<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/NCT03835598</url>
  </required_header>
  <id_info>
    <org_study_id>NL68980.068.19</org_study_id>
    <nct_id>NCT03835598</nct_id>
  </id_info>
  <brief_title>Post-Operative Thrombocytopenia After Bio-prosthesis Implantation</brief_title>
  <acronym>PORTRAIT</acronym>
  <official_title>Post-Operative Thrombocytopenia After Bio-prosthesis Implantation (PORTRAIT Study): a Retrospective International Multicenter Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</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>
      The objective of the study is to obtain the clinical data from patients who received a&#xD;
      biological prosthesis in aortic or mitral position, in order to evaluate the occurrence of&#xD;
      peri-operative thrombocytopenia.&#xD;
&#xD;
      The aim of the study is to analyze the eventual clinical impact of the phenomenon&#xD;
      (re-operation for bleeding, blood transfusion) and the mortality rate.&#xD;
&#xD;
      This is a multicentre retrospective, observentional clinical study. This study will enroll up&#xD;
      to 5000 patients since 2000 to date.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiac surgery is commonly associated with a transient post-operative decrease in the&#xD;
      platelet count. Thrombocytopenia after cardiopulmonary bypass can be explained by&#xD;
      hemodilution, exposure to artificial surfaces with platelet activation and adhesion,&#xD;
      hypothermia, blood loss and mechanical sequestration. It usually occurs between the second&#xD;
      and third postoperative days, resulting in a reduction of platelet counts by 40-50% from&#xD;
      baseline values. Moreover, when a foreign body as a valve prosthesis is literally placed into&#xD;
      the blood flow, blood cells are constantly exposed to its surface and eventually inflammatory&#xD;
      and, perhaps, autoimmune reactions could start. The interactions biomaterial-blood induce&#xD;
      changes in platelet shape, metabolism as well as receptor-mediated dysfunction and lysis.&#xD;
      Then, any significant decline in the circulating platelet count raises concerns about&#xD;
      coagulation disorders and bleeding.&#xD;
&#xD;
      Despite the advanced hemodynamic performance, recently thrombocytopenia (defined as nadir&#xD;
      platelet count &lt; 150.000 x 1000/uL) has been associated to new aortic biological prostheses,&#xD;
      either rapid deployment or trans-catheter valves. Although several studies have been carried&#xD;
      on, the drop in the platelet count after aortic valve replacement with certain tissue valves&#xD;
      remains unexplained yet. The decrease after the valve implantation, however, is not&#xD;
      exclusively limited to the surgical prostheses. Trans-catheter aortic valves, in fact, were&#xD;
      found to be associated to post-procedure thrombocytopenia. Thrombocytopenia following&#xD;
      transcatheter aortic valve implantation (TAVI) procedures is related to the increased adverse&#xD;
      events rate such as death, stroke, acute kidney injury, bleeding and vascular complications.&#xD;
      Furthermore, thrombocytopenia seems to occur most likely associated after balloon-expandable&#xD;
      valves implantation.The literature, however, is confounding.&#xD;
&#xD;
      Despite several studies, little is known about the mechanism involved. Variations in&#xD;
      biocompatibility of valve tissue as like a strong immune/inflammatory response could be some&#xD;
      explanations. However, there is still uncertainty about the mechanism conditioning&#xD;
      post-operative platelet drop. To address this uncertain the underlying process should be&#xD;
      evaluated in a large multicentre trial.&#xD;
&#xD;
      The aims of the study are the following:&#xD;
&#xD;
        -  to analyze the occurrence of thrombocytopenia after isolated aortic valve&#xD;
           replacement/implantation and after isolated mitral valve replacement;&#xD;
&#xD;
        -  to evaluate the clinical impact of thrombocytopenia (length of stay, bleeding,&#xD;
           re-operation for bleeding, blood transfusion, mortality).&#xD;
&#xD;
      The study is multicentre, retrospective, observational and will enroll up to 5000 since 2000&#xD;
      to date.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 28, 2019</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 30, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Platelet count</measure>
    <time_frame>During the index hospital stay, an average of 5 days</time_frame>
    <description>to evaluate the rate of thrombocytopenia in patients receiving biological prosthesis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Platelet count</measure>
    <time_frame>1-3months follow-up</time_frame>
    <description>to evaluate the rate of thrombocytopenia in patients receiving biological prosthesis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>packed Red Cells transfusion, fresh frozen plasma transfusion, Platelet transfusion</measure>
    <time_frame>During the index hospital stay, an average of 5 days</time_frame>
    <description>to determine the low platelets-related complication rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Major bleeding (requiring more than 2 Red blood cells transfusions)</measure>
    <time_frame>From the index procedure up to 3 months</time_frame>
    <description>to determine the low platelets-related complication rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Re-exploration for bleeding</measure>
    <time_frame>From the index procedure up to 3 months</time_frame>
    <description>to determine the low platelets-related complication rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>Participants are followed during the duration of hospital stay (expected: up to 7 days post-op)</time_frame>
    <description>to assess the in-hospital mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital length of stay</measure>
    <time_frame>From the index procedure through discharge from the hospital (expected: up to 7 days post-op)</time_frame>
    <description>Days after the prosthesis implantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>From the index procedure through discharge from the Intensive Care Unit (expected: up to 2 days post op)</time_frame>
    <description>Days after the prosthesis implantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastro-intestinal bleeding</measure>
    <time_frame>From the index procedure within 3 months</time_frame>
    <description>Occurrence of gastro-intestinal bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial Bleeding</measure>
    <time_frame>From the index procedure within 3 months</time_frame>
    <description>Occurrence of intra-cranial bleeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombosis</measure>
    <time_frame>From the index procedure within 3 months</time_frame>
    <description>Occurrence of Thrombosis (arterial or venous)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day mortality</measure>
    <time_frame>within 30 days</time_frame>
    <description>Mortality within 30 days</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1233</enrollment>
  <condition>Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>Patients with cardiac biological prosthesis</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The population is composed by adult patients submitted to isolated aortic valve&#xD;
        replacement, percutaneous trans-catheter aortic valve implantation, and mitral valve&#xD;
        replacement with a bio-prosthesis.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing isolated aortic valve replacement/implantation or isolated mitral&#xD;
             valve replacement with a biological prosthesis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existent thrombocytopenia;&#xD;
&#xD;
          -  Oncologic diseases;&#xD;
&#xD;
          -  Pre-existent infections/inflammations;&#xD;
&#xD;
          -  Use of drugs inducing thrombocytopenia (&lt;3months);&#xD;
&#xD;
          -  Combined cardiac surgery operations;&#xD;
&#xD;
          -  Recent percutaneous cardiac intervention (&lt;1month).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Federica Jiritano</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Yerebakan C, Kaminski A, Westphal B, Kundt G, Ugurlucan M, Steinhoff G, Liebold A. Thrombocytopenia after aortic valve replacement with the Freedom Solo stentless bioprosthesis. Interact Cardiovasc Thorac Surg. 2008 Aug;7(4):616-20. doi: 10.1510/icvts.2007.169326. Epub 2008 May 27.</citation>
    <PMID>18505752</PMID>
  </reference>
  <reference>
    <citation>Reents W, Babin-Ebell J, Zacher M, Diegeler A. Thrombocytopenia after aortic valve replacement with the Sorin Freedom Solo prosthesis. J Heart Valve Dis. 2011 May;20(3):313-8.</citation>
    <PMID>21714423</PMID>
  </reference>
  <reference>
    <citation>Repossini A, Tononi L, Martinil G, Di Bacco L, Girolettiz L, Rosati F, Muneretto C. Platelet activation after sorin freedom solo valve implantation: a comparative study with Carpentier-Edwards Perimount Magna. J Heart Valve Dis. 2014 Nov;23(6):777-82.</citation>
    <PMID>25790627</PMID>
  </reference>
  <reference>
    <citation>Albacker TB. Thrombocytopenia associated with Perceval sutureless aortic valve replacement in elderly patients: a word of caution. Heart Surg Forum. 2015 Jun 26;18(3):E093-7. doi: 10.1532/hsf.1324.</citation>
    <PMID>26115151</PMID>
  </reference>
  <reference>
    <citation>Stanger O, Grabherr M, Gahl B, Longnus S, Meinitzer A, Fiedler M, Tevaearai H, Carrel T. Thrombocytopaenia after aortic valve replacement with stented, stentless and sutureless bioprostheses. Eur J Cardiothorac Surg. 2017 Feb 1;51(2):340-346. doi: 10.1093/ejcts/ezw295. No abstract available.</citation>
    <PMID>28186236</PMID>
  </reference>
  <reference>
    <citation>Gallet R, Seemann A, Yamamoto M, Hayat D, Mouillet G, Monin JL, Gueret P, Couetil JP, Dubois-Rande JL, Teiger E, Lim P. Effect of transcatheter (via femoral artery) aortic valve implantation on the platelet count and its consequences. Am J Cardiol. 2013 Jun 1;111(11):1619-24. doi: 10.1016/j.amjcard.2013.01.332. Epub 2013 Mar 20.</citation>
    <PMID>23523059</PMID>
  </reference>
  <reference>
    <citation>Jilaihawi H, Doctor N, Chakravarty T, Kashif M, Mirocha J, Cheng W, Lill M, Nakamura M, Gheorghiu M, Makkar RR. Major thrombocytopenia after balloon-expandable transcatheter aortic valve replacement: prognostic implications and comparison to surgical aortic valve replacement. Catheter Cardiovasc Interv. 2015 Jan 1;85(1):130-7. doi: 10.1002/ccd.25430. Epub 2014 Feb 27.</citation>
    <PMID>24677617</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>September 3, 2021</last_update_submitted>
  <last_update_submitted_qc>September 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03835598
org study id: NL68980.068.19
nct id: NCT03835598
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of the study is to obtain the clinical data from patients who received a
      biological prosthesis in aortic or mitral position, in order to evaluate the occurrence of
      peri-operative thrombocytopenia.

      The aim of the study is to analyze the eventual clinical impact of the phenomenon
      (re-operation for bleeding, blood transfusion) and the mortality rate.

      This is a multicentre retrospective, observentional clinical study. This study will enroll up
      to 5000 patients since 2000 to date.
Cardiac surgery is commonly associated with a transient post-operative decrease in the
      platelet count. Thrombocytopenia after cardiopulmonary bypass can be explained by
      hemodilution, exposure to artificial surfaces with platelet activation and adhesion,
      hypothermia, blood loss and mechanical sequestration. It usually occurs between the second
      and third postoperative days, resulting in a reduction of platelet counts by 40-50% from
      baseline values. Moreover, when a foreign body as a valve prosthesis is literally placed into
      the blood flow, blood cells are constantly exposed to its surface and eventually inflammatory
      and, perhaps, autoimmune reactions could start. The interactions biomaterial-blood induce
      changes in platelet shape, metabolism as well as receptor-mediated dysfunction and lysis.
      Then, any significant decline in the circulating platelet count raises concerns about
      coagulation disorders and bleeding.

      Despite the advanced hemodynamic performance, recently thrombocytopenia (defined as nadir
      platelet count < 150.000 x 1000/uL) has been associated to new aortic biological prostheses,
      either rapid deployment or trans-catheter valves. Although several studies have been carried
      on, the drop in the platelet count after aortic valve replacement with certain tissue valves
      remains unexplained yet. The decrease after the valve implantation, however, is not
      exclusively limited to the surgical prostheses. Trans-catheter aortic valves, in fact, were
      found to be associated to post-procedure thrombocytopenia. Thrombocytopenia following
      transcatheter aortic valve implantation (TAVI) procedures is related to the increased adverse
      events rate such as death, stroke, acute kidney injury, bleeding and vascular complications.
      Furthermore, thrombocytopenia seems to occur most likely associated after balloon-expandable
      valves implantation.The literature, however, is confounding.

      Despite several studies, little is known about the mechanism involved. Variations in
      biocompatibility of valve tissue as like a strong immune/inflammatory response could be some
      explanations. However, there is still uncertainty about the mechanism conditioning
      post-operative platelet drop. To address this uncertain the underlying process should be
      evaluated in a large multicentre trial.

      The aims of the study are the following:

        -  to analyze the occurrence of thrombocytopenia after isolated aortic valve
           replacement/implantation and after isolated mitral valve replacement;

        -  to evaluate the clinical impact of thrombocytopenia (length of stay, bleeding,
           re-operation for bleeding, blood transfusion, mortality).

      The study is multicentre, retrospective, observational and will enroll up to 5000 since 2000
      to date.
observational model: Cohort
time perspective: Retrospective
measure: Platelet count
time frame: During the index hospital stay, an average of 5 days
description: to evaluate the rate of thrombocytopenia in patients receiving biological prosthesis
measure: Platelet count
time frame: 1-3months follow-up
description: to evaluate the rate of thrombocytopenia in patients receiving biological prosthesis
measure: packed Red Cells transfusion, fresh frozen plasma transfusion, Platelet transfusion
time frame: During the index hospital stay, an average of 5 days
description: to determine the low platelets-related complication rate
measure: Major bleeding (requiring more than 2 Red blood cells transfusions)
time frame: From the index procedure up to 3 months
description: to determine the low platelets-related complication rate
measure: Re-exploration for bleeding
time frame: From the index procedure up to 3 months
description: to determine the low platelets-related complication rate
measure: In-hospital mortality
time frame: Participants are followed during the duration of hospital stay (expected: up to 7 days post-op)
description: to assess the in-hospital mortality
measure: In-hospital length of stay
time frame: From the index procedure through discharge from the hospital (expected: up to 7 days post-op)
description: Days after the prosthesis implantation
measure: ICU length of stay
time frame: From the index procedure through discharge from the Intensive Care Unit (expected: up to 2 days post op)
description: Days after the prosthesis implantation
measure: Gastro-intestinal bleeding
time frame: From the index procedure within 3 months
description: Occurrence of gastro-intestinal bleeding
measure: Intracranial Bleeding
time frame: From the index procedure within 3 months
description: Occurrence of intra-cranial bleeding
measure: Thrombosis
time frame: From the index procedure within 3 months
description: Occurrence of Thrombosis (arterial or venous)
measure: 30-day mortality
time frame: within 30 days
description: Mortality within 30 days
arm group label: Patients with cardiac biological prosthesis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
facility: 
country: Netherlands
citation: Yerebakan C, Kaminski A, Westphal B, Kundt G, Ugurlucan M, Steinhoff G, Liebold A. Thrombocytopenia after aortic valve replacement with the Freedom Solo stentless bioprosthesis. Interact Cardiovasc Thorac Surg. 2008 Aug;7(4):616-20. doi: 10.1510/icvts.2007.169326. Epub 2008 May 27.
PMID: 18505752
citation: Reents W, Babin-Ebell J, Zacher M, Diegeler A. Thrombocytopenia after aortic valve replacement with the Sorin Freedom Solo prosthesis. J Heart Valve Dis. 2011 May;20(3):313-8.
PMID: 21714423
citation: Repossini A, Tononi L, Martinil G, Di Bacco L, Girolettiz L, Rosati F, Muneretto C. Platelet activation after sorin freedom solo valve implantation: a comparative study with Carpentier-Edwards Perimount Magna. J Heart Valve Dis. 2014 Nov;23(6):777-82.
PMID: 25790627
citation: Albacker TB. Thrombocytopenia associated with Perceval sutureless aortic valve replacement in elderly patients: a word of caution. Heart Surg Forum. 2015 Jun 26;18(3):E093-7. doi: 10.1532/hsf.1324.
PMID: 26115151
citation: Stanger O, Grabherr M, Gahl B, Longnus S, Meinitzer A, Fiedler M, Tevaearai H, Carrel T. Thrombocytopaenia after aortic valve replacement with stented, stentless and sutureless bioprostheses. Eur J Cardiothorac Surg. 2017 Feb 1;51(2):340-346. doi: 10.1093/ejcts/ezw295. No abstract available.
PMID: 28186236
citation: Gallet R, Seemann A, Yamamoto M, Hayat D, Mouillet G, Monin JL, Gueret P, Couetil JP, Dubois-Rande JL, Teiger E, Lim P. Effect of transcatheter (via femoral artery) aortic valve implantation on the platelet count and its consequences. Am J Cardiol. 2013 Jun 1;111(11):1619-24. doi: 10.1016/j.amjcard.2013.01.332. Epub 2013 Mar 20.
PMID: 23523059
citation: Jilaihawi H, Doctor N, Chakravarty T, Kashif M, Mirocha J, Cheng W, Lill M, Nakamura M, Gheorghiu M, Makkar RR. Major thrombocytopenia after balloon-expandable transcatheter aortic valve replacement: prognostic implications and comparison to surgical aortic valve replacement. Catheter Cardiovasc Interv. 2015 Jan 1;85(1):130-7. doi: 10.1002/ccd.25430. Epub 2014 Feb 27.
PMID: 24677617
responsible party type: Sponsor
mesh term: Thrombocytopenia
sharing ipd: Undecided