<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/NCT03288441</url>
  </required_header>
  <id_info>
    <org_study_id>METC 17-4-061</org_study_id>
    <nct_id>NCT03288441</nct_id>
  </id_info>
  <brief_title>Management and Outcomes of Anti-thrombotic Medication Use in Thrombocytopenia</brief_title>
  <acronym>MATTER</acronym>
  <official_title>Management Patterns of AntiThrombotics and Outcomes in Patients With Hematological Malignancy and ThrombocytopEnia: a Prospective Registry (MATTER 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>
      Background: Antithrombotic therapy in the context of treatment related thrombocytopenia (i.e.&#xD;
      low levels of platelets) is not uncommon. Guidelines are based upon a paucity of&#xD;
      retrospective data and focus on the scenario of cancer associated venous thrombosis and low&#xD;
      molecular weight heparin treatment. Even less is known regarding direct oral anticoagulants,&#xD;
      antiplatelet therapy, or anticoagulation prescribed for other indications.&#xD;
&#xD;
      Aims: The study aims are to evaluate how physicians manage anticoagulant and antiplatelet&#xD;
      medication in patients with hematological malignancy and thrombocytopenia, and to assess the&#xD;
      frequency of bleeding and thrombosis. Additional aims are to assess how management changes&#xD;
      affect drug activity and blood clotting (coagulation), and to evaluate the use of platelet&#xD;
      transfusions.&#xD;
&#xD;
      Design: The investigators plan a multinational prospective registry of patients admitted to&#xD;
      the inpatient hematology department or outpatient clinic at one of the study centers.&#xD;
      Patients with hematological malignancies, platelets below 50 X 109/L, and anticoagulant&#xD;
      and/or antiplatelet medication will be studied.&#xD;
&#xD;
      Patients will be enrolled when the combination of antiplatelet/anticoagulant medication and&#xD;
      thrombocytopenia is first detected. Patients will be followed until 30 days after the&#xD;
      baseline study visit (which occurs 30 days after enrollment or when platelets &lt; 50*109/L,&#xD;
      whichever come first) or death. Patients will be indexed at the time of baseline visit.&#xD;
&#xD;
      Patients will be excluded from study analysis if one of the following events occurs before&#xD;
      study index: Withdrawal of consent, death, clinically-relevant non-major bleeding or the&#xD;
      composite primary outcome.&#xD;
&#xD;
      Risk factors for bleeding and thrombosis will be recorded at baseline. Parameters from&#xD;
      routine blood tests will be recorded throughout the study. During the study major bleeding&#xD;
      events and thrombosis will be recorded. Investigational blood tests assessing coagulation and&#xD;
      drug activity will be drawn at baseline (=study index). Throughout the study all management&#xD;
      decisions regarding antithrombotic therapy, including platelet and red blood cell&#xD;
      transfusion, will be recorded. This is an observational study and management will be solely&#xD;
      at the discretion of the physician.&#xD;
&#xD;
      Analysis: The investigators will first look at the frequency of either bleeding or thrombosis&#xD;
      according to the type of management strategy and evaluate the platelet threshold at which a&#xD;
      given management strategy is employed.&#xD;
&#xD;
      At the next stage, in selected subgroups, the optimal management strategy with respect to&#xD;
      bleeding/thrombotic risk, will be determined.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Thrombocyte-level cohorts Patients will be divided into two groups based on the platelet&#xD;
           level at study index .&#xD;
&#xD;
             1. Thrombocytopenic Cohort: Patients with morning platelet count below 50*109/L at&#xD;
                study index. This is the main study cohort for all analyses&#xD;
&#xD;
             2. Non-thrombocytopenic Cohort: Patients whose morning platelet count is ≥ 50*109/L at&#xD;
                study index will be considered as a reference group, and not included in the&#xD;
                primary analysis.&#xD;
&#xD;
        -  Analysis of outcomes:&#xD;
&#xD;
      By definition, there will be an intervention at the time of study index (baseline), meaning&#xD;
      that even if no change is made, it will be considered an intervention. Each patient may have&#xD;
      multiple exposures/interventions over the study.&#xD;
&#xD;
      Therefore, in a time dependent analysis, each outcome will be linked to the&#xD;
      exposure/intervention at study index.&#xD;
&#xD;
      Each exposure/intervention will be linked with the platelet level on the day of the&#xD;
      intervention.&#xD;
&#xD;
      #Competing Events:&#xD;
&#xD;
      The following events (in addition to death) will be considered competing events and will be&#xD;
      considered as such in the statistical analyses of the outcomes:&#xD;
&#xD;
        1. The composite primary outcome&#xD;
&#xD;
        2. change in the antithrombotic regimen after study index&#xD;
&#xD;
        3. diagnosis of HIT or TTP&#xD;
&#xD;
        4. a change in the hematological malignancy treatment regimen. Study follow-up will&#xD;
           continue after these events, and study data will continue to be recorded until&#xD;
           censorship for end of study period or death.&#xD;
&#xD;
             -  Detecting selection bias:&#xD;
&#xD;
      Patients fulfilling the inclusion criteria but not included in the study, will be detected by&#xD;
      reviewing the medical records of the hematology institute, weekly. The baseline&#xD;
      characteristics and reason for not including these patients will be recorded retrospectively&#xD;
      in the &quot;not-included cohort&quot;. The baseline characteristics of this cohort will be compared&#xD;
      with the study cohort to ascertain whether selection bias exists.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 20, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>6 Months</target_duration>
  <primary_outcome>
    <measure>Composite of major bleeding or thrombosis</measure>
    <time_frame>30 days (from study index) or until death (whichever first)</time_frame>
    <description>1) ISTH-defined Major bleeding events defined as: Fatal bleeding; bleeding into a critical organ; clinically overt bleeding associated with a decrease in hemoglobin level of more than 2 g/dL or leading to the transfusion of two or more units of blood OR: 2) Thrombosis defined as: Any symptomatic deep or superficial venous or arterial thromboembolism demonstrated on objective imaging/laboratory tests. Ischemic strokes with no immediate imaging signs will also be considered events, provided this was diagnosed by a neurologist and that the patient had objective neurological signs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet transfusion related adverse effects</measure>
    <time_frame>30 days (from study index) or until death (whichever first)</time_frame>
    <description>Number of adverse effects (all types and individually grouped) related to platelet/plasma transfusion, occurring within 24 hours of transfusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically Relevant non-Major Bleeding</measure>
    <time_frame>30 days (from study index) or until death (whichever first)</time_frame>
    <description>Defined according to the ISTH criteria published in the journal of thrombosis and Hemostasis by Kaatz et al in 2015</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of platelet tranfusions</measure>
    <time_frame>30 days (from study index) or until death (whichever first)</time_frame>
    <description>Number of platelet transfusions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of RBC tranfusions</measure>
    <time_frame>30 days (from study index) or until death (whichever first)</time_frame>
    <description>Number of red blood cell transfusions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>30 days (from study index)</time_frame>
    <description>death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in antithrombotic management</measure>
    <time_frame>30 days (from study index) or until death (whichever first)</time_frame>
    <description>Change in dose/type of antiplatelet or anticoagulant medication OR change in platelet threshold, AFTER the initial intervention which was recorded at study index.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>peak anticoagulant intensity</measure>
    <time_frame>3 days after study index</time_frame>
    <description>anti-Xa, Hemoclot, INR, aPTT will be measured at peak, depending on the anticoagulant drug. Patients will be classified as having sub-therapeutic, therapeutic, supra-therapeutic treatment levels, based upon the reference range at the central laboratory. Only relevant for patients with anticoagulation undergoing dose change.</description>
  </other_outcome>
  <other_outcome>
    <measure>Whole blood coagulation</measure>
    <time_frame>3 days after study index</time_frame>
    <description>Measured by rotational thromboelastometry (ROTEM) drawn at study index</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Hematologic Neoplasms</condition>
  <condition>Thrombocytopenia</condition>
  <condition>Anticoagulants</condition>
  <condition>Platelet Aggregation Inhibitors</condition>
  <arm_group>
    <arm_group_label>antiplatelet only</arm_group_label>
    <description>Patients receiving antiplatelet medication, but not anticoagulation. Antiplatelet drugs include any class, dose or duration of any platelet aggregation inhibitor.&#xD;
This refers to the antithrombotic regimen when the current thrombocytopenia, or risk thereof (i.e. &quot;predicted&quot;), was first identified (even if the treatment is subsequently stopped)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>anticoagulant-based</arm_group_label>
    <description>Patients receiving only anticoagulants or both anticoagulant and antiplatelet medication combined. This includes any class, dose or duration of any antiplatelet or anticoagulant drug.&#xD;
This refers to the antithrombotic regimen when the current thrombocytopenia, or risk thereof (i.e. &quot;predicted&quot;), was first identified (even if the treatment is subsequently stopped)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hold</intervention_name>
    <description>Hold antithrombotic therapy</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
    <arm_group_label>antiplatelet only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prophylactic dose antithrombotic</intervention_name>
    <description>Reduction in antithrombotic medication dose to prophylactic dose (without changing type)</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Change antithrombotic Drug</intervention_name>
    <description>Change in type of antithrombotic therapy</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
    <arm_group_label>antiplatelet only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Change platelet transfusion threshold</intervention_name>
    <description>Increase or reduce platelet transfusion threshold</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
    <arm_group_label>antiplatelet only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Full dose antithrombotics</intervention_name>
    <description>Continue full dose antithrombotic therapy</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
    <arm_group_label>antiplatelet only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mechanical measures</intervention_name>
    <description>Mechanical measures to reduce thrombotic risk including: IVC filter insertion, Intermittent Pneumatic Compression (IPC), Removal of Central venous catheter</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermediate dose antithrombotic</intervention_name>
    <description>Reduction in antithrombotic medication dose to prophylactic dose (without changing type). Intermediate dose in between prophylactic and full dose</description>
    <arm_group_label>anticoagulant-based</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      After measuring the activity of anticoagulant drugs from the plasma when doses are modified,&#xD;
      remaining plasma will be retained for 5 years.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects treated at the inpatient or outpatient hematology departments at the participating&#xD;
        centers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any hematological malignancy with or without active treatment (including autologous or&#xD;
             allogeneic stem cell transplantation), irrespective of the treatment line and disease&#xD;
             status.&#xD;
&#xD;
          -  Disease-related and/or current/predicted treatment-related thrombocytopenia (&lt;50 X&#xD;
             109/L) of any duration.&#xD;
&#xD;
          -  Current antiplatelet and/or anticoagulant treatment of any duration and for any&#xD;
             indication. This treatment may have been started before or after diagnosis of the&#xD;
             hematological malignancy and thrombocytopenia.&#xD;
&#xD;
        &quot;Current&quot; refers to the time when the current thrombocytopenia, or risk thereof (i.e.&#xD;
        &quot;predicted&quot;), was first identified (even if the treatment is subsequently stopped)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous thrombocytopenia (&lt;50 X 109/L) while using the current antithrombotic&#xD;
             regimen.&#xD;
&#xD;
          -  Current diagnosis of heparin induced thrombocytopenia (HIT) or thrombotic&#xD;
             thrombocytopenia purpura (TTP)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Avi Leader, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rabin Medical Center, Petah Tikva, Israel</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hugo ten Cate, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Maastricht University Medical Center, Maastricht</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anna Falanga, MD</last_name>
    <role>Study Chair</role>
    <affiliation>A.O. Papa Giovanni XXIII - S.I.M.T.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Avi Leader, MD</last_name>
    <phone>+972-3-9377906</phone>
    <email>avileader@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hugo ten Cate, MD, PhD</last_name>
    <email>h.tencate@maastrichtuniversity.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University Hospital</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Rambam Health Care Campus</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yona Nadir, MD, PhD</last_name>
    </contact>
    <contact_backup>
      <last_name>Debbie Steiner, MHA</last_name>
      <phone>+972-4-8543592</phone>
      <email>d_steiner@rambam.health.gov.il</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Meir Medical Center</name>
      <address>
        <city>Kfar Saba</city>
        <zip>4428164</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Orly Avnery, MD</last_name>
      <phone>+972-9-7471755</phone>
      <email>avneryho@clalit.org.il</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petaẖ Tiqwa</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Galia Spectre, MD, PhD</last_name>
      <phone>+972-3-9377906</phone>
      <email>galiasp1@clalit.org.il</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ron Ram, MD</last_name>
      <phone>+972-3-697-3577</phone>
      <email>ronr@tlvmc.gov.il</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo di Alessandria</name>
      <address>
        <city>Alessandria</city>
        <zip>15121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Roberto Santi</last_name>
      <phone>+39 (0)131 206111</phone>
      <email>dr.rsanti@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>A.O. Papa Giovanni XXIII - S.I.M.T.</name>
      <address>
        <city>Bergamo</city>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Falanga, MD</last_name>
      <phone>+39-035.267.8597</phone>
      <email>annafalanga@icthic.com</email>
    </contact>
    <contact_backup>
      <last_name>Alessandro Rambaldi, MD</last_name>
      <email>arambaldi@asst-pg23.it</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>ASST degli Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Giuseppe Rossi</last_name>
      <phone>+39 (0)30 399 8870</phone>
      <email>giuseppe.rossi@asst-spedalicivili.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>A.O.U. di Modena</name>
      <address>
        <city>Modena</city>
        <zip>41125</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Marco Marietta</last_name>
      <phone>+39 (0)59 422 2111</phone>
      <email>marco.marietta1@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale San Gerardo di Monza</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Carrer</last_name>
      <email>mail.carrer@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital Policlinico di Palermo</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sergio Siragusa, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Mariasanta Napolitano</last_name>
      <phone>+39-91 655 1111</phone>
      <email>mariasanta.napolitano@unipa.it</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>A.O.U Policlinico Umberto I di Roma</name>
      <address>
        <city>Roma</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Antonio Chistolini</last_name>
      <phone>+39 06 49971</phone>
      <email>chistolini@bce.uniroma1.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario A. Gemelli</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Prof. Valerio De Stefano</last_name>
      <phone>+39 06 30151</phone>
      <email>valerio.destefano@unicatt.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Università degli studi di Roma &quot;Tor Vergata&quot;</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Ilaria Del Principe</last_name>
      <email>Del.Principe@Med.uniroma2.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>A.O.U. CITTA' della SALUTE e della SCIENZA di TORINO</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eloise Beggiato, MD</last_name>
      <phone>+39-11 633 1633</phone>
      <email>ebeggiato@cittadellasalute.to.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AZIENDA ULSS N. 8 BERICA di Vicenza</name>
      <address>
        <city>Vicenza</city>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr. Marco Ruggeri</last_name>
      <phone>+39 (0)444 753111</phone>
      <email>marco.ruggeri@ulssvicenza.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Amsterdam University Medical Centers</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Harry R Büller, MD, PhD</last_name>
      <email>h.r.buller@amc.uva.nl</email>
    </contact>
    <contact_backup>
      <last_name>Eva N Hamulyák, MD</last_name>
      <phone>+31 20 5667516</phone>
      <email>e.n.hamulyak@amc.uva.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karina Meijer, MD, PhD</last_name>
      <email>k.meijer@umcg.nl</email>
    </contact>
    <contact_backup>
      <last_name>Tessa Elling, MD</last_name>
      <phone>+31 6 31623491</phone>
      <email>t.elling@umcg.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Maastricht University Medical Center (MUMC+)</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Avi Leader, MD</last_name>
      <phone>+31-43-3874780</phone>
      <email>avileader@yahoo.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Erasmus Medical Center</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mandy Lauw, MD, PhD</last_name>
      <email>m.lauw@erasmusmc.nl</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HagaZiekenhuis</name>
      <address>
        <city>The Hague</city>
        <zip>2545 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location_countries>
    <country>Israel</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>September 16, 2020</last_update_submitted>
  <last_update_submitted_qc>September 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hematologic Neoplasms</keyword>
  <keyword>Thrombocytopenia</keyword>
  <keyword>Anticoagulants</keyword>
  <keyword>Platelet Aggregation Inhibitors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Thrombocytopenia</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/NCT03288441
org study id: METC 17-4-061
nct id: NCT03288441
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Antithrombotic therapy in the context of treatment related thrombocytopenia (i.e.
      low levels of platelets) is not uncommon. Guidelines are based upon a paucity of
      retrospective data and focus on the scenario of cancer associated venous thrombosis and low
      molecular weight heparin treatment. Even less is known regarding direct oral anticoagulants,
      antiplatelet therapy, or anticoagulation prescribed for other indications.

      Aims: The study aims are to evaluate how physicians manage anticoagulant and antiplatelet
      medication in patients with hematological malignancy and thrombocytopenia, and to assess the
      frequency of bleeding and thrombosis. Additional aims are to assess how management changes
      affect drug activity and blood clotting (coagulation), and to evaluate the use of platelet
      transfusions.

      Design: The investigators plan a multinational prospective registry of patients admitted to
      the inpatient hematology department or outpatient clinic at one of the study centers.
      Patients with hematological malignancies, platelets below 50 X 109/L, and anticoagulant
      and/or antiplatelet medication will be studied.

      Patients will be enrolled when the combination of antiplatelet/anticoagulant medication and
      thrombocytopenia is first detected. Patients will be followed until 30 days after the
      baseline study visit (which occurs 30 days after enrollment or when platelets < 50*109/L,
      whichever come first) or death. Patients will be indexed at the time of baseline visit.

      Patients will be excluded from study analysis if one of the following events occurs before
      study index: Withdrawal of consent, death, clinically-relevant non-major bleeding or the
      composite primary outcome.

      Risk factors for bleeding and thrombosis will be recorded at baseline. Parameters from
      routine blood tests will be recorded throughout the study. During the study major bleeding
      events and thrombosis will be recorded. Investigational blood tests assessing coagulation and
      drug activity will be drawn at baseline (=study index). Throughout the study all management
      decisions regarding antithrombotic therapy, including platelet and red blood cell
      transfusion, will be recorded. This is an observational study and management will be solely
      at the discretion of the physician.

      Analysis: The investigators will first look at the frequency of either bleeding or thrombosis
      according to the type of management strategy and evaluate the platelet threshold at which a
      given management strategy is employed.

      At the next stage, in selected subgroups, the optimal management strategy with respect to
      bleeding/thrombotic risk, will be determined.
-  Thrombocyte-level cohorts Patients will be divided into two groups based on the platelet
           level at study index .

             1. Thrombocytopenic Cohort: Patients with morning platelet count below 50*109/L at
                study index. This is the main study cohort for all analyses

             2. Non-thrombocytopenic Cohort: Patients whose morning platelet count is ≥ 50*109/L at
                study index will be considered as a reference group, and not included in the
                primary analysis.

        -  Analysis of outcomes:

      By definition, there will be an intervention at the time of study index (baseline), meaning
      that even if no change is made, it will be considered an intervention. Each patient may have
      multiple exposures/interventions over the study.

      Therefore, in a time dependent analysis, each outcome will be linked to the
      exposure/intervention at study index.

      Each exposure/intervention will be linked with the platelet level on the day of the
      intervention.

      #Competing Events:

      The following events (in addition to death) will be considered competing events and will be
      considered as such in the statistical analyses of the outcomes:

        1. The composite primary outcome

        2. change in the antithrombotic regimen after study index

        3. diagnosis of HIT or TTP

        4. a change in the hematological malignancy treatment regimen. Study follow-up will
           continue after these events, and study data will continue to be recorded until
           censorship for end of study period or death.

             -  Detecting selection bias:

      Patients fulfilling the inclusion criteria but not included in the study, will be detected by
      reviewing the medical records of the hematology institute, weekly. The baseline
      characteristics and reason for not including these patients will be recorded retrospectively
      in the "not-included cohort". The baseline characteristics of this cohort will be compared
      with the study cohort to ascertain whether selection bias exists.
observational model: Cohort
time perspective: Prospective
measure: Composite of major bleeding or thrombosis
time frame: 30 days (from study index) or until death (whichever first)
description: 1) ISTH-defined Major bleeding events defined as: Fatal bleeding; bleeding into a critical organ; clinically overt bleeding associated with a decrease in hemoglobin level of more than 2 g/dL or leading to the transfusion of two or more units of blood OR: 2) Thrombosis defined as: Any symptomatic deep or superficial venous or arterial thromboembolism demonstrated on objective imaging/laboratory tests. Ischemic strokes with no immediate imaging signs will also be considered events, provided this was diagnosed by a neurologist and that the patient had objective neurological signs.
measure: Platelet transfusion related adverse effects
time frame: 30 days (from study index) or until death (whichever first)
description: Number of adverse effects (all types and individually grouped) related to platelet/plasma transfusion, occurring within 24 hours of transfusion
measure: Clinically Relevant non-Major Bleeding
time frame: 30 days (from study index) or until death (whichever first)
description: Defined according to the ISTH criteria published in the journal of thrombosis and Hemostasis by Kaatz et al in 2015
measure: Number of platelet tranfusions
time frame: 30 days (from study index) or until death (whichever first)
description: Number of platelet transfusions
measure: Number of RBC tranfusions
time frame: 30 days (from study index) or until death (whichever first)
description: Number of red blood cell transfusions
measure: Death
time frame: 30 days (from study index)
description: death from any cause
measure: Change in antithrombotic management
time frame: 30 days (from study index) or until death (whichever first)
description: Change in dose/type of antiplatelet or anticoagulant medication OR change in platelet threshold, AFTER the initial intervention which was recorded at study index.
measure: peak anticoagulant intensity
time frame: 3 days after study index
description: anti-Xa, Hemoclot, INR, aPTT will be measured at peak, depending on the anticoagulant drug. Patients will be classified as having sub-therapeutic, therapeutic, supra-therapeutic treatment levels, based upon the reference range at the central laboratory. Only relevant for patients with anticoagulation undergoing dose change.
measure: Whole blood coagulation
time frame: 3 days after study index
description: Measured by rotational thromboelastometry (ROTEM) drawn at study index
arm group label: antiplatelet only
description: Patients receiving antiplatelet medication, but not anticoagulation. Antiplatelet drugs include any class, dose or duration of any platelet aggregation inhibitor.
This refers to the antithrombotic regimen when the current thrombocytopenia, or risk thereof (i.e. "predicted"), was first identified (even if the treatment is subsequently stopped)
arm group label: anticoagulant-based
description: Patients receiving only anticoagulants or both anticoagulant and antiplatelet medication combined. This includes any class, dose or duration of any antiplatelet or anticoagulant drug.
This refers to the antithrombotic regimen when the current thrombocytopenia, or risk thereof (i.e. "predicted"), was first identified (even if the treatment is subsequently stopped)
intervention type: Drug
intervention name: Hold
description: Hold antithrombotic therapy
arm group label: anticoagulant-based
arm group label: antiplatelet only
intervention type: Drug
intervention name: Prophylactic dose antithrombotic
description: Reduction in antithrombotic medication dose to prophylactic dose (without changing type)
arm group label: anticoagulant-based
intervention type: Drug
intervention name: Change antithrombotic Drug
description: Change in type of antithrombotic therapy
arm group label: anticoagulant-based
arm group label: antiplatelet only
intervention type: Biological
intervention name: Change platelet transfusion threshold
description: Increase or reduce platelet transfusion threshold
arm group label: anticoagulant-based
arm group label: antiplatelet only
intervention type: Drug
intervention name: Full dose antithrombotics
description: Continue full dose antithrombotic therapy
arm group label: anticoagulant-based
arm group label: antiplatelet only
intervention type: Device
intervention name: Mechanical measures
description: Mechanical measures to reduce thrombotic risk including: IVC filter insertion, Intermittent Pneumatic Compression (IPC), Removal of Central venous catheter
arm group label: anticoagulant-based
intervention type: Drug
intervention name: Intermediate dose antithrombotic
description: Reduction in antithrombotic medication dose to prophylactic dose (without changing type). Intermediate dose in between prophylactic and full dose
arm group label: anticoagulant-based
After measuring the activity of anticoagulant drugs from the plasma when doses are modified,
      remaining plasma will be retained for 5 years.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Avi Leader, MD
role: Principal Investigator
affiliation: Rabin Medical Center, Petah Tikva, Israel
last name: Hugo ten Cate, MD, PhD
role: Study Chair
affiliation: Maastricht University Medical Center, Maastricht
last name: Anna Falanga, MD
role: Study Chair
affiliation: A.O. Papa Giovanni XXIII - S.I.M.T.
last name: Avi Leader, MD
phone: +972-3-9377906
email: avileader@yahoo.com
last name: Hugo ten Cate, MD, PhD
email: h.tencate@maastrichtuniversity.nl
facility: 
status: Terminated
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
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facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
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facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
contact: 
facility: 
status: Withdrawn
country: Israel
country: Italy
country: Netherlands
country: United States
responsible party type: Sponsor
mesh term: Hematologic Neoplasms
mesh term: Thrombocytopenia