<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/NCT03763812</url>
  </required_header>
  <id_info>
    <org_study_id>INSPIRE study</org_study_id>
    <nct_id>NCT03763812</nct_id>
  </id_info>
  <brief_title>Post Implant Syndrome After EVAR and EVAS (INSPIRE Study)</brief_title>
  <official_title>Explorative Study on the Inflammatory Response After Endovascular Aortic Aneurysm Repair and Endovascular Aneurysm Sealing.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rijnstate Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rijnstate Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      Retrospective data have shown that active sac management, as applied in EVAS, reduces the&#xD;
      incidence of the post-implant syndrome. All-cause and cardiac mortality at one-year seems to&#xD;
      be lower after EVAS when compared to EVAR. Ongoing, low grade, inflammation could differ&#xD;
      between techniques and induce cardiac damage.&#xD;
&#xD;
      This study is designed to establish whether EVAS results in a reduced post-operative&#xD;
      inflammatory response during the first year after surgery, compared to EVAR as assessed by&#xD;
      trends in circulating inflammatory cytokine concentration.&#xD;
&#xD;
      Study design: International prospective, comparative, explorative study. Study population:&#xD;
      Patients scheduled to undergo infra-renal EVAR with a polyester endograft or EVAS for an&#xD;
      infrarenal aortic aneurysm. This is an explorative study and therefore only patients who&#xD;
      would normally receive a suitable device as part of standard treatment at the participating&#xD;
      institutes will be recruited. Blood samples will be taken at specified time points before and&#xD;
      after surgery.&#xD;
&#xD;
      Main study parameters/endpoints: The difference in early post-operative and long term&#xD;
      inflammatory response between EVAS and EVAR, measured by the incidence of the post-implant&#xD;
      syndrome. To investigate the incidence of the post-implant syndrome, the rise in CRP, WBC and&#xD;
      circulating cytokines, at specified time points up to 12 months after surgery and the change&#xD;
      in aortic thrombus volume and its relationship with the inflammatory response, measured by&#xD;
      cytokines' concentrations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Endovascular sealing of abdominal aortic aneurysms (EVAS) is a new technique to treat&#xD;
      infrarenal abdominal aortic aneurysms (AAA), which can be performed more expeditiously than&#xD;
      endovascular aneurysm repair (EVAR). The difference with EVAR is that fixation and seal are&#xD;
      provided from polymer filled endobags that are placed in the aneurysmal sac. The&#xD;
      post-implantation syndrome (PIS) is the clinical and biochemical expression of an&#xD;
      inflammatory response following endovascular repair of an aortic aneurysm. More specifically,&#xD;
      the presence of fever (body temperature &gt;38 C for ≥1 day) and leukocytosis (white blood cell&#xD;
      count (WBC) &gt;12.000/mL) with negative blood cultures and is occurring in over 30% cases after&#xD;
      EVAR. It is related to prolonged hospital stay and elevated CRP levels, that in turn increase&#xD;
      the risk on major adverse cardiac events. The literature showed that the magnitude of the&#xD;
      post-operative inflammatory response depends on the type of endoprothesis used for EVAR and&#xD;
      that EVAS is related to a lower post-operative CRP level, lower white blood counts, a lower&#xD;
      temperature and less cardiac complications compared to standard EVAR.&#xD;
&#xD;
      The current study was designed to explore the occurence of the post-implant syndrome after&#xD;
      EVAR and EVAS. This study was also designed to unravel the cytokines which are involved in&#xD;
      the post-implant syndrome after EVAR and EVAS.&#xD;
&#xD;
      In this international, prospective, explorative study 60 patients who are scheduled for EVAR&#xD;
      and 60 patients who are scheduled for EVAS will be included. Blood samples (for WBC and&#xD;
      circulating cytokines (TNF-α, Interleukin (IL)-1, 1RA, 6, 10, 18, CRP), Troponin T, HsTnT,&#xD;
      NT-pro-BNP)) will be taken at:&#xD;
&#xD;
        -  Before induction of anesthesia&#xD;
&#xD;
        -  At wound closure&#xD;
&#xD;
        -  24 hours after surgery&#xD;
&#xD;
        -  48 hours after surgery&#xD;
&#xD;
        -  1 month after surgery&#xD;
&#xD;
        -  6 months after surgery&#xD;
&#xD;
        -  12 months after surgery&#xD;
&#xD;
      Patients are finished with the study after 12 months of follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Nellix stent cannot be placed in patients yet.&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>No masking since patients, doctor and researchers know if patients undergo EVAR or EVAS.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in inflammatory response between EVAS and EVAR</measure>
    <time_frame>Up to 12 months after surgery.</time_frame>
    <description>The change in early post-operative inflammatory response between EVAS and EVAR, measured by the incidence of the post-implant syndrome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in inflammatory response between EVAS and EVAR</measure>
    <time_frame>Up to 12 months after surgery.</time_frame>
    <description>The change in long term inflammatory response between EVAS and EVAR, measured by the incidence of the post-implant syndrome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in aortic thrombus volume</measure>
    <time_frame>Up to 12 months after surgery.</time_frame>
    <description>The change in aortic thrombus volume and its relationship with the inflammatory response, measured by cytokines' concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pyrexia post operative</measure>
    <time_frame>24 to 48 hours after surgery</time_frame>
    <description>Post-operative pyrexia, measured at 24 and 48 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day Morbidity</measure>
    <time_frame>Up to 30 days after surgery</time_frame>
    <description>30-day morbidity measured by cytokines' concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1 year morbidity</measure>
    <time_frame>Up to 12 months after surgery.</time_frame>
    <description>1 year morbidity measured by cytokines' concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac complications</measure>
    <time_frame>Up to 12 months after surgery.</time_frame>
    <description>Cardiac complications (including measures of Troponin T, hsTnT, NT-proBNP) measured by cytokines' concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Up to 12 months after surgery.</time_frame>
    <description>(all-cause and cardiac) mortality measured by cytokines' concentrations.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Abdominal Aortic Aneurysm</condition>
  <condition>Inflammatory Response</condition>
  <arm_group>
    <arm_group_label>Endovascular Aneurysm Repair (EVAR)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients scheduled for EVAR will be included and blood samples at 7 time points will be taken.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Endovascular Aneurysm Sealing (EVAS)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients scheduled for EVAS will be included and blood samples at 7 time points will be taken.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endovascular Aneurysm Repair (EVAR)</intervention_name>
    <description>The following blood samples will be taken: WBC and circulating cytokines (TNF-α, Interleukin (IL)-1, 1RA, 6, 10, 18, CRP), Troponin T, HsTnT, NT-pro-BNP at these time points:&#xD;
Before induction of anesthesia&#xD;
At wound closure&#xD;
24 hours after surgery&#xD;
48 hours after surgery&#xD;
1 month after surgery&#xD;
6 months after surgery&#xD;
12 months after surgery</description>
    <arm_group_label>Endovascular Aneurysm Repair (EVAR)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endovascular Aneurysm Sealing (EVAS)</intervention_name>
    <description>The following blood samples will be taken: WBC and circulating cytokines (TNF-α, Interleukin (IL)-1, 1RA, 6, 10, 18, CRP), Troponin T, HsTnT, NT-pro-BNP at these time points:&#xD;
Before induction of anesthesia&#xD;
At wound closure&#xD;
24 hours after surgery&#xD;
48 hours after surgery&#xD;
1 month after surgery&#xD;
6 months after surgery&#xD;
12 months after surgery</description>
    <arm_group_label>Endovascular Aneurysm Sealing (EVAS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Elective EVAR/EVAS&#xD;
&#xD;
          -  Ability and willingness to provide written informed consent&#xD;
&#xD;
          -  Age &gt;50 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Complex EVAR or EVAS, including iliac branched and supra-renal repairs (pre-planned&#xD;
             visceral chimneys, fenestrations or branches)&#xD;
&#xD;
          -  Ruptured or symptomatic AAA&#xD;
&#xD;
          -  Planned internal iliac artery embolization&#xD;
&#xD;
          -  Acute or chronic inflammatory illness (i.e. upper respiratory tract infection)&#xD;
&#xD;
          -  Active rheumatoid arthritis&#xD;
&#xD;
          -  Inflammatory bowel disease, etc.)&#xD;
&#xD;
          -  Inflammatory and mycotic aneurysms&#xD;
&#xD;
          -  Planned associated surgical procedure (i.e. iliac conduit, femoral endarterectomy,&#xD;
             etc.)&#xD;
&#xD;
          -  Previous aortic surgery (open or endovascular)&#xD;
&#xD;
          -  Untreated malignancy&#xD;
&#xD;
          -  Major surgery six weeks before EVAR/EVAS&#xD;
&#xD;
          -  Ongoing or recent immunosuppressive treatment, including corticosteroid use&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michel Reijnen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rijnstate Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Marienhospital Kevelaer</name>
      <address>
        <city>Kevelaer</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rijnstate</name>
      <address>
        <city>Arnhem</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital No.1</name>
      <address>
        <city>Bydgoszcz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Wojewódzki nr 4</name>
      <address>
        <city>Bytom</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institution Hematologii I Transfuzjologii,</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari I Politècnic La Fe</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>March 27, 2019</last_update_submitted>
  <last_update_submitted_qc>March 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rijnstate Hospital</investigator_affiliation>
    <investigator_full_name>Michel Reijnen</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>EVAR</keyword>
  <keyword>EVAS</keyword>
  <keyword>Post implant syndrome</keyword>
  <keyword>Abdominal Aortic Aneurysm</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, Abdominal</mesh_term>
  </condition_browse>
  <!-- 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/NCT03763812
org study id: INSPIRE study
nct id: NCT03763812
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Retrospective data have shown that active sac management, as applied in EVAS, reduces the
      incidence of the post-implant syndrome. All-cause and cardiac mortality at one-year seems to
      be lower after EVAS when compared to EVAR. Ongoing, low grade, inflammation could differ
      between techniques and induce cardiac damage.

      This study is designed to establish whether EVAS results in a reduced post-operative
      inflammatory response during the first year after surgery, compared to EVAR as assessed by
      trends in circulating inflammatory cytokine concentration.

      Study design: International prospective, comparative, explorative study. Study population:
      Patients scheduled to undergo infra-renal EVAR with a polyester endograft or EVAS for an
      infrarenal aortic aneurysm. This is an explorative study and therefore only patients who
      would normally receive a suitable device as part of standard treatment at the participating
      institutes will be recruited. Blood samples will be taken at specified time points before and
      after surgery.

      Main study parameters/endpoints: The difference in early post-operative and long term
      inflammatory response between EVAS and EVAR, measured by the incidence of the post-implant
      syndrome. To investigate the incidence of the post-implant syndrome, the rise in CRP, WBC and
      circulating cytokines, at specified time points up to 12 months after surgery and the change
      in aortic thrombus volume and its relationship with the inflammatory response, measured by
      cytokines' concentrations.
Endovascular sealing of abdominal aortic aneurysms (EVAS) is a new technique to treat
      infrarenal abdominal aortic aneurysms (AAA), which can be performed more expeditiously than
      endovascular aneurysm repair (EVAR). The difference with EVAR is that fixation and seal are
      provided from polymer filled endobags that are placed in the aneurysmal sac. The
      post-implantation syndrome (PIS) is the clinical and biochemical expression of an
      inflammatory response following endovascular repair of an aortic aneurysm. More specifically,
      the presence of fever (body temperature >38 C for ≥1 day) and leukocytosis (white blood cell
      count (WBC) >12.000/mL) with negative blood cultures and is occurring in over 30% cases after
      EVAR. It is related to prolonged hospital stay and elevated CRP levels, that in turn increase
      the risk on major adverse cardiac events. The literature showed that the magnitude of the
      post-operative inflammatory response depends on the type of endoprothesis used for EVAR and
      that EVAS is related to a lower post-operative CRP level, lower white blood counts, a lower
      temperature and less cardiac complications compared to standard EVAR.

      The current study was designed to explore the occurence of the post-implant syndrome after
      EVAR and EVAS. This study was also designed to unravel the cytokines which are involved in
      the post-implant syndrome after EVAR and EVAS.

      In this international, prospective, explorative study 60 patients who are scheduled for EVAR
      and 60 patients who are scheduled for EVAS will be included. Blood samples (for WBC and
      circulating cytokines (TNF-α, Interleukin (IL)-1, 1RA, 6, 10, 18, CRP), Troponin T, HsTnT,
      NT-pro-BNP)) will be taken at:

        -  Before induction of anesthesia

        -  At wound closure

        -  24 hours after surgery

        -  48 hours after surgery

        -  1 month after surgery

        -  6 months after surgery

        -  12 months after surgery

      Patients are finished with the study after 12 months of follow-up.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
masking description: No masking since patients, doctor and researchers know if patients undergo EVAR or EVAS.
measure: Change in inflammatory response between EVAS and EVAR
time frame: Up to 12 months after surgery.
description: The change in early post-operative inflammatory response between EVAS and EVAR, measured by the incidence of the post-implant syndrome.
measure: Change in inflammatory response between EVAS and EVAR
time frame: Up to 12 months after surgery.
description: The change in long term inflammatory response between EVAS and EVAR, measured by the incidence of the post-implant syndrome.
measure: Change in aortic thrombus volume
time frame: Up to 12 months after surgery.
description: The change in aortic thrombus volume and its relationship with the inflammatory response, measured by cytokines' concentrations.
measure: Pyrexia post operative
time frame: 24 to 48 hours after surgery
description: Post-operative pyrexia, measured at 24 and 48 hours.
measure: 30-day Morbidity
time frame: Up to 30 days after surgery
description: 30-day morbidity measured by cytokines' concentrations.
measure: 1 year morbidity
time frame: Up to 12 months after surgery.
description: 1 year morbidity measured by cytokines' concentrations.
measure: Cardiac complications
time frame: Up to 12 months after surgery.
description: Cardiac complications (including measures of Troponin T, hsTnT, NT-proBNP) measured by cytokines' concentrations.
measure: Mortality
time frame: Up to 12 months after surgery.
description: (all-cause and cardiac) mortality measured by cytokines' concentrations.
arm group label: Endovascular Aneurysm Repair (EVAR)
arm group type: Other
description: Patients scheduled for EVAR will be included and blood samples at 7 time points will be taken.
arm group label: Endovascular Aneurysm Sealing (EVAS)
arm group type: Other
description: Patients scheduled for EVAS will be included and blood samples at 7 time points will be taken.
intervention type: Procedure
intervention name: Endovascular Aneurysm Repair (EVAR)
description: The following blood samples will be taken: WBC and circulating cytokines (TNF-α, Interleukin (IL)-1, 1RA, 6, 10, 18, CRP), Troponin T, HsTnT, NT-pro-BNP at these time points:
Before induction of anesthesia
At wound closure
24 hours after surgery
48 hours after surgery
1 month after surgery
6 months after surgery
12 months after surgery
arm group label: Endovascular Aneurysm Repair (EVAR)
intervention type: Procedure
intervention name: Endovascular Aneurysm Sealing (EVAS)
description: The following blood samples will be taken: WBC and circulating cytokines (TNF-α, Interleukin (IL)-1, 1RA, 6, 10, 18, CRP), Troponin T, HsTnT, NT-pro-BNP at these time points:
Before induction of anesthesia
At wound closure
24 hours after surgery
48 hours after surgery
1 month after surgery
6 months after surgery
12 months after surgery
arm group label: Endovascular Aneurysm Sealing (EVAS)
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Michel Reijnen
role: Principal Investigator
affiliation: Rijnstate Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Netherlands
country: New Zealand
country: Poland
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Rijnstate Hospital
investigator full name: Michel Reijnen
investigator title: Principal investigator
mesh term: Aneurysm
mesh term: Aortic Aneurysm
mesh term: Aortic Aneurysm, Abdominal