to stainless steel, PTFE, polyester, polypropylene,&#xD;
             nitinol, or gold&#xD;
&#xD;
          6. History of anaphylaxis to contrast, with inability to prophylax appropriately.&#xD;
&#xD;
          7. Have uncorrectable coagulopathy&#xD;
&#xD;
          8. Have a body habitus that would inhibit X-ray visualization of the aorta&#xD;
&#xD;
          9. Have a major surgical or interventional procedure unrelated to the treatment of the&#xD;
             aneurysm planned ≤ 30 days of the endovascular repair&#xD;
&#xD;
         10. Known to be participating in any other clinical study which may affect performance of&#xD;
             this device&#xD;
&#xD;
         11. Known, visible, or suspected pregnancy, confirmed with a Urine Pregnancy Test (UPT)&#xD;
&#xD;
         12. Contraindication to oral antiplatelet therapy&#xD;
&#xD;
         13. Prisoners or those on alternative sentencing&#xD;
&#xD;
         14. Known systemic infection with potential for endovascular graft infection&#xD;
&#xD;
         15. Anticipated need for MRI scanning within 3 months of insertion of investigational&#xD;
             product&#xD;
&#xD;
         16. Other conditions or comorbidities that, in the opinion of the S-I, would exclude the&#xD;
             patient&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David P. Kuwayama, M.D., M.P.A.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth-Hitchcock Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Crawford ES, Coselli JS. Thoracoabdominal aneurysm surgery. Semin Thorac Cardiovasc Surg. 1991 Oct;3(4):300-22. No abstract available.</citation>
    <PMID>1793767</PMID>
  </reference>
  <reference>
    <citation>Safi HJ, Miller CC 3rd. Spinal cord protection in descending thoracic and thoracoabdominal aortic repair. Ann Thorac Surg. 1999 Jun;67(6):1937-9; discussion 1953-8. doi: 10.1016/s0003-4975(99)00397-5.</citation>
    <PMID>10391343</PMID>
  </reference>
  <reference>
    <citation>Dapunt OE, Galla JD, Sadeghi AM, Lansman SL, Mezrow CK, de Asla RA, Quintana C, Wallenstein S, Ergin AM, Griepp RB. The natural history of thoracic aortic aneurysms. J Thorac Cardiovasc Surg. 1994 May;107(5):1323-32; discussion 1332-3.</citation>
    <PMID>8176976</PMID>
  </reference>
  <reference>
    <citation>Kuzmik GA, Sang AX, Elefteriades JA. Natural history of thoracic aortic aneurysms. J Vasc Surg. 2012 Aug;56(2):565-71. doi: 10.1016/j.jvs.2012.04.053.</citation>
    <PMID>22840907</PMID>
  </reference>
  <reference>
    <citation>Clouse WD, Hallett JW Jr, Schaff HV, Gayari MM, Ilstrup DM, Melton LJ 3rd. Improved prognosis of thoracic aortic aneurysms: a population-based study. JAMA. 1998 Dec 9;280(22):1926-9. doi: 10.1001/jama.280.22.1926.</citation>
    <PMID>9851478</PMID>
  </reference>
  <reference>
    <citation>Cowan JA Jr, Dimick JB, Henke PK, Rectenwald J, Stanley JC, Upchurch GR Jr. Epidemiology of aortic aneurysm repair in the United States from 1993 to 2003. Ann N Y Acad Sci. 2006 Nov;1085:1-10. doi: 10.1196/annals.1383.030.</citation>
    <PMID>17182917</PMID>
  </reference>
  <reference>
    <citation>O'Callaghan A, Mastracci TM, Eagleton MJ. Staged endovascular repair of thoracoabdominal aortic aneurysms limits incidence and severity of spinal cord ischemia. J Vasc Surg. 2015 Feb;61(2):347-354.e1. doi: 10.1016/j.jvs.2014.09.011. Epub 2014 Oct 23.</citation>
    <PMID>25449006</PMID>
  </reference>
  <reference>
    <citation>Lee JT, Lee GK, Chandra V, Dalman RL. Comparison of fenestrated endografts and the snorkel/chimney technique. J Vasc Surg. 2014 Oct;60(4):849-56; discussion 856-7. doi: 10.1016/j.jvs.2014.03.255. Epub 2014 Apr 27.</citation>
    <PMID>24785682</PMID>
  </reference>
  <reference>
    <citation>Greenberg R, Eagleton M, Mastracci T. Branched endografts for thoracoabdominal aneurysms. J Thorac Cardiovasc Surg. 2010 Dec;140(6 Suppl):S171-8. doi: 10.1016/j.jtcvs.2010.07.061.</citation>
    <PMID>21092788</PMID>
  </reference>
  <reference>
    <citation>Greenberg RK, Lu Q, Roselli EE, Svensson LG, Moon MC, Hernandez AV, Dowdall J, Cury M, Francis C, Pfaff K, Clair DG, Ouriel K, Lytle BW. Contemporary analysis of descending thoracic and thoracoabdominal aneurysm repair: a comparison of endovascular and open techniques. Circulation. 2008 Aug 19;118(8):808-17. doi: 10.1161/CIRCULATIONAHA.108.769695. Epub 2008 Aug 4.</citation>
    <PMID>18678769</PMID>
  </reference>
  <reference>
    <citation>Matsumura JS, Melissano G, Cambria RP, Dake MD, Mehta S, Svensson LG, Moore RD; Zenith TX2 Clinical Trial Investigators. Five-year results of thoracic endovascular aortic repair with the Zenith TX2. J Vasc Surg. 2014 Jul;60(1):1-10. doi: 10.1016/j.jvs.2014.01.043. Epub 2014 Mar 14.</citation>
    <PMID>24636714</PMID>
  </reference>
  <reference>
    <citation>Riga CV, McWilliams RG, Cheshire NJ. In situ fenestrations for the aortic arch and visceral segment: advances and challenges. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):161-5. doi: 10.1177/1531003510388421. Epub 2011 Apr 17.</citation>
    <PMID>21502107</PMID>
  </reference>
  <reference>
    <citation>Oderich GS, Greenberg RK. Endovascular iliac branch devices for iliac aneurysms. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):166-72. doi: 10.1177/1531003511408344. Epub 2011 Aug 1.</citation>
    <PMID>21810808</PMID>
  </reference>
  <reference>
    <citation>Chuter T, Greenberg RK. Standardized off-the-shelf components for multibranched endovascular repair of thoracoabdominal aortic aneurysms. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):195-201. doi: 10.1177/1531003511430397.</citation>
    <PMID>22205654</PMID>
  </reference>
  <reference>
    <citation>Oderich GS, Greenberg RK. The evolving options for endovascular repair of complex aortic aneurysms. Foreword. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):145-8. doi: 10.1177/1531003511407343. No abstract available.</citation>
    <PMID>22205653</PMID>
  </reference>
  <reference>
    <citation>O'Brien N, Sobocinski J, d'Elia P, Guillou M, Maioli F, Azzaoui R, Haulon S. Fenestrated endovascular repair of type IV thoracoabdominal aneurysms: device design and implantation technique. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):173-7. doi: 10.1177/1531003511408340. Epub 2011 Aug 1.</citation>
    <PMID>21810817</PMID>
  </reference>
  <reference>
    <citation>Browne TF, Hartley D, Purchas S, Rosenberg M, Van Schie G, Lawrence-Brown M. A fenestrated covered suprarenal aortic stent. Eur J Vasc Endovasc Surg. 1999 Nov;18(5):445-9. doi: 10.1053/ejvs.1999.0924.</citation>
    <PMID>10610834</PMID>
  </reference>
  <reference>
    <citation>Haulon S, D'Elia P, O'Brien N, Sobocinski J, Perrot C, Lerussi G, Koussa M, Azzaoui R. Endovascular repair of thoracoabdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2010 Feb;39(2):171-8. doi: 10.1016/j.ejvs.2009.11.009. Epub 2009 Nov 27.</citation>
    <PMID>19945316</PMID>
  </reference>
  <reference>
    <citation>Starnes BW. Physician-modified endovascular grafts for the treatment of elective, symptomatic, or ruptured juxtarenal aortic aneurysms. J Vasc Surg. 2012 Sep;56(3):601-7. doi: 10.1016/j.jvs.2012.02.011. Epub 2012 May 2.</citation>
    <PMID>22554425</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>David P. Kuwayama</investigator_full_name>
    <investigator_title>Staff Physician, Vascular Surgery</investigator_title>
  </responsible_party>
  <keyword>endovascular</keyword>
  <keyword>physician-modified</keyword>
  <keyword>graft</keyword>
  <keyword>fenestration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm, Thoracoabdominal</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plan to share individual participant data (IPD) exists at this time.</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/NCT02989948
org study id: D18194
nct id: NCT02989948
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The primary clinical objective of this study is to evaluate the safety and effectiveness of a
      physician-modified, fenestrated and branched aortic endoprosthesis for the treatment of
      thoracoabdominal aortic aneurysms (TAAAs). The goal of the primary analysis is to demonstrate
      both the safety and effectiveness of using a physician-modified fenestrated Cook Zenith Alpha
      Thoracic Endovascular Graft as compared to previously published results of open surgical
      replacement of the aneurysmal aorta.
This study is a prospective, two-arm, traditional feasibility study of a physician modified
      fenestrated Cook Zenith Alpha Thoracic Endovascular Graft base device in adult patients
      meeting traditional size criteria for open surgical treatment of thoracoabdominal aortic
      aneurysms (TAAAs). Patients meriting surgical treatment of their aneurysm that also meet
      inclusion and exclusion criteria will be eligible for enrollment. Patients will be followed
      for 5 years post procedure. Major adverse events (MAEs) will also be recorded by the
      Sponsor-Investigator (S-I) and will be monitored by a locally appointed Data Monitoring
      Committee, Dartmouth-Hitchcock Health and the D-HH Human Research Protection Program IRB/IEC,
      and the FDA.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 30 day survival
time frame: 30 Days
description: Percent of patients who survive 30 days following surgery
measure: Major Adverse Events (MAE) at 30 days following surgery
time frame: 30 Days
description: Percent of patients who development major adverse events
measure: Treatment success at 12 months following surgery
time frame: 12 Months
description: Percent of patients achieving treatment success through 1 year
measure: Technical success at 12 months following surgery
time frame: 12 Months
description: Technical success is assessed 12 months following surgery and is defined as a composite of: successful delivery, without need for unanticipated corrective intervention related to delivery; successful and accurate deployment at the intended implantation site; and successful withdrawal, without need for unanticipated correct intervention related to withdrawal.
measure: Technical success on the day of surgery
time frame: Day of Surgery
description: Percent of patients achieving technical success on the day of surgery, defined as the composite of; successful delivery, successful and accurate deployment, successful withdrawal.
measure: Aneurysm rupture
time frame: Day of Surgery
description: Percent of patients developing aneurysm rupture
measure: Conversion to open repair
time frame: Day of Surgery
description: Percent of patients necessitating conversion to open repair. This is assessed intraoperatively. In case of a device deployment failure or intraoperative aneurysm rupture, emergent conversion to open repair via laparotomy, thoracotomy, or thoracoabdominal aortic exposure may become necessary. Patients undergoing such intraoperative conversion will be considered to have met this endpoint.
measure: Access site complication (Femoral or Iliac)
time frame: Day of Surgery
description: Percent of patients suffering access site complication (femoral or iliac). If femoral or iliac rupture occurs intraoperatively, or if femoral or iliac flow-limiting dissection or occlusion is identified intraoperatively or on the day of surgery, patients will be considered to have met this outcome.
measure: Lower extremity ischemia
time frame: Day of Surgery
description: Percent of patients developing lower extremity ischemia. This will be assess intraoperatively and on the day of surgery. If patients have lower extremity pulses either absent or diminished compared to baseline, with associated pain, sensory deficits or motor deficits on clinical evaluation, patients will be considered to have met this outcome.
measure: Lower extremity compartment syndrome
time frame: Day of Surgery
description: Percent of patients developing lower extremity compartment syndrome. In patients with lower extremity pain to passive motion post-operatively, invasive pressure measurement of the four calf compartments will be performed. If compartment pressures are greater than 30 in any compartment, patients will be considered to have met this outcome.
measure: Stroke
time frame: Day of Surgery
description: Percent of patients developing stroke - Modified Rankin Score (MRS) of 2 or greater). In patients with altered mental status or lateralizing motor or sensory deficits, MRI of the brain will be performed. If diffusion weighted MRI imaging demonstrates an intracranial lesion, a modified Rankin score will be calculated. If MRS is 2 or greater, patients will be considered to have met this outcome.
measure: Paraplegia
time frame: Day of Surgery
description: Percent of patients developing paraplegia. Patients with complete absence of lower extremity motor function in one or both legs will be considered to have met this outcome.
measure: Paraparesis
time frame: Day of Surgery
description: Percent of patients developing paraparesis. Patients will undergo lower extremity motor strength assessment post-operatively on a standard 0 to 5 scale. If greater than 0 but less than 5 in either extremity, patients will be considered to have met this outcome.
measure: Death during surgery
time frame: Day of Surgery
description: Percent of patients who die during surgery
measure: Survival rate
time frame: At 30, 183 days; 1, 2, 3, 4 and 5 years
description: Percent of patients who survive
measure: Major Adverse Events (MAEs)
time frame: At 30, 183 days; 1, 2, 3, 4 and 5 years
description: Percent of patients that development MAEs
measure: Treatment success
time frame: At 30, 183 days; 2, 3, 4 and 5 years
description: Percent of patients achieving treatment success
arm group label: Main Arm - Physician-modified fenestrated endovascular graft
arm group type: Experimental
description: Use of a physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair.
arm group label: Expanded Access Arm - Physician-modified fenestrated endovascular graft.
arm group type: Experimental
description: Use of a physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal, thoracic, or abdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair in an expanded use population.
intervention type: Device
intervention name: Physician-modified aortic endograft
description: Use of physician-modified fenestrated Cook Zenith Alpha Thoracic Endovascular Graft for the endovascular treatment of asymptomatic, non-ruptured thoracoabdominal aortic aneurysms of any Crawford extent (I-V) meeting traditional size criteria for open surgical repair.
arm group label: Expanded Access Arm - Physician-modified fenestrated endovascular graft.
arm group label: Main Arm - Physician-modified fenestrated endovascular graft
criteria: 
gender: All
minimum age: 50 Years
maximum age: 95 Years
healthy volunteers: No
last name: David P. Kuwayama, M.D., M.P.A.
role: Principal Investigator
affiliation: Dartmouth-Hitchcock Medical Center
facility: 
country: United States
citation: Crawford ES, Coselli JS. Thoracoabdominal aneurysm surgery. Semin Thorac Cardiovasc Surg. 1991 Oct;3(4):300-22. No abstract available.
PMID: 1793767
citation: Safi HJ, Miller CC 3rd. Spinal cord protection in descending thoracic and thoracoabdominal aortic repair. Ann Thorac Surg. 1999 Jun;67(6):1937-9; discussion 1953-8. doi: 10.1016/s0003-4975(99)00397-5.
PMID: 10391343
citation: Dapunt OE, Galla JD, Sadeghi AM, Lansman SL, Mezrow CK, de Asla RA, Quintana C, Wallenstein S, Ergin AM, Griepp RB. The natural history of thoracic aortic aneurysms. J Thorac Cardiovasc Surg. 1994 May;107(5):1323-32; discussion 1332-3.
PMID: 8176976
citation: Kuzmik GA, Sang AX, Elefteriades JA. Natural history of thoracic aortic aneurysms. J Vasc Surg. 2012 Aug;56(2):565-71. doi: 10.1016/j.jvs.2012.04.053.
PMID: 22840907
citation: Clouse WD, Hallett JW Jr, Schaff HV, Gayari MM, Ilstrup DM, Melton LJ 3rd. Improved prognosis of thoracic aortic aneurysms: a population-based study. JAMA. 1998 Dec 9;280(22):1926-9. doi: 10.1001/jama.280.22.1926.
PMID: 9851478
citation: Cowan JA Jr, Dimick JB, Henke PK, Rectenwald J, Stanley JC, Upchurch GR Jr. Epidemiology of aortic aneurysm repair in the United States from 1993 to 2003. Ann N Y Acad Sci. 2006 Nov;1085:1-10. doi: 10.1196/annals.1383.030.
PMID: 17182917
citation: O'Callaghan A, Mastracci TM, Eagleton MJ. Staged endovascular repair of thoracoabdominal aortic aneurysms limits incidence and severity of spinal cord ischemia. J Vasc Surg. 2015 Feb;61(2):347-354.e1. doi: 10.1016/j.jvs.2014.09.011. Epub 2014 Oct 23.
PMID: 25449006
citation: Lee JT, Lee GK, Chandra V, Dalman RL. Comparison of fenestrated endografts and the snorkel/chimney technique. J Vasc Surg. 2014 Oct;60(4):849-56; discussion 856-7. doi: 10.1016/j.jvs.2014.03.255. Epub 2014 Apr 27.
PMID: 24785682
citation: Greenberg R, Eagleton M, Mastracci T. Branched endografts for thoracoabdominal aneurysms. J Thorac Cardiovasc Surg. 2010 Dec;140(6 Suppl):S171-8. doi: 10.1016/j.jtcvs.2010.07.061.
PMID: 21092788
citation: Greenberg RK, Lu Q, Roselli EE, Svensson LG, Moon MC, Hernandez AV, Dowdall J, Cury M, Francis C, Pfaff K, Clair DG, Ouriel K, Lytle BW. Contemporary analysis of descending thoracic and thoracoabdominal aneurysm repair: a comparison of endovascular and open techniques. Circulation. 2008 Aug 19;118(8):808-17. doi: 10.1161/CIRCULATIONAHA.108.769695. Epub 2008 Aug 4.
PMID: 18678769
citation: Matsumura JS, Melissano G, Cambria RP, Dake MD, Mehta S, Svensson LG, Moore RD; Zenith TX2 Clinical Trial Investigators. Five-year results of thoracic endovascular aortic repair with the Zenith TX2. J Vasc Surg. 2014 Jul;60(1):1-10. doi: 10.1016/j.jvs.2014.01.043. Epub 2014 Mar 14.
PMID: 24636714
citation: Riga CV, McWilliams RG, Cheshire NJ. In situ fenestrations for the aortic arch and visceral segment: advances and challenges. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):161-5. doi: 10.1177/1531003510388421. Epub 2011 Apr 17.
PMID: 21502107
citation: Oderich GS, Greenberg RK. Endovascular iliac branch devices for iliac aneurysms. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):166-72. doi: 10.1177/1531003511408344. Epub 2011 Aug 1.
PMID: 21810808
citation: Chuter T, Greenberg RK. Standardized off-the-shelf components for multibranched endovascular repair of thoracoabdominal aortic aneurysms. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):195-201. doi: 10.1177/1531003511430397.
PMID: 22205654
citation: Oderich GS, Greenberg RK. The evolving options for endovascular repair of complex aortic aneurysms. Foreword. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):145-8. doi: 10.1177/1531003511407343. No abstract available.
PMID: 22205653
citation: O'Brien N, Sobocinski J, d'Elia P, Guillou M, Maioli F, Azzaoui R, Haulon S. Fenestrated endovascular repair of type IV thoracoabdominal aneurysms: device design and implantation technique. Perspect Vasc Surg Endovasc Ther. 2011 Sep;23(3):173-7. doi: 10.1177/1531003511408340. Epub 2011 Aug 1.
PMID: 21810817
citation: Browne TF, Hartley D, Purchas S, Rosenberg M, Van Schie G, Lawrence-Brown M. A fenestrated covered suprarenal aortic stent. Eur J Vasc Endovasc Surg. 1999 Nov;18(5):445-9. doi: 10.1053/ejvs.1999.0924.
PMID: 10610834
citation: Haulon S, D'Elia P, O'Brien N, Sobocinski J, Perrot C, Lerussi G, Koussa M, Azzaoui R. Endovascular repair of thoracoabdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2010 Feb;39(2):171-8. doi: 10.1016/j.ejvs.2009.11.009. Epub 2009 Nov 27.
PMID: 19945316
citation: Starnes BW. Physician-modified endovascular grafts for the treatment of elective, symptomatic, or ruptured juxtarenal aortic aneurysms. J Vasc Surg. 2012 Sep;56(3):601-7. doi: 10.1016/j.jvs.2012.02.011. Epub 2012 May 2.
PMID: 22554425
responsible party type: Sponsor-Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: David P. Kuwayama
investigator title: Staff Physician, Vascular Surgery
mesh term: Aneurysm
mesh term: Aortic Aneurysm
mesh term: Aortic Aneurysm, Thoracoabdominal
sharing ipd: No
ipd description: No plan to share individual participant data (IPD) exists at this time.