<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/NCT04430569</url>
  </required_header>
  <id_info>
    <org_study_id>P160924</org_study_id>
    <secondary_id>P160924</secondary_id>
    <secondary_id>PHRCN-16-0580</secondary_id>
    <secondary_id>2018-000816-96</secondary_id>
    <nct_id>NCT04430569</nct_id>
  </id_info>
  <brief_title>Pulmonary Embolism International THrOmbolysis Study-3</brief_title>
  <acronym>PEITHO-3</acronym>
  <official_title>A Reduced Dose of Thrombolytic Treatment for Patients With Intermediate High-risk Acute Pulmonary Embolism: a Randomized Controled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Johannes Gutenberg University Mainz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Life Sciences Research Partners (D Collen Research Foundation)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</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>
      In this study, we will assess the efficacy and safety of a reduced dose of thrombolytic&#xD;
      therapy given in addition to low-molecular-weight heparin in patients with&#xD;
      intermediate-high-risk acute pulmonary embolism. Half of participants will receive&#xD;
      thrombolytic treatment, while the other half will receive a placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with intermediate-risk pulmonary embolism, full-dose thrombolytic treatment was&#xD;
      associated with a reduction in the combined risk of hemodynamic instability or death but was&#xD;
      also associated with an increased risk of major and intracranial bleeding. Previous studies&#xD;
      suggest that reduced dose of thrombolytic treatment may be as effective as the full dosage,&#xD;
      but with a decreased risk of life-threatening bleeding. In this study, we will assess the&#xD;
      efficacy and safety of a reduced dosage of thrombolytic therapy in patients with&#xD;
      intermediate-high-risk acute pulmonary embolism.&#xD;
&#xD;
      The study is a randomized, placebo-controlled, double blind, multicenter, multinational trial&#xD;
      with long-term follow-up.&#xD;
&#xD;
      Patients fulfilling the inclusion criteria and without any of the exclusion criteria will be&#xD;
      randomized within 6 hours after the investigator had confirmed the diagnosis.&#xD;
&#xD;
      Patients will receive:&#xD;
&#xD;
        -  Alteplase (if randomized in the experimental group) or placebo (if randomized in the&#xD;
           reference group) given within 30 minutes of randomization as a 15 min intravenous&#xD;
           infusion at a dosage of 0.6 mg/kg with a total dose not exceeding 50 mg.&#xD;
&#xD;
        -  Parenteral anticoagulation with low molecular weight heparin, unfractionnated heparin or&#xD;
           fondaparinux&#xD;
&#xD;
      Primary objective is to assess the efficacy of reduced dose thrombolytic therapy in patients&#xD;
      with acute intermediate-high-risk pulmonary embolism at day 30.&#xD;
&#xD;
      Secondary objectives are:&#xD;
&#xD;
        1. To assess the safety of reduced dose thrombolytic therapy in patients with&#xD;
           intermediate-high-risk acute pulmonary embolism at day 30&#xD;
&#xD;
        2. To assess the net clinical benefit of reduced dose thrombolytic therapy in patients with&#xD;
           intermediate-high-risk acute pulmonary embolism at day 30&#xD;
&#xD;
        3. To assess the effect of reduced dose thrombolytic therapy on overall mortality of&#xD;
           patients with intermediate-high-risk acute pulmonary embolism at day 30&#xD;
&#xD;
        4. To assess the effect of reduced dose thrombolytic therapy on long-term mortality,&#xD;
           functional impairment, residual right ventricular dysfunction and chronic thromboembolic&#xD;
           pulmonary hypertension at 6 months and 2 years&#xD;
&#xD;
        5. To assess the effect of reduced-dose thrombolytic therapy on utilization of health care&#xD;
           resources at day 30 and day 180&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 4, 2021</start_date>
  <completion_date type="Anticipated">August 2027</completion_date>
  <primary_completion_date type="Anticipated">September 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of (1) death from any cause or (2) hemodynamic decompensation or (3) objectively confirmed recurrent PE.</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fatal or GUSTO severe or life threatening bleeding</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of the primary efficacy endpoint and GUSTO severe or life-threatening bleeding</measure>
    <time_frame>30 days</time_frame>
    <description>Assessment of net clinical benefit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PE related death</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemodynamic decompensation</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrent PE</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for rescue thrombolysis, catheter-directed treatment or surgical embolectomy</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ischemic or hemorrhagic stroke</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persisting dyspnea</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persisting dyspnea</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent right ventricular dysfunction</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent right ventricular dysfunction</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome</measure>
    <time_frame>180 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Confirmed chronic thromboembolic pulmonary hypertension</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Utilization of health care ressources</measure>
    <time_frame>30 days</time_frame>
    <description>Questionnaire assessing the impact of the treatment on utilization of health care ressources</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Utilization of health care ressources</measure>
    <time_frame>180 days</time_frame>
    <description>Questionnaire assessing the impact of the treatment on utilization of health care ressources</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">650</enrollment>
  <condition>Pulmonary Embolism</condition>
  <arm_group>
    <arm_group_label>Alteplase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alteplase</intervention_name>
    <description>Alteplase single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.</description>
    <arm_group_label>Alteplase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Objectively confirmed acute PE with first symptoms occurring 2 weeks or less before&#xD;
             randomization. Objective confirmation is based on at least one of the following&#xD;
             criteria: (a) at least one segmental ventilation-perfusion mismatch on lung scanning;&#xD;
             (b) a spiral computed tomography pulmonary angiography or pulmonary angiography&#xD;
             showing a filling defect or an abrupt obstruction of a segmental or more proximal&#xD;
             pulmonary artery&#xD;
&#xD;
          -  Acute PE confirmed within 24 hours prior to randomization&#xD;
&#xD;
          -  Elevated risk of early death, or of hemodynamic collapse, or PE recurrence, indicated&#xD;
             by at least one of the following criteria: (a) systolic blood pressure ≤ 110 mm Hg&#xD;
             over at least 15 minutes upon enrolment, (b) temporary need for fluid resuscitation&#xD;
             and/or treatment with low-dose catecholamines, provided that the patient could be&#xD;
             stabilized within 2 hours of admission and maintains SBP of ≥ 90 mmHg and adequate&#xD;
             organ perfusion without catecholamine infusion; (c) respiratory rate &gt; 20/min or&#xD;
             oxygen saturation on pulse oximetry SpO2 &lt;90% o(or partial arterial oxygen pressure &lt;&#xD;
             60 mm Hg) at rest while breathing room air, (d) history of chronic heart failure&#xD;
&#xD;
          -  Right ventricular dysfunction indicated by RV/LV diameter ratio &gt;1.0 on&#xD;
             echocardiography apical four-chamber or subcostal four-chamber view or on Computed&#xD;
             Tomography Pulmonary Angiography (transverse plane)&#xD;
&#xD;
          -  Serum troponin I or T concentration above the upper limit of local normal using a&#xD;
             high-sensitivity assay&#xD;
&#xD;
          -  Ability to randomize the patient within 6 hours after the investigator receives the&#xD;
             results of the second of the two criteria for RV dysfunction (RV/LV diameter ratio&#xD;
             &gt;1.0) and myocardial injury (serum troponin I or T concentration above the upper limit&#xD;
             of local normal), whichever comes latest.&#xD;
&#xD;
          -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hemodynamic instability&#xD;
&#xD;
          -  Active bleeding&#xD;
&#xD;
          -  History of non-traumatic intracranial bleeding, any time&#xD;
&#xD;
          -  Acute ischemic stroke or transient ischemic attack (TIA) within the previous 6 months&#xD;
&#xD;
          -  Known central nervous system neoplasm/metastasis&#xD;
&#xD;
          -  Neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic&#xD;
             surgery or trauma within 3 previous weeks&#xD;
&#xD;
          -  Platelet count &lt; 100 G/L&#xD;
&#xD;
          -  INR &gt; 1.4&#xD;
&#xD;
          -  Treatment with antiplatelet agents other than (a) acetylsalicylic acid (ASA) ≤ 100 mg&#xD;
             once daily or (b) clopidogrel 75 mg once daily or (c) a single loading dose of ASA or&#xD;
             clopidogrel. Dual antiplatelet therapy (ASA + clopidogrel) is not allowed.&#xD;
&#xD;
          -  Any direct oral anticoagulant within 12 hours of inclusion&#xD;
&#xD;
          -  Uncontrolled hypertension &gt; 180/90 mm Hg at the time of inclusion&#xD;
&#xD;
          -  Known pericarditis or endocarditis&#xD;
&#xD;
          -  Known significant bleeding risk according to the investigator's judgement&#xD;
&#xD;
          -  Administration of thrombolytic agents within the previous 4 days&#xD;
&#xD;
          -  Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days&#xD;
&#xD;
          -  Current participation in another interventional clinical study&#xD;
&#xD;
          -  Previous enrolment in this study&#xD;
&#xD;
          -  Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse®&#xD;
             manufacturing process present in trace amounts), any of the excipients of Actilyse®,&#xD;
             or low-molecular weight heparin (LMWH)&#xD;
&#xD;
          -  Known previous immune heparin-induced thrombocytopenia&#xD;
&#xD;
          -  Known severe liver disease (grade ≥ 3) including liver failure, cirrhosis, portal&#xD;
             hypertension (esophageal varices) and active hepatitis&#xD;
&#xD;
          -  Acute symptomatic pancreatitis&#xD;
&#xD;
          -  Gastrointestinal ulcers or esophageal varices, documented within the past 3 months&#xD;
&#xD;
          -  Known arterial aneurysm, arterial or venous malformations&#xD;
&#xD;
          -  Pregnancy or parturition within the previous 30 days or current breastfeeding.&#xD;
&#xD;
          -  Women of childbearing potential who do not have a negative pregnancy test and do not&#xD;
             use one of the following methods of birth control: hormonal contraception or&#xD;
             intrauterine device or bilateral tubal occlusion&#xD;
&#xD;
          -  Any other condition that the investigator feels would place the patient at increased&#xD;
             risk upon start of the investigational treatment&#xD;
&#xD;
          -  Life expectancy of less than 6 months or inability to complete 6-month follow-up.&#xD;
&#xD;
          -  Patient under legal protection&#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>Olivier SANCHEZ, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stavros Konstantinides, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Mainz</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Olivier SANCHEZ, MD PhD</last_name>
    <email>olivier.sanchez@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yvann Frigout</last_name>
    <email>yvann.frigout@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Graz, Mediz Universität</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Zirlik, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ordensklinikum Linz GmbH Elisabethinen</name>
      <address>
        <city>Linz</city>
        <zip>4020</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Regina Steringer-Mascherbauer, MD</last_name>
      <email>regina.steringer-mascherbauer@ordensklinikum.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>UCL Brussels</name>
      <address>
        <city>Bruxelles</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Franck Verschuren, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>KU Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Thomas Vanassche, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Liège</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alexandre Ghuysen, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kevin Solverson, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences Corporation</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sam Schulman, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kingston Health Sciences Centre</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kerstin de Wit, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Justin Yan, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hopsital, General and Civic campuses</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lana Castellucci, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Andrew Hirsch, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU d'Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre-Marie Roy, MD</last_name>
      <email>pmroy@chu-angers.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Besançon - Hôpital Jean-Minjoz</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolas Meneveau, MD</last_name>
      <email>nicolas.meneveau@univ-fcomte.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Brest - Hôpital de la Cavale Blanche</name>
      <address>
        <city>Brest</city>
        <zip>29000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francis Couturaud, MD</last_name>
      <email>francis.couturaud@chu-brest.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Tours - Hôpital Trousseau</name>
      <address>
        <city>Chambray-lès-Tours</city>
        <zip>37170</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Denis Angoulvant, MD</last_name>
      <email>d.angoulvant@chu-tours.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand - Hôpital Gabriel Montpied</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeannot Schmidt, MD</last_name>
      <email>jschmidt@chu-clermontferrand.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AP-HP - hôpital Henri-Mondor</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascal Lim, MD</last_name>
      <email>pascal.lim@aphp.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble - Hôpital Michallon</name>
      <address>
        <city>La Tronche</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hélène Bouvaist, MD</last_name>
      <email>hbouvaist@chu-grenoble.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AP-HP - hôpital Bicêtre</name>
      <address>
        <city>Le Kremlin-Bicêtre</city>
        <zip>94270</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurent Savale, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Lille - Institut Cœur Poumon</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolas Lemblin, MD</last_name>
      <email>nicolas.lamblin@chru-lille.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HCL - Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karim Tazarourte, MD</last_name>
      <email>karim.tazarourte@chu-lyon.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HCL - Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurent Argaud, MD</last_name>
      <email>laurent.argaud@chu-lyon.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AP-HM - Hôpital de la Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gabrielle Sarlon-Bartoli, MD</last_name>
      <email>gabrielle.sarlon@ap-hm.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Montpellier - Hôpital Lapeyronie</name>
      <address>
        <city>Montpellier</city>
        <zip>34000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mustapha Sebbane, MD</last_name>
      <email>m-sebbane@chu-montpellier.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Nice - Hôpital Pasteur</name>
      <address>
        <city>Nice</city>
        <zip>06000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emile Ferrari, MD</last_name>
      <email>ferrari.e@chu-nice.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>AP-HP - hôpital européen Georges-Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benjamin Planquette, MD</last_name>
      <email>benjamin.planquette@aphp.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital Bichat-Claude-Bernard</name>
      <address>
        <city>Paris</city>
        <zip>75018</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Grégory Ducrocq, MD</last_name>
      <email>gregory.ducrocq@aphp.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AP-HP - Hôpital Tenon</name>
      <address>
        <city>Paris</city>
        <zip>75020</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aude Gibelin, MD</last_name>
      <email>aude.gibelin@aphp.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HCL - Centre Hospitalier Lyon-Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marion Douplat, MD</last_name>
      <email>marion.douplat@chu-lyon.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Saint-Étienne - Hôpital Nord</name>
      <address>
        <city>Saint-Étienne</city>
        <zip>42055</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurent Bertoletti, MD</last_name>
      <email>laurent.bertoletti@chu-st-etienne.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Strasbourg - Hôpital Civil</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick Ohlmann, MD</last_name>
      <email>patrick.ohlmann@chu-strasbourg.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse - Hôpital Rangueil</name>
      <address>
        <city>Toulouse</city>
        <zip>31000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caroline Biendel-Piquet, MD</last_name>
      <email>biendel.c@chu-toulouse.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitäts-Herzzentrum Freiburg - Bad Krozingen</name>
      <address>
        <city>Bad Krozingen</city>
        <zip>79189</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philipp Breitbart, MD</last_name>
      <email>philipp.breitbart@uniklinik-freiburg.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>DRK Kliniken Berlin Köpenick</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dirk Habedank, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Berlin, DRK Kliniken Westend</name>
      <address>
        <city>Berlin</city>
        <zip>14050</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Opitz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dresden, Städtisches Klinikum</name>
      <address>
        <city>Dresden</city>
        <zip>01067</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sebastian Schellong, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Düsseldorf, Augusta-Krankenhaus</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40472</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Anamaria Wolf-Pütz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Freiburg Universität</name>
      <address>
        <city>Freiburg</city>
        <zip>79085</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel Dürschmied, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Greifswald, Univ.-Medizin</name>
      <address>
        <city>Greifswald</city>
        <zip>17489</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ralf Eswert, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hannover, Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andreas Schäfer, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Augustinerinnen Hospital</name>
      <address>
        <city>Köln</city>
        <zip>50678</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ingo Ahrens, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cologne Universität Herzzentrum</name>
      <address>
        <city>Köln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Stephan Rosenkranz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Leipzig, Univ.-Klinikum</name>
      <address>
        <city>Leipzig</city>
        <zip>4103</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Holger Thiele, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Mainz Universitätsmedizin, CTH</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stavros Konstantinides, MD</last_name>
      <email>stavros.konstantinides@unimedizin-mainz.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Mainz, Katholisches Klinikum</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sabine Genth-Zotz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Mannheim UMM</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ibrahim Akin, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Regensburg, Uniklinik</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tobias Lange, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tübingen, Univ.-Klinikum</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tobias Geisler, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ulm, Universitätsklinikum</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Armin Imhof, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital Ancona / Ospedali Riunit</name>
      <address>
        <city>Ancona</city>
        <zip>60020</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aldo Salvi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Poliambulanza Hospital - Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25124</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudio Cuccia, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Spedali Riuniti - Cremona</name>
      <address>
        <city>Cremona</city>
        <zip>26100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Enrico Passamonti, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale San Giuseppe - Empoli</name>
      <address>
        <city>Empoli</city>
        <zip>50053</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Simone Vanni, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Careggi - Firenze</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maddalena Ottaviani, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Poma - Mantova</name>
      <address>
        <city>Mantova</city>
        <zip>46100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antonio Izzo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Humanitas Hospital - Milano</name>
      <address>
        <city>Milano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Corrado Lodigiani, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Perugia</name>
      <address>
        <city>Perugia</city>
        <zip>06123</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Cecilia Becattini, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Ca Foncello - Treviso</name>
      <address>
        <city>Treviso</city>
        <zip>31100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele Diamanti, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Haaglanden hospital</name>
      <address>
        <city>Den Haag</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Catharina hospital</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Medisch Spectrum Twente</name>
      <address>
        <city>Enschede</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Martini hospital</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Maasstad hospital</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Antonius hospital</name>
      <address>
        <city>Sneek</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Isala hospital</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Medical University of Bialystok</name>
      <address>
        <city>Białystok</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bożena Sobkowicz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Department of Cardiac and Vascular Diseases</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Piotr Podolec, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Poznan University of Medical Sciences</name>
      <address>
        <city>Poznań</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Tatiana Mularek, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medical University of Warsaw</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Zbigniew Gaciong, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medical University of Lodz</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jarosław Kasprzak, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Garcia de Orta</name>
      <address>
        <city>Almada</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Melanie Ferreira, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar de Lisboa Norte/ Hospitalde Santa Maria</name>
      <address>
        <city>Lisboa</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Rui Placido, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar de Lisboa Ocidental</name>
      <address>
        <city>Lisboa</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Hugo Moreira, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Pedro Hispano</name>
      <address>
        <city>Matosinhos</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Carolina Guedes, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar do Porto</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Fabienne Gonçalves, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar de Setubal</name>
      <address>
        <city>Setúbal</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sonia Serra, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Spitalul Judetean de Urgenta Baia Mare</name>
      <address>
        <city>Baia Mare</city>
        <zip>430031</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Calin Pop, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Bucuresti - Spitalul Clinic de Urgenta Sf. Pantelimon</name>
      <address>
        <city>Bucuresti</city>
        <country>Romania</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alexandru Nechita, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Spitalul Judetean de Urgenta Constanta</name>
      <address>
        <city>Constanţa</city>
        <zip>900591</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Anca Mihaela Radulescu, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Iasi - St Spiridon Emergency Conty Hospital</name>
      <address>
        <city>Iaşi</city>
        <zip>700111</zip>
        <country>Romania</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antoniu Petris, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institutul de Boli Cardio-Vasculare Timisoara</name>
      <address>
        <city>Timişoara</city>
        <country>Romania</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lucian Petrescu, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cardiology Clinic, Emergency Center, Clinical Center of Serbia</name>
      <address>
        <city>Belgrad</city>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Branislav Stefanovic, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cardiology Clinic, Clinical Center of Niš</name>
      <address>
        <city>Niš</city>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Institute for Lung Diseases of Vojvodina, Sremska Kamenica</name>
      <address>
        <city>Novi Sad</city>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Medical Centre Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <zip>1000</zip>
        <country>Slovenia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matija Kozak, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuel Monreal, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jorge Moises, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Bellvitge</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoni Riera-Mestre, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Cartagena</name>
      <address>
        <city>Cartagena</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Javier Trujillo-Santos, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Galdakao</name>
      <address>
        <city>Galdakao</city>
        <zip>48960</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aitor Ballaz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clínica Universitaria Navarra</name>
      <address>
        <city>Madrid</city>
        <zip>28027</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pedro Ruiz-Artacho, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Jimenez, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Remedios Otero, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Raquel Lopez, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Araba</name>
      <address>
        <city>Vitoria</city>
        <zip>01009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jose Luis Lobo, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital fribourgeois</name>
      <address>
        <city>Fribourg</city>
        <zip>1752</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Daniel Hayoz, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Geneva University Hospital</name>
      <address>
        <city>Geneva</city>
        <zip>1205</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Marc Righini, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Lausanne University Hospital</name>
      <address>
        <city>Lausanne</city>
        <zip>1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lucia Mazzolai, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Serbia</country>
    <country>Slovenia</country>
    <country>Spain</country>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.</citation>
    <PMID>24716681</PMID>
  </reference>
  <reference>
    <citation>Barco S, Vicaut E, Klok FA, Lankeit M, Meyer G, Konstantinides SV; PEITHO Investigators. Improved identification of thrombolysis candidates amongst intermediate-risk pulmonary embolism patients: implications for future trials. Eur Respir J. 2018 Jan 18;51(1):1701775. doi: 10.1183/13993003.01775-2017. Print 2018 Jan. No abstract available.</citation>
    <PMID>29348184</PMID>
  </reference>
  <reference>
    <citation>Konstantinides SV, Vicaut E, Danays T, Becattini C, Bertoletti L, Beyer-Westendorf J, Bouvaist H, Couturaud F, Dellas C, Duerschmied D, Empen K, Ferrari E, Galie N, Jimenez D, Kostrubiec M, Kozak M, Kupatt C, Lang IM, Lankeit M, Meneveau N, Palazzini M, Pruszczyk P, Rugolotto M, Salvi A, Sanchez O, Schellong S, Sobkowicz B, Meyer G. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol. 2017 Mar 28;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039.</citation>
    <PMID>28335835</PMID>
  </reference>
  <reference>
    <citation>Marti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, Meyer G, Perrier A. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605-14. doi: 10.1093/eurheartj/ehu218. Epub 2014 Jun 10.</citation>
    <PMID>24917641</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>June 7, 2023</last_update_submitted>
  <last_update_submitted_qc>June 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intermediate-high-risk acute pulmonary embolism</keyword>
  <keyword>Thrombolysis</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>Tissue Plasminogen Activator</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>One year after the last publication</ipd_time_frame>
    <ipd_access_criteria>Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team. The founder could be involved in the decision.&#xD;
Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04430569
org study id: P160924
secondary id: P160924
secondary id: PHRCN-16-0580
secondary id: 2018-000816-96
nct id: NCT04430569
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this study, we will assess the efficacy and safety of a reduced dose of thrombolytic
      therapy given in addition to low-molecular-weight heparin in patients with
      intermediate-high-risk acute pulmonary embolism. Half of participants will receive
      thrombolytic treatment, while the other half will receive a placebo.
In patients with intermediate-risk pulmonary embolism, full-dose thrombolytic treatment was
      associated with a reduction in the combined risk of hemodynamic instability or death but was
      also associated with an increased risk of major and intracranial bleeding. Previous studies
      suggest that reduced dose of thrombolytic treatment may be as effective as the full dosage,
      but with a decreased risk of life-threatening bleeding. In this study, we will assess the
      efficacy and safety of a reduced dosage of thrombolytic therapy in patients with
      intermediate-high-risk acute pulmonary embolism.

      The study is a randomized, placebo-controlled, double blind, multicenter, multinational trial
      with long-term follow-up.

      Patients fulfilling the inclusion criteria and without any of the exclusion criteria will be
      randomized within 6 hours after the investigator had confirmed the diagnosis.

      Patients will receive:

        -  Alteplase (if randomized in the experimental group) or placebo (if randomized in the
           reference group) given within 30 minutes of randomization as a 15 min intravenous
           infusion at a dosage of 0.6 mg/kg with a total dose not exceeding 50 mg.

        -  Parenteral anticoagulation with low molecular weight heparin, unfractionnated heparin or
           fondaparinux

      Primary objective is to assess the efficacy of reduced dose thrombolytic therapy in patients
      with acute intermediate-high-risk pulmonary embolism at day 30.

      Secondary objectives are:

        1. To assess the safety of reduced dose thrombolytic therapy in patients with
           intermediate-high-risk acute pulmonary embolism at day 30

        2. To assess the net clinical benefit of reduced dose thrombolytic therapy in patients with
           intermediate-high-risk acute pulmonary embolism at day 30

        3. To assess the effect of reduced dose thrombolytic therapy on overall mortality of
           patients with intermediate-high-risk acute pulmonary embolism at day 30

        4. To assess the effect of reduced dose thrombolytic therapy on long-term mortality,
           functional impairment, residual right ventricular dysfunction and chronic thromboembolic
           pulmonary hypertension at 6 months and 2 years

        5. To assess the effect of reduced-dose thrombolytic therapy on utilization of health care
           resources at day 30 and day 180
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Composite of (1) death from any cause or (2) hemodynamic decompensation or (3) objectively confirmed recurrent PE.
time frame: 30 days
measure: Fatal or GUSTO severe or life threatening bleeding
time frame: 30 days
measure: Composite of the primary efficacy endpoint and GUSTO severe or life-threatening bleeding
time frame: 30 days
description: Assessment of net clinical benefit
measure: All-cause mortality
time frame: 30 days
measure: PE related death
time frame: 30 days
measure: Hemodynamic decompensation
time frame: 30 days
measure: Recurrent PE
time frame: 30 days
measure: Need for rescue thrombolysis, catheter-directed treatment or surgical embolectomy
time frame: 30 days
measure: Ischemic or hemorrhagic stroke
time frame: 30 days
measure: Serious adverse events
time frame: 30 days
measure: Persisting dyspnea
time frame: 180 days
measure: Persisting dyspnea
time frame: 2 years
measure: Persistent right ventricular dysfunction
time frame: 180 days
measure: Persistent right ventricular dysfunction
time frame: 2 years
measure: Functional outcome
time frame: 180 days
measure: Functional outcome
time frame: 2 years
measure: All-cause mortality
time frame: 2 years
measure: Confirmed chronic thromboembolic pulmonary hypertension
time frame: 2 years
measure: Utilization of health care ressources
time frame: 30 days
description: Questionnaire assessing the impact of the treatment on utilization of health care ressources
measure: Utilization of health care ressources
time frame: 180 days
description: Questionnaire assessing the impact of the treatment on utilization of health care ressources
arm group label: Alteplase
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Alteplase
description: Alteplase single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
arm group label: Alteplase
intervention type: Drug
intervention name: Placebo
description: Placebo single intravenous infusion of 0.6 mg/kg of estimated bodyweight with a maximum of 50 mg given over 15 minutes.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Olivier SANCHEZ, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Stavros Konstantinides, MD
role: Principal Investigator
affiliation: University Medical Center Mainz
last name: Olivier SANCHEZ, MD PhD
email: olivier.sanchez@aphp.fr
last name: Yvann Frigout
email: yvann.frigout@aphp.fr
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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facility: 
status: Recruiting
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status: Recruiting
contact: 
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status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
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
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
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facility: 
status: Not yet recruiting
contact: 
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status: Not yet recruiting
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status: Not yet recruiting
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status: Recruiting
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status: Not yet recruiting
contact: 
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status: Recruiting
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status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
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status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
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facility: 
status: Not yet recruiting
contact: 
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
contact: 
country: Austria
country: Belgium
country: Canada
country: France
country: Germany
country: Italy
country: Netherlands
country: Poland
country: Portugal
country: Romania
country: Serbia
country: Slovenia
country: Spain
country: Switzerland
citation: Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
PMID: 24716681
citation: Barco S, Vicaut E, Klok FA, Lankeit M, Meyer G, Konstantinides SV; PEITHO Investigators. Improved identification of thrombolysis candidates amongst intermediate-risk pulmonary embolism patients: implications for future trials. Eur Respir J. 2018 Jan 18;51(1):1701775. doi: 10.1183/13993003.01775-2017. Print 2018 Jan. No abstract available.
PMID: 29348184
citation: Konstantinides SV, Vicaut E, Danays T, Becattini C, Bertoletti L, Beyer-Westendorf J, Bouvaist H, Couturaud F, Dellas C, Duerschmied D, Empen K, Ferrari E, Galie N, Jimenez D, Kostrubiec M, Kozak M, Kupatt C, Lang IM, Lankeit M, Meneveau N, Palazzini M, Pruszczyk P, Rugolotto M, Salvi A, Sanchez O, Schellong S, Sobkowicz B, Meyer G. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol. 2017 Mar 28;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039.
PMID: 28335835
citation: Marti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, Meyer G, Perrier A. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605-14. doi: 10.1093/eurheartj/ehu218. Epub 2014 Jun 10.
PMID: 24917641
responsible party type: Sponsor
mesh term: Pulmonary Embolism
mesh term: Embolism
mesh term: Tissue Plasminogen Activator
sharing ipd: Yes
ipd description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: One year after the last publication
ipd access criteria: Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team. The founder could be involved in the decision.
Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.