<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/NCT04471181</url>
  </required_header>
  <id_info>
    <org_study_id>GRAND study</org_study_id>
    <nct_id>NCT04471181</nct_id>
  </id_info>
  <brief_title>Greek Study for Endovascular Repair of Ruptured Abdominal Aortic Aneuryms</brief_title>
  <acronym>GRAND</acronym>
  <official_title>Greek Ruptured Aneurysm Endovascular Repair Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kostantinos Papazoglou</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medtronic</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aristotle University Of Thessaloniki</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ippokrateio General Hospital of Thessaloniki</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a non-randomized, prospective, observational multi-center research study. Its&#xD;
      purpose will be to assess the mortality and outcome of EVAR in patients with rAAA. As&#xD;
      mentioned in the introduction, EVAR approach for ruptured bdominal aortic aneurysms is&#xD;
      nowdays common clinical practice in many vascular centers , and the main treatment option in&#xD;
      Hippokrateio General hospital. The same applies in all future participating vascular centers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ruptured abdominal aortic aneurysms (rAAAs) remain one of the most emergent medical events,&#xD;
      with over 90% mortality if left untreated and a prevalence of a minimum 45 patients per&#xD;
      1000000 population. The 30 day mortality for emergency open repair has remained at around&#xD;
      50%, and there is no consistent improvement in the outcome of the open technique over time.&#xD;
      Since its development, endovascular aneurysm repair (EVAR), has been increasingly used even&#xD;
      in the emergency setting.&#xD;
&#xD;
      So far there have been 4 randomized controlled trials, comparing EVAR versus open repair for&#xD;
      rAAA. The first was a small trial from Nottingham followed by the Dutch trial AJAX and the&#xD;
      French ECAR. The last and biggest trial with 613 patients was the UK IMPROVE trial. All these&#xD;
      trials showed non inferiority of EVAR, but failed to prove benefit for EVAR with respect to&#xD;
      30 day mortality. Furthermore two meta-analysisof the above RCTs, stated again, that 30 and&#xD;
      90 day mortality is similar between EVAR and open surgery, with the exception of women having&#xD;
      a better outcome with an endovascular approach.&#xD;
&#xD;
      On the contrary, multiple observational studies and registries showed even a 50% risk&#xD;
      reduction in mortality with EVAR. There has been huge critique and discussion of the results&#xD;
      in IMPROVE trial, in which 10% of patients crossed over to the non-allocated treatment group.&#xD;
      In both groups, patients who were treated with EVAR had a mortality of 25%, significantly&#xD;
      lower than those who received open surgery (38%). Furthermore, two recent published studies&#xD;
      that compared mortality of rAAA between Sweden, USA and UK, came to the conclusion that&#xD;
      mortality is lower in centers that accept a large number of cases with rAAA, mostly treated&#xD;
      with EVAR. There is an argument that these encouraging results are subject of bias, since&#xD;
      there is patient selection according to haemodynamic stability and aortic morphology. A valid&#xD;
      counter argument stated by Lachat and colleagues is that EVAR for rAAA in their center, in&#xD;
      the moderate risk, stable patient with favourable anatomy (aortic neck length &gt;10mm) has a&#xD;
      reduced 30 day mortality of 10%, a result never demonstrated with open repair. As EVAR&#xD;
      evolves, new technical features of the devices may address the current limitations of the&#xD;
      technique. In addition, the anatomic suitability obstacle for EVAR has been revoked by the&#xD;
      PROTAGORAS study, which led to CE mark for a commercial stent graft system, allowing&#xD;
      treatment of aortic neck lengths as small as 2mm with the use of chimney technique. The&#xD;
      authors in the IMPROVE trial acknowledge the fact that: &quot;The suitability of ruptured aneurym&#xD;
      for EVAR is subjective and will be defined by the aortic morphology, the experience of the&#xD;
      operator and the range of resuscitation, endovascular and anaesthetic techniques available&quot;.&#xD;
&#xD;
      It is safe to guess that haemodynamically compromised patients would benefit from a less&#xD;
      invasive procedure, with minimum surgical exposure, if any, and local anaesthesia. There is&#xD;
      no doubt however that for a center to adopt an EVAR only policy, poses many logistical&#xD;
      challenges.&#xD;
&#xD;
      The aim for this research study is that an &quot;EVAR first&quot; approach is feasible in rAAA, even in&#xD;
      more complex anatomies and in patients with less physiologic reserve and at the same time&#xD;
      prove that short and midterm mortality and morbidity with EVAR is significantly lower than&#xD;
      open repair when compared to the mortality and morbidity rates of patients receiving open&#xD;
      repair in the latest RCT &quot;IMPROVE&quot;. This can be achieved, with implementing a treatment&#xD;
      alogorithm for the pre intra and post operative time, based on already established protocols&#xD;
      and relevant international standards, with single aim to avoid the factors in patient&#xD;
      management that contribute to mortality and morbidity. Furthermore this research study will&#xD;
      show increased applicability of EVAR in ruptured AAAs with shorter and larger in diameter&#xD;
      proximal neck and with angulation &gt;60 degrees, with the implementation of EndoAnchors&#xD;
      (HeliFX). Another aim for this research study is to identify the role of the clotting&#xD;
      mechanism in the overall mortality and thus to distinguish patient clotting profiles that can&#xD;
      predict or alter the outcome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2020</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">February 2022</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Mortality Rate</measure>
    <time_frame>30 days</time_frame>
    <description>Any cause mortality after EVAR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from rupture to diagnosis</measure>
    <time_frame>pre-intervention</time_frame>
    <description>In minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from diagnosis to intervention</measure>
    <time_frame>pre-intervention</time_frame>
    <description>In minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of procedures converted to open repair</measure>
    <time_frame>24 hours post-operatively</time_frame>
    <description>Any reason for conversion to open repair</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total mortality rate</measure>
    <time_frame>12 months post-operatively</time_frame>
    <description>All cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Major Adverse Events (MAE)</measure>
    <time_frame>30 days, 3 months and 12 months</time_frame>
    <description>MAE include :bowel ischaemia, myocardial infraction, paraplegia, renal failure, stroke, abdominal compartment syndrome, lower limb ischeamia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Endoleaks</measure>
    <time_frame>immediately after the procedure, 3 months after the procedure, 12 months after the procedure</time_frame>
    <description>Any endoleak observed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Graft related complications</measure>
    <time_frame>12 months after the procedure</time_frame>
    <description>Any graft related complication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibrinogel levels</measure>
    <time_frame>Pre-intervention, 24 hours after the procedure, 3 months after the procedure,12 months after the procedure</time_frame>
    <description>Fibrinogen levels mg/dL</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">157</enrollment>
  <condition>Rupture, Aortic</condition>
  <condition>Aneurysm, Abdominal Aortic</condition>
  <condition>Aneurysm, Ruptured</condition>
  <arm_group>
    <arm_group_label>All patients with ruptured abdominal aortic aneurysms</arm_group_label>
    <description>All patients will undergo CTA to confirm the diagnosis. The use of balloon for aortic clamp in case of haemodynamic instability can be used.&#xD;
All patients included in the research study must undergo standard EVAR with a bifurcated graft or an aorto-uni-iliac and a femoral to femoral crossover. In aneurysms with short proximal neck down to 4mm, or in cases where completion angiography indicates type Ia endoleak, the Heli-FX EndoAnchor system is recommended to be used, as indicated. All patients will have plain abdominal x-rays on discharge. Participants will undergo CTA in 3months and annually post-op.. In case of an adverse event before the 3 months follow up CTA, a more urgent imaging might be requested and proceed to appropriate action according to the findings.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Endovascular repair of ruptured abdominal aortic aneurysm (EVAR) with Medtronic Endurant</intervention_name>
    <description>Endovascular repair (EVAR) of ruptured abdominal aortic aneurysms with Medtronic Endurant II, and IIs device</description>
    <arm_group_label>All patients with ruptured abdominal aortic aneurysms</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive alive patients with true ruptured abdominal aortic aneurysm and anatomic&#xD;
        suitability for EVAR&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All alive patients admitted with rAAA and have anatomic suitability for EVAR according&#xD;
             to manufacturer's IFU. More accurately the anatomic criteria for the research study&#xD;
             are :&#xD;
&#xD;
               -  Neck diameter &gt;17mm, &lt; 32mm&#xD;
&#xD;
               -  Angle between the suprarenal aorta and the juxtarenal aorta &lt;60 degrees&#xD;
&#xD;
               -  Angle between the juxtarenal aorta and the long axis of the aneurysm sac &lt;90&#xD;
                  degrees&#xD;
&#xD;
               -  Neck length &gt;10mm&#xD;
&#xD;
               -  Neck length &lt;10mm down to 4mm with Heli-FX EndoAnchor system&#xD;
&#xD;
               -  Adequate aortic bifurcation diameter in case of a bifurcated graft&#xD;
&#xD;
               -  Bilateral Iliac luminal diameter &gt;7mm&#xD;
&#xD;
        The vascular surgeon in charge will make the ultimate decision on suitability. All&#xD;
        consecutive rAAAs treated with Endurant will be collected to avoid selection bias. No other&#xD;
        criteria (e.g, mental illness, dementia, old age, comorbidities) will be applied to decline&#xD;
        treatment and inclusion to the protocol. The final inclusion criterion will be that any&#xD;
        vascular surgeon participating in the research study, must have carried out a minimum of 20&#xD;
        EVAR procedures for asymptomatic/symptomatic AAA. Apart from the initial 6 centers more&#xD;
        centers can be implemented in the research study in the future.&#xD;
&#xD;
        AAA rupture will be confirmed and defined with computed tomography angiography (CTA).&#xD;
        Rupture will be rated as free intraperitoneal rupture (free rupture), definite contrast&#xD;
        extravasation and haematoma around the aorta (retroperitoneal rupture) and haematoma&#xD;
        surrounding the aorta without definite contrast leak (contained rupture)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptomatic non ruptured AAAs will not be included even when treated as emergencies.&#xD;
             Thoracoabdominal aneurysms and aortic dissections will also be excluded from the&#xD;
             research study. Juxtarenal ruptured AAA treated with standard EVAR without chimney&#xD;
             technique, outside IFU will also be excluded from the research study.However all&#xD;
             consecutive rAAAs in the participating centers will be collected in a screening CRF to&#xD;
             understand if this relates to rEVAR applicability.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kostantinos Papazoglou, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aristotle University Of Thessaloniki</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kostantinos Papazoglou, Professor</last_name>
    <phone>00306944582211</phone>
    <email>kpapas@auth.gr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ioakeim Giagtzidis, Consultant</last_name>
    <phone>00306979666129</phone>
    <email>kimisnet@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ippokrateio General Hospital</name>
      <address>
        <city>Thessaloníki</city>
        <state>Macedonia</state>
        <zip>54642</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Konstantinos Papazoglou, Prof</last_name>
      <phone>00306944582211</phone>
      <email>kpapas@auth.gr</email>
    </contact>
    <investigator>
      <last_name>Christos Karkos, Ass Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ioakeim Giagtzidis, Vasc Surg</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <reference>
    <citation>IMPROVE Trial Investigators; Powell JT, Sweeting MJ, Thompson MM, Ashleigh R, Bell R, Gomes M, Greenhalgh RM, Grieve R, Heatley F, Hinchliffe RJ, Thompson SG, Ulug P. Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial. BMJ. 2014 Jan 13;348:f7661. doi: 10.1136/bmj.f7661.</citation>
    <PMID>24418950</PMID>
  </reference>
  <reference>
    <citation>Hinchliffe RJ, Bruijstens L, MacSweeney ST, Braithwaite BD. A randomised trial of endovascular and open surgery for ruptured abdominal aortic aneurysm - results of a pilot study and lessons learned for future studies. Eur J Vasc Endovasc Surg. 2006 Nov;32(5):506-13; discussion 514-5. doi: 10.1016/j.ejvs.2006.05.016. Epub 2006 Aug 1.</citation>
    <PMID>16887369</PMID>
  </reference>
  <reference>
    <citation>Reimerink JJ, Hoornweg LL, Vahl AC, Wisselink W, van den Broek TA, Legemate DA, Reekers JA, Balm R; Amsterdam Acute Aneurysm Trial Collaborators. Endovascular repair versus open repair of ruptured abdominal aortic aneurysms: a multicenter randomized controlled trial. Ann Surg. 2013 Aug;258(2):248-56. doi: 10.1097/SLA.0b013e31828d4b76.</citation>
    <PMID>23549424</PMID>
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    <citation>Desgranges P, Kobeiter H, Katsahian S, Bouffi M, Gouny P, Favre JP, Alsac JM, Sobocinski J, Julia P, Alimi Y, Steinmetz E, Haulon S, Alric P, Canaud L, Castier Y, Jean-Baptiste E, Hassen-Khodja R, Lermusiaux P, Feugier P, Destrieux-Garnier L, Charles-Nelson A, Marzelle J, Majewski M, Bourmaud A, Becquemin JP; ECAR Investigators. Editor's Choice - ECAR (Endovasculaire ou Chirurgie dans les Anevrysmes aorto-iliaques Rompus): A French Randomized Controlled Trial of Endovascular Versus Open Surgical Repair of Ruptured Aorto-iliac Aneurysms. Eur J Vasc Endovasc Surg. 2015 Sep;50(3):303-10. doi: 10.1016/j.ejvs.2015.03.028. Epub 2015 May 20.</citation>
    <PMID>26001320</PMID>
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  <reference>
    <citation>van Beek SC, Conijn AP, Koelemay MJ, Balm R. Editor's Choice - Endovascular aneurysm repair versus open repair for patients with a ruptured abdominal aortic aneurysm: a systematic review and meta-analysis of short-term survival. Eur J Vasc Endovasc Surg. 2014 Jun;47(6):593-602. doi: 10.1016/j.ejvs.2014.03.003. Epub 2014 Apr 18.</citation>
    <PMID>24746873</PMID>
  </reference>
  <reference>
    <citation>Sweeting MJ, Balm R, Desgranges P, Ulug P, Powell JT; Ruptured Aneurysm Trialists. Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm. Br J Surg. 2015 Sep;102(10):1229-39. doi: 10.1002/bjs.9852. Epub 2015 Jun 24.</citation>
    <PMID>26104471</PMID>
  </reference>
  <reference>
    <citation>Karthikesalingam A, Holt PJ, Vidal-Diez A, Ozdemir BA, Poloniecki JD, Hinchliffe RJ, Thompson MM. Mortality from ruptured abdominal aortic aneurysms: clinical lessons from a comparison of outcomes in England and the USA. Lancet. 2014 Mar 15;383(9921):963-9. doi: 10.1016/S0140-6736(14)60109-4.</citation>
    <PMID>24629298</PMID>
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    <citation>Karthikesalingam A, Wanhainen A, Holt PJ, Vidal-Diez A, Brownrigg JR, Shpitser I, Bjorck M, Thompson MM, Mani K. Comparison of long-term mortality after ruptured abdominal aortic aneurysm in England and Sweden. Br J Surg. 2016 Feb;103(3):199-206. doi: 10.1002/bjs.10049. Epub 2015 Dec 1.</citation>
    <PMID>26620854</PMID>
  </reference>
  <reference>
    <citation>Vogel TR, Dombrovskiy VY, Haser PB, Graham AM. Has the implementation of EVAR for ruptured AAA improved outcomes? Vasc Endovascular Surg. 2009 Jun-Jul;43(3):252-7. doi: 10.1177/1538574408329271. Epub 2009 Jan 8.</citation>
    <PMID>19131375</PMID>
  </reference>
  <reference>
    <citation>Veith FJ, Lachat M, Mayer D, Malina M, Holst J, Mehta M, Verhoeven EL, Larzon T, Gennai S, Coppi G, Lipsitz EC, Gargiulo NJ, van der Vliet JA, Blankensteijn J, Buth J, Lee WA, Biasi G, Deleo G, Kasirajan K, Moore R, Soong CV, Cayne NS, Farber MA, Raithel D, Greenberg RK, van Sambeek MR, Brunkwall JS, Rockman CB, Hinchliffe RJ; RAAA Investigators. Collected world and single center experience with endovascular treatment of ruptured abdominal aortic aneurysms. Ann Surg. 2009 Nov;250(5):818-24. doi: 10.1097/SLA.0b013e3181bdd7f5.</citation>
    <PMID>19809296</PMID>
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    <citation>Papazoglou K, Mallios A, Rafati F, Zambas N, Karkos C. Endovascular treatment of ruptured abdominal aortic aneurysms with the Endurant device. Ann Vasc Surg. 2013 Feb;27(2):162-7. doi: 10.1016/j.avsg.2012.04.013. Epub 2012 Sep 12.</citation>
    <PMID>22981014</PMID>
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    <citation>Donas KP, Torsello GB, Piccoli G, Pitoulias GA, Torsello GF, Bisdas T, Austermann M, Gasparini D. The PROTAGORAS study to evaluate the performance of the Endurant stent graft for patients with pararenal pathologic processes treated by the chimney/snorkel endovascular technique. J Vasc Surg. 2016 Jan;63(1):1-7. doi: 10.1016/j.jvs.2015.07.080. Epub 2015 Oct 23.</citation>
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    <citation>Mayer D, Aeschbacher S, Pfammatter T, Veith FJ, Norgren L, Magnuson A, Rancic Z, Lachat M, Horer T, Skoog P, Larzon T. Complete replacement of open repair for ruptured abdominal aortic aneurysms by endovascular aneurysm repair: a two-center 14-year experience. Ann Surg. 2012 Nov;256(5):688-95; discussion 695-6. doi: 10.1097/SLA.0b013e318271cebd. Erratum In: Ann Surg. 2013 Jul;258(1):191. Horer, T [added]; Skoog, P [added].</citation>
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    <citation>Chaikof EL, Blankensteijn JD, Harris PL, White GH, Zarins CK, Bernhard VM, Matsumura JS, May J, Veith FJ, Fillinger MF, Rutherford RB, Kent KC; Ad Hoc Committee for Standardized Reporting Practices in Vascular Surgery of The Society for Vascular Surgery/American Association for Vascular Surgery. Reporting standards for endovascular aortic aneurysm repair. J Vasc Surg. 2002 May;35(5):1048-60. doi: 10.1067/mva.2002.123763. No abstract available.</citation>
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    <citation>Vu KN, Kaitoukov Y, Morin-Roy F, Kauffmann C, Giroux MF, Therasse E, Soulez G, Tang A. Rupture signs on computed tomography, treatment, and outcome of abdominal aortic aneurysms. Insights Imaging. 2014 Jun;5(3):281-93. doi: 10.1007/s13244-014-0327-3. Epub 2014 May 1.</citation>
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  <results_reference>
    <citation>Anjum A, von Allmen R, Greenhalgh R, Powell JT. Explaining the decrease in mortality from abdominal aortic aneurysm rupture. Br J Surg. 2012 May;99(5):637-45. doi: 10.1002/bjs.8698.</citation>
    <PMID>22473277</PMID>
  </results_reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 5, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>August 25, 2021</last_update_submitted>
  <last_update_submitted_qc>August 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ippokrateio General Hospital of Thessaloniki</investigator_affiliation>
    <investigator_full_name>Kostantinos Papazoglou</investigator_full_name>
    <investigator_title>Professor in Vascular surgery</investigator_title>
  </responsible_party>
  <keyword>Ruptured Abdominal Aortic Aneurysm</keyword>
  <keyword>Endovascular Repair</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Aneurysm, Ruptured</mesh_term>
    <mesh_term>Aortic Aneurysm, Abdominal</mesh_term>
    <mesh_term>Aortic Rupture</mesh_term>
    <mesh_term>Rupture</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD data that underlie results in a publication will be released by the end of the study</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>By the end of the study, until publication</ipd_time_frame>
    <ipd_access_criteria>GDPR compatible</ipd_access_criteria>
  </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/NCT04471181
org study id: GRAND study
nct id: NCT04471181
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This will be a non-randomized, prospective, observational multi-center research study. Its
      purpose will be to assess the mortality and outcome of EVAR in patients with rAAA. As
      mentioned in the introduction, EVAR approach for ruptured bdominal aortic aneurysms is
      nowdays common clinical practice in many vascular centers , and the main treatment option in
      Hippokrateio General hospital. The same applies in all future participating vascular centers.
Ruptured abdominal aortic aneurysms (rAAAs) remain one of the most emergent medical events,
      with over 90% mortality if left untreated and a prevalence of a minimum 45 patients per
      1000000 population. The 30 day mortality for emergency open repair has remained at around
      50%, and there is no consistent improvement in the outcome of the open technique over time.
      Since its development, endovascular aneurysm repair (EVAR), has been increasingly used even
      in the emergency setting.

      So far there have been 4 randomized controlled trials, comparing EVAR versus open repair for
      rAAA. The first was a small trial from Nottingham followed by the Dutch trial AJAX and the
      French ECAR. The last and biggest trial with 613 patients was the UK IMPROVE trial. All these
      trials showed non inferiority of EVAR, but failed to prove benefit for EVAR with respect to
      30 day mortality. Furthermore two meta-analysisof the above RCTs, stated again, that 30 and
      90 day mortality is similar between EVAR and open surgery, with the exception of women having
      a better outcome with an endovascular approach.

      On the contrary, multiple observational studies and registries showed even a 50% risk
      reduction in mortality with EVAR. There has been huge critique and discussion of the results
      in IMPROVE trial, in which 10% of patients crossed over to the non-allocated treatment group.
      In both groups, patients who were treated with EVAR had a mortality of 25%, significantly
      lower than those who received open surgery (38%). Furthermore, two recent published studies
      that compared mortality of rAAA between Sweden, USA and UK, came to the conclusion that
      mortality is lower in centers that accept a large number of cases with rAAA, mostly treated
      with EVAR. There is an argument that these encouraging results are subject of bias, since
      there is patient selection according to haemodynamic stability and aortic morphology. A valid
      counter argument stated by Lachat and colleagues is that EVAR for rAAA in their center, in
      the moderate risk, stable patient with favourable anatomy (aortic neck length >10mm) has a
      reduced 30 day mortality of 10%, a result never demonstrated with open repair. As EVAR
      evolves, new technical features of the devices may address the current limitations of the
      technique. In addition, the anatomic suitability obstacle for EVAR has been revoked by the
      PROTAGORAS study, which led to CE mark for a commercial stent graft system, allowing
      treatment of aortic neck lengths as small as 2mm with the use of chimney technique. The
      authors in the IMPROVE trial acknowledge the fact that: "The suitability of ruptured aneurym
      for EVAR is subjective and will be defined by the aortic morphology, the experience of the
      operator and the range of resuscitation, endovascular and anaesthetic techniques available".

      It is safe to guess that haemodynamically compromised patients would benefit from a less
      invasive procedure, with minimum surgical exposure, if any, and local anaesthesia. There is
      no doubt however that for a center to adopt an EVAR only policy, poses many logistical
      challenges.

      The aim for this research study is that an "EVAR first" approach is feasible in rAAA, even in
      more complex anatomies and in patients with less physiologic reserve and at the same time
      prove that short and midterm mortality and morbidity with EVAR is significantly lower than
      open repair when compared to the mortality and morbidity rates of patients receiving open
      repair in the latest RCT "IMPROVE". This can be achieved, with implementing a treatment
      alogorithm for the pre intra and post operative time, based on already established protocols
      and relevant international standards, with single aim to avoid the factors in patient
      management that contribute to mortality and morbidity. Furthermore this research study will
      show increased applicability of EVAR in ruptured AAAs with shorter and larger in diameter
      proximal neck and with angulation >60 degrees, with the implementation of EndoAnchors
      (HeliFX). Another aim for this research study is to identify the role of the clotting
      mechanism in the overall mortality and thus to distinguish patient clotting profiles that can
      predict or alter the outcome.
observational model: Case-Only
time perspective: Prospective
measure: Mortality Rate
time frame: 30 days
description: Any cause mortality after EVAR
measure: Time from rupture to diagnosis
time frame: pre-intervention
description: In minutes
measure: Time from diagnosis to intervention
time frame: pre-intervention
description: In minutes
measure: Rate of procedures converted to open repair
time frame: 24 hours post-operatively
description: Any reason for conversion to open repair
measure: Total mortality rate
time frame: 12 months post-operatively
description: All cause mortality
measure: Rate of Major Adverse Events (MAE)
time frame: 30 days, 3 months and 12 months
description: MAE include :bowel ischaemia, myocardial infraction, paraplegia, renal failure, stroke, abdominal compartment syndrome, lower limb ischeamia
measure: Rate of Endoleaks
time frame: immediately after the procedure, 3 months after the procedure, 12 months after the procedure
description: Any endoleak observed
measure: Rate of Graft related complications
time frame: 12 months after the procedure
description: Any graft related complication
measure: Fibrinogel levels
time frame: Pre-intervention, 24 hours after the procedure, 3 months after the procedure,12 months after the procedure
description: Fibrinogen levels mg/dL
arm group label: All patients with ruptured abdominal aortic aneurysms
description: All patients will undergo CTA to confirm the diagnosis. The use of balloon for aortic clamp in case of haemodynamic instability can be used.
All patients included in the research study must undergo standard EVAR with a bifurcated graft or an aorto-uni-iliac and a femoral to femoral crossover. In aneurysms with short proximal neck down to 4mm, or in cases where completion angiography indicates type Ia endoleak, the Heli-FX EndoAnchor system is recommended to be used, as indicated. All patients will have plain abdominal x-rays on discharge. Participants will undergo CTA in 3months and annually post-op.. In case of an adverse event before the 3 months follow up CTA, a more urgent imaging might be requested and proceed to appropriate action according to the findings.
intervention type: Device
intervention name: Endovascular repair of ruptured abdominal aortic aneurysm (EVAR) with Medtronic Endurant
description: Endovascular repair (EVAR) of ruptured abdominal aortic aneurysms with Medtronic Endurant II, and IIs device
arm group label: All patients with ruptured abdominal aortic aneurysms
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Kostantinos Papazoglou, Professor
role: Principal Investigator
affiliation: Aristotle University Of Thessaloniki
last name: Kostantinos Papazoglou, Professor
phone: 00306944582211
email: kpapas@auth.gr
last name: Ioakeim Giagtzidis, Consultant
phone: 00306979666129
email: kimisnet@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Greece
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PMID: 24418950
citation: Hinchliffe RJ, Bruijstens L, MacSweeney ST, Braithwaite BD. A randomised trial of endovascular and open surgery for ruptured abdominal aortic aneurysm - results of a pilot study and lessons learned for future studies. Eur J Vasc Endovasc Surg. 2006 Nov;32(5):506-13; discussion 514-5. doi: 10.1016/j.ejvs.2006.05.016. Epub 2006 Aug 1.
PMID: 16887369
citation: Reimerink JJ, Hoornweg LL, Vahl AC, Wisselink W, van den Broek TA, Legemate DA, Reekers JA, Balm R; Amsterdam Acute Aneurysm Trial Collaborators. Endovascular repair versus open repair of ruptured abdominal aortic aneurysms: a multicenter randomized controlled trial. Ann Surg. 2013 Aug;258(2):248-56. doi: 10.1097/SLA.0b013e31828d4b76.
PMID: 23549424
citation: Desgranges P, Kobeiter H, Katsahian S, Bouffi M, Gouny P, Favre JP, Alsac JM, Sobocinski J, Julia P, Alimi Y, Steinmetz E, Haulon S, Alric P, Canaud L, Castier Y, Jean-Baptiste E, Hassen-Khodja R, Lermusiaux P, Feugier P, Destrieux-Garnier L, Charles-Nelson A, Marzelle J, Majewski M, Bourmaud A, Becquemin JP; ECAR Investigators. Editor's Choice - ECAR (Endovasculaire ou Chirurgie dans les Anevrysmes aorto-iliaques Rompus): A French Randomized Controlled Trial of Endovascular Versus Open Surgical Repair of Ruptured Aorto-iliac Aneurysms. Eur J Vasc Endovasc Surg. 2015 Sep;50(3):303-10. doi: 10.1016/j.ejvs.2015.03.028. Epub 2015 May 20.
PMID: 26001320
citation: van Beek SC, Conijn AP, Koelemay MJ, Balm R. Editor's Choice - Endovascular aneurysm repair versus open repair for patients with a ruptured abdominal aortic aneurysm: a systematic review and meta-analysis of short-term survival. Eur J Vasc Endovasc Surg. 2014 Jun;47(6):593-602. doi: 10.1016/j.ejvs.2014.03.003. Epub 2014 Apr 18.
PMID: 24746873
citation: Sweeting MJ, Balm R, Desgranges P, Ulug P, Powell JT; Ruptured Aneurysm Trialists. Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm. Br J Surg. 2015 Sep;102(10):1229-39. doi: 10.1002/bjs.9852. Epub 2015 Jun 24.
PMID: 26104471
citation: Karthikesalingam A, Holt PJ, Vidal-Diez A, Ozdemir BA, Poloniecki JD, Hinchliffe RJ, Thompson MM. Mortality from ruptured abdominal aortic aneurysms: clinical lessons from a comparison of outcomes in England and the USA. Lancet. 2014 Mar 15;383(9921):963-9. doi: 10.1016/S0140-6736(14)60109-4.
PMID: 24629298
citation: Karthikesalingam A, Wanhainen A, Holt PJ, Vidal-Diez A, Brownrigg JR, Shpitser I, Bjorck M, Thompson MM, Mani K. Comparison of long-term mortality after ruptured abdominal aortic aneurysm in England and Sweden. Br J Surg. 2016 Feb;103(3):199-206. doi: 10.1002/bjs.10049. Epub 2015 Dec 1.
PMID: 26620854
citation: Vogel TR, Dombrovskiy VY, Haser PB, Graham AM. Has the implementation of EVAR for ruptured AAA improved outcomes? Vasc Endovascular Surg. 2009 Jun-Jul;43(3):252-7. doi: 10.1177/1538574408329271. Epub 2009 Jan 8.
PMID: 19131375
citation: Veith FJ, Lachat M, Mayer D, Malina M, Holst J, Mehta M, Verhoeven EL, Larzon T, Gennai S, Coppi G, Lipsitz EC, Gargiulo NJ, van der Vliet JA, Blankensteijn J, Buth J, Lee WA, Biasi G, Deleo G, Kasirajan K, Moore R, Soong CV, Cayne NS, Farber MA, Raithel D, Greenberg RK, van Sambeek MR, Brunkwall JS, Rockman CB, Hinchliffe RJ; RAAA Investigators. Collected world and single center experience with endovascular treatment of ruptured abdominal aortic aneurysms. Ann Surg. 2009 Nov;250(5):818-24. doi: 10.1097/SLA.0b013e3181bdd7f5.
PMID: 19809296
citation: Papazoglou K, Mallios A, Rafati F, Zambas N, Karkos C. Endovascular treatment of ruptured abdominal aortic aneurysms with the Endurant device. Ann Vasc Surg. 2013 Feb;27(2):162-7. doi: 10.1016/j.avsg.2012.04.013. Epub 2012 Sep 12.
PMID: 22981014
citation: Donas KP, Torsello GB, Piccoli G, Pitoulias GA, Torsello GF, Bisdas T, Austermann M, Gasparini D. The PROTAGORAS study to evaluate the performance of the Endurant stent graft for patients with pararenal pathologic processes treated by the chimney/snorkel endovascular technique. J Vasc Surg. 2016 Jan;63(1):1-7. doi: 10.1016/j.jvs.2015.07.080. Epub 2015 Oct 23.
PMID: 26476671
citation: Mayer D, Aeschbacher S, Pfammatter T, Veith FJ, Norgren L, Magnuson A, Rancic Z, Lachat M, Horer T, Skoog P, Larzon T. Complete replacement of open repair for ruptured abdominal aortic aneurysms by endovascular aneurysm repair: a two-center 14-year experience. Ann Surg. 2012 Nov;256(5):688-95; discussion 695-6. doi: 10.1097/SLA.0b013e318271cebd. Erratum In: Ann Surg. 2013 Jul;258(1):191. Horer, T [added]; Skoog, P [added].
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citation: Chaikof EL, Blankensteijn JD, Harris PL, White GH, Zarins CK, Bernhard VM, Matsumura JS, May J, Veith FJ, Fillinger MF, Rutherford RB, Kent KC; Ad Hoc Committee for Standardized Reporting Practices in Vascular Surgery of The Society for Vascular Surgery/American Association for Vascular Surgery. Reporting standards for endovascular aortic aneurysm repair. J Vasc Surg. 2002 May;35(5):1048-60. doi: 10.1067/mva.2002.123763. No abstract available.
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citation: Vu KN, Kaitoukov Y, Morin-Roy F, Kauffmann C, Giroux MF, Therasse E, Soulez G, Tang A. Rupture signs on computed tomography, treatment, and outcome of abdominal aortic aneurysms. Insights Imaging. 2014 Jun;5(3):281-93. doi: 10.1007/s13244-014-0327-3. Epub 2014 May 1.
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citation: Mell MW, Starnes BW, Kraiss LW, Schneider PA, Pevec WC. Western Vascular Society guidelines for transfer of patients with ruptured abdominal aortic aneurysm. J Vasc Surg. 2017 Mar;65(3):603-608. doi: 10.1016/j.jvs.2016.10.097.
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citation: Anjum A, von Allmen R, Greenhalgh R, Powell JT. Explaining the decrease in mortality from abdominal aortic aneurysm rupture. Br J Surg. 2012 May;99(5):637-45. doi: 10.1002/bjs.8698.
PMID: 22473277
responsible party type: Sponsor-Investigator
investigator affiliation: Ippokrateio General Hospital of Thessaloniki
investigator full name: Kostantinos Papazoglou
investigator title: Professor in Vascular surgery
mesh term: Aneurysm
mesh term: Aneurysm, Ruptured
mesh term: Aortic Aneurysm, Abdominal
mesh term: Aortic Rupture
mesh term: Rupture
sharing ipd: Yes
ipd description: All IPD data that underlie results in a publication will be released by the end of the study
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: By the end of the study, until publication
ipd access criteria: GDPR compatible