<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/NCT01727427</url>
  </required_header>
  <id_info>
    <org_study_id>215/2012</org_study_id>
    <nct_id>NCT01727427</nct_id>
  </id_info>
  <brief_title>Prospective Study on the Treatment of Unsuspected Pulmonary Embolism in Cancer Patients</brief_title>
  <official_title>Prospective Study on the Treatment of Unsuspected Pulmonary Embolism in Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>G. d'Annunzio University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>G. d'Annunzio University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The same initial and long-term anticoagulation is suggested for unsuspected pulmonary&#xD;
      embolism as for patients with symptomatic embolism. Based on these indications, cancer&#xD;
      patients with unsuspected pulmonary embolism would be anticoagulated for at least 6 months or&#xD;
      until the disease is active, which in most cases would mean indefinite treatment. In fact,&#xD;
      dedicated studies on the treatment of unsuspected pulmonary embolism are missing, leaving&#xD;
      doubts over the need for (indefinite) anticoagulation which exposes these patients to an&#xD;
      increased risk of major bleeding events. Concerns over the need for anticoagulant treatment&#xD;
      may especially hold for pulmonary embolism of the distal pulmonary tree since segmental and&#xD;
      sub-segmental PE seem to have a more benign course than more proximal embolism.&#xD;
&#xD;
      The scope of this study is to evaluate the current treatment approaches for unsuspected&#xD;
      pulmonary embolism and to assess their efficacy and safety in a large prospective cohort of&#xD;
      cancer patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">December 2017</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrent (symptomatic) vein thromboembolism, including pulmonary embolism and deep vein thrombosis</measure>
    <time_frame>one year</time_frame>
    <description>Suspected recurrent PE with one of the following:&#xD;
new intra-luminal filling defect on CT scan, MRI scan, or pulmonary angiogram;&#xD;
new perfusion defect of at least 75% on V/Q lung scan;&#xD;
inconclusive spiral CT, pulmonary angiography or lung scan with demonstration of DVT in the lower extremities by CUS or venography&#xD;
Fatal PE is:&#xD;
PE based on objective diagnostic testing or autopsy or&#xD;
death not attributed to a documented cause and for which DVT/PE cannot be ruled out.&#xD;
Suspected (recurrent) DVT with one of the following findings:&#xD;
abnormal CUS;&#xD;
an intra-luminal filling defect on venography.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Major, clinically relevant non-major bleeding, and minor bleeding</measure>
    <time_frame>one year</time_frame>
    <description>Major bleeding will be defined as overt bleeding associated with: a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or bleeding that occurs in a critical site: intracranial, intra-spinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal or contributing to death.&#xD;
Other clinically relevant non-major bleeding will be defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary) cessation of study treatment, or associated with discomfort for the patient such as pain, or impairment of activities of daily life. All other bleeding events will be classified as minor.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mortality</measure>
    <time_frame>one year</time_frame>
    <description>Overall mortality</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">695</enrollment>
  <condition>Unsuspected Pulmonary Embolism</condition>
  <arm_group>
    <arm_group_label>Anticoagulants, aspirin</arm_group_label>
    <description>Parenteral or oral anticoagulants: heparin, fondaparinux, vitamin-K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors; aspirin. Any dosage, frequency and duration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Heparin, fondaparinux, vitamin-K antagonists, aspirin</intervention_name>
    <description>Parenteral or oral anticoagulant Antiplatelet agent</description>
    <arm_group_label>Anticoagulants, aspirin</arm_group_label>
    <other_name>Enoxaparin (Clexane)</other_name>
    <other_name>Dalteparin (Fragmin)</other_name>
    <other_name>Nadroparin (Fraxiparin)</other_name>
    <other_name>Tinzaparin (Innohep)</other_name>
    <other_name>Bemiparin (Ivor)</other_name>
    <other_name>Fondaparinux (Arixtra)</other_name>
    <other_name>Warfarin (Coumadin)</other_name>
    <other_name>Acenocoumarol (Sintrom)</other_name>
    <other_name>Phenprocoumon (Marcoumar)</other_name>
    <other_name>Acetylsalicylic acid (Aspirin)</other_name>
    <other_name>Dabigatran (Pradaxa)</other_name>
    <other_name>Rivaroxaban (Xarelto)</other_name>
    <other_name>Apixaban (Eliquis)</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All ambulatory or hospitalized cancer patients with a first diagnosis of unsuspected PE.&#xD;
        Both solid and hematological cancers at any stage of disease will be considered for&#xD;
        inclusion&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  cancer patients with a first diagnosis of unsuspected PE&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. age &lt;18 years;&#xD;
&#xD;
          2. ongoing anticoagulant therapy for previous VTE or indications for long-term&#xD;
             anticoagulation other than deep vein thrombosis (DVT) or PE;&#xD;
&#xD;
          3. life expectancy less than 3 months.&#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>Marcello Di Nisio, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>D.C. Veterans Affairs Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Division of Haematology, Department of Medicine I</name>
      <address>
        <city>Vienna</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Division of Hematology, University of Ottawa</name>
      <address>
        <city>Ottawa</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Amiens Picardie</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arras/Onco Nord Pas de Callais, Loos</name>
      <address>
        <city>Arras</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint André</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University hospital Centra La Cavale Blanche</name>
      <address>
        <city>Brest, Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brest HIA Clermont Tonnerre</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montpellier et clinique du parc a Castelnau le nez</name>
      <address>
        <city>Castelnau</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital G. Montpied Clermont-Ferrand</name>
      <address>
        <city>Clermont</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP Hopital Louis Mourier</name>
      <address>
        <city>Colombes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laboratoire d'Hématologie, Dijon</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon-Sud</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Europeen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Loriboisière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pitie Salpetriere</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Service de médecine et Thérapeutique</name>
      <address>
        <city>Saint-Etienne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Division of Vascular Medicine, Department of Medicine, Technical University Dresden</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedali Riuniti</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universita degli Studi G. d'Annunzio Chieti e Pescara</name>
      <address>
        <city>Chieti</city>
        <zip>66100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Malattie Cardiovascolari e Nefrourologiche</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Arcispedale Santa Maria Nuova (ASMN)</name>
      <address>
        <city>Reggio Emilia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università dell'Insubria</name>
      <address>
        <city>Varese</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Slotervaart hospital</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 EC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute - Antonie van Leeuwenhoek hospital</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic i Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Sabadell</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall D'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO_Hospital Duran i Reynals</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Benidorm, Alicante</name>
      <address>
        <city>Benidorm</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Insular de Gran Canarias</name>
      <address>
        <city>Las Palmas</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Móstoles</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Infantia Sofia</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro Majadahonda</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario San Carlos</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa María Nei</name>
      <address>
        <city>Orense</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Obispo Polanco</name>
      <address>
        <city>Teruel</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nuestra Sra del Prado Talavera de la Reina</name>
      <address>
        <city>Toledo</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Dr. Peset</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <last_update_submitted>August 7, 2019</last_update_submitted>
  <last_update_submitted_qc>August 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>G. d'Annunzio University</investigator_affiliation>
    <investigator_full_name>Marcello Di Nisio</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Unsuspected</keyword>
  <keyword>pulmonary embolism</keyword>
  <keyword>cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Embolism</mesh_term>
    <mesh_term>Embolism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Vitamin K</mesh_term>
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Dalteparin</mesh_term>
    <mesh_term>Tinzaparin</mesh_term>
    <mesh_term>PENTA</mesh_term>
    <mesh_term>Nadroparin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Rivaroxaban</mesh_term>
    <mesh_term>Dabigatran</mesh_term>
    <mesh_term>Apixaban</mesh_term>
    <mesh_term>Fondaparinux</mesh_term>
    <mesh_term>Acenocoumarol</mesh_term>
    <mesh_term>Phenprocoumon</mesh_term>
    <mesh_term>Bemiparin</mesh_term>
  </intervention_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/NCT01727427
org study id: 215/2012
nct id: NCT01727427
lead sponsor: 
has dmc: Yes
The same initial and long-term anticoagulation is suggested for unsuspected pulmonary
      embolism as for patients with symptomatic embolism. Based on these indications, cancer
      patients with unsuspected pulmonary embolism would be anticoagulated for at least 6 months or
      until the disease is active, which in most cases would mean indefinite treatment. In fact,
      dedicated studies on the treatment of unsuspected pulmonary embolism are missing, leaving
      doubts over the need for (indefinite) anticoagulation which exposes these patients to an
      increased risk of major bleeding events. Concerns over the need for anticoagulant treatment
      may especially hold for pulmonary embolism of the distal pulmonary tree since segmental and
      sub-segmental PE seem to have a more benign course than more proximal embolism.

      The scope of this study is to evaluate the current treatment approaches for unsuspected
      pulmonary embolism and to assess their efficacy and safety in a large prospective cohort of
      cancer patients.
observational model: Cohort
time perspective: Prospective
measure: Recurrent (symptomatic) vein thromboembolism, including pulmonary embolism and deep vein thrombosis
time frame: one year
description: Suspected recurrent PE with one of the following:
new intra-luminal filling defect on CT scan, MRI scan, or pulmonary angiogram;
new perfusion defect of at least 75% on V/Q lung scan;
inconclusive spiral CT, pulmonary angiography or lung scan with demonstration of DVT in the lower extremities by CUS or venography
Fatal PE is:
PE based on objective diagnostic testing or autopsy or
death not attributed to a documented cause and for which DVT/PE cannot be ruled out.
Suspected (recurrent) DVT with one of the following findings:
abnormal CUS;
an intra-luminal filling defect on venography.
measure: Major, clinically relevant non-major bleeding, and minor bleeding
time frame: one year
description: Major bleeding will be defined as overt bleeding associated with: a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or bleeding that occurs in a critical site: intracranial, intra-spinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal or contributing to death.
Other clinically relevant non-major bleeding will be defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary) cessation of study treatment, or associated with discomfort for the patient such as pain, or impairment of activities of daily life. All other bleeding events will be classified as minor.
measure: Mortality
time frame: one year
description: Overall mortality
arm group label: Anticoagulants, aspirin
description: Parenteral or oral anticoagulants: heparin, fondaparinux, vitamin-K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors; aspirin. Any dosage, frequency and duration
intervention type: Drug
intervention name: Heparin, fondaparinux, vitamin-K antagonists, aspirin
description: Parenteral or oral anticoagulant Antiplatelet agent
arm group label: Anticoagulants, aspirin
other name: Enoxaparin (Clexane)
other name: Dalteparin (Fragmin)
other name: Nadroparin (Fraxiparin)
other name: Tinzaparin (Innohep)
other name: Bemiparin (Ivor)
other name: Fondaparinux (Arixtra)
other name: Warfarin (Coumadin)
other name: Acenocoumarol (Sintrom)
other name: Phenprocoumon (Marcoumar)
other name: Acetylsalicylic acid (Aspirin)
other name: Dabigatran (Pradaxa)
other name: Rivaroxaban (Xarelto)
other name: Apixaban (Eliquis)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marcello Di Nisio, MD, PhD
role: Principal Investigator
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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country: Austria
country: Canada
country: France
country: Germany
country: Italy
country: Netherlands
country: Spain
country: United States
responsible party type: Principal Investigator
investigator affiliation: G. d'Annunzio University
investigator full name: Marcello Di Nisio
investigator title: Principal Investigator
mesh term: Pulmonary Embolism
mesh term: Embolism
mesh term: Aspirin
mesh term: Vitamin K
mesh term: Heparin
mesh term: Enoxaparin
mesh term: Dalteparin
mesh term: Tinzaparin
mesh term: PENTA
mesh term: Nadroparin
mesh term: Warfarin
mesh term: Rivaroxaban
mesh term: Dabigatran
mesh term: Apixaban
mesh term: Fondaparinux
mesh term: Acenocoumarol
mesh term: Phenprocoumon
mesh term: Bemiparin