<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/NCT01705808</url>
  </required_header>
  <id_info>
    <org_study_id>OSR/40/04/12</org_study_id>
    <nct_id>NCT01705808</nct_id>
  </id_info>
  <brief_title>Administration of Protein C Concentrates in Adult Critically Ill Septic Patients</brief_title>
  <official_title>Administration of Protein C Concentrates in Adult Critically Ill Septic Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Università Vita-Salute San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Università Vita-Salute San Raffaele</source>
  <brief_summary>
    <textblock>
      Severe sepsis and septic shock are life threatening medical emergencies and are among the&#xD;
      most significant challenges in critical care. Case reports and case series suggest that&#xD;
      plasma-derived protein C concentrate may improve the outcome of patients with acquired&#xD;
      protein C deficiency. Evidence has accumulated on the clinical relevance of the PC pathway in&#xD;
      modulating overwhelming inflammation and preventing coagulation derangements, two key&#xD;
      mediators of organ damage, and thus of mortality and morbidity, in sepsis. The experience&#xD;
      collected through these studies shows that PC is safe, in that it is not associated with&#xD;
      bleeding or severe allergic complications,and possibly useful, at least to improve the&#xD;
      coagulation abnormalities brought about by sepsis. Unfortunately, however, all we know comes&#xD;
      from case series or case reports or an underpowered randomized controlled study. A randomized&#xD;
      clinical trial, adequately powered for mortality or clinically relevant outcome, is necessary&#xD;
      to confirm PC efficacy.The aim of this study is to demonstrate that Protein C zymogen has&#xD;
      clinically relevant implications in terms of reduction of thromboembolic events, 30 days&#xD;
      mortality, length of intensive care and hospital stay, time on mechanical ventilation, length&#xD;
      of ICU and hospital stay. The study will also confirm that there is no bleeding concern with&#xD;
      the use of Protein C concentrates.The study drug will be administered in the Intensive Care&#xD;
      Unit for 72 hours and the patients observed till ICU discharge. Telephone followup will be&#xD;
      performed at 30 days and at one year.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite endpoint of number of participant with mortality and/or prolonged ICU stay</measure>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Protein C concentrate</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>Protein C concentrate</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Protein C concentrate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  At least one of the following 3 criteria:&#xD;
&#xD;
               -  venous-venous extra corporeal membrane oxygenation (ECMO) for septic adult&#xD;
                  respiratory distress syndrome (ARDS)&#xD;
&#xD;
               -  septic disseminated intravascular coagulopathy (DIC)&#xD;
&#xD;
               -  sepsis induced organ dysfunction associated with a clinical assessment of high&#xD;
                  risk of death&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous unusual response to PC or any of their components (murine proteins and&#xD;
             heparin)&#xD;
&#xD;
          -  PC administration or inclusion in other randomized protocols in the previous 30 days&#xD;
&#xD;
          -  Do not resuscitate orders&#xD;
&#xD;
          -  Refractory cardiogenic shock&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ospedale San Raffaele di Milano, Italy</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>July 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>December 14, 2015</last_update_submitted>
  <last_update_submitted_qc>December 14, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 15, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Università Vita-Salute San Raffaele</investigator_affiliation>
    <investigator_full_name>Giovanni Landoni</investigator_full_name>
    <investigator_title>Head of Research, Department of Anesthesiology and Intensive Care</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Protein C</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/NCT01705808
org study id: OSR/40/04/12
nct id: NCT01705808
lead sponsor: 
Severe sepsis and septic shock are life threatening medical emergencies and are among the
      most significant challenges in critical care. Case reports and case series suggest that
      plasma-derived protein C concentrate may improve the outcome of patients with acquired
      protein C deficiency. Evidence has accumulated on the clinical relevance of the PC pathway in
      modulating overwhelming inflammation and preventing coagulation derangements, two key
      mediators of organ damage, and thus of mortality and morbidity, in sepsis. The experience
      collected through these studies shows that PC is safe, in that it is not associated with
      bleeding or severe allergic complications,and possibly useful, at least to improve the
      coagulation abnormalities brought about by sepsis. Unfortunately, however, all we know comes
      from case series or case reports or an underpowered randomized controlled study. A randomized
      clinical trial, adequately powered for mortality or clinically relevant outcome, is necessary
      to confirm PC efficacy.The aim of this study is to demonstrate that Protein C zymogen has
      clinically relevant implications in terms of reduction of thromboembolic events, 30 days
      mortality, length of intensive care and hospital stay, time on mechanical ventilation, length
      of ICU and hospital stay. The study will also confirm that there is no bleeding concern with
      the use of Protein C concentrates.The study drug will be administered in the Intensive Care
      Unit for 72 hours and the patients observed till ICU discharge. Telephone followup will be
      performed at 30 days and at one year.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Composite endpoint of number of participant with mortality and/or prolonged ICU stay
arm group label: Protein C concentrate
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Protein C concentrate
arm group label: Placebo
arm group label: Protein C concentrate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Università Vita-Salute San Raffaele
investigator full name: Giovanni Landoni
investigator title: Head of Research, Department of Anesthesiology and Intensive Care
mesh term: Critical Illness
mesh term: Protein C