<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/NCT03782025</url>
  </required_header>
  <id_info>
    <org_study_id>VITAKOAG</org_study_id>
    <nct_id>NCT03782025</nct_id>
  </id_info>
  <brief_title>Effect of Vitamin K in Critically Ill Patients</brief_title>
  <acronym>VITAKOAG</acronym>
  <official_title>Effect of Vitamin K in Critically Ill Patients With Spontaneously Increased Pro-thrombin Time Measured With Routine Coagulation Tests and Advanced Coagulation- and Vitamin K-assays</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Skane</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Region Skane</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Critically ill patients with spontaneously prolonged pro-thrombin time, where administration&#xD;
      of intravenous administration of phytomenadione (vitamin K) has been ordered by the treating&#xD;
      physician will be identified. After signed informed consent baseline samples will be&#xD;
      collected. Phytomenadione will be given and 24 hours after administration new blood samples&#xD;
      will be collected. Several different advanced coagulation and vitamin K-assays will be&#xD;
      performed before and 24 hours after vitamin K administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin K-deficiency is common in the peri-operative and intensive care setting. It is often&#xD;
      seen in patients with prolonged prothrombin complex (PK-INR). A prolonged (PK-INR) is&#xD;
      sometimes treated with intravenous vitamin K, even in non-warfarin treated or non-liver&#xD;
      failure patients. Despite the development of this practice the knowledge about how&#xD;
      intravenously given vitamin K affects routine coagulation status and other advanced&#xD;
      laboratory coagulations assays is rare.&#xD;
&#xD;
      The aim of this study is to investigate the effects of intravenously administered vitamin K&#xD;
      on routine coagulation status and on advanced coagulation and vitamin K-assays in&#xD;
      post-operative- and critically ill patients with prolonged PK-INR.&#xD;
&#xD;
      Patients with spontaneously prolonged PK-INR are routinely given intravenous vitamin K but it&#xD;
      is largely unknown how this procedure affects the included coagulation assays. This research&#xD;
      project may contribute to increased knowledge concerning effects of intravenously given&#xD;
      vitamin K in critical ill patients with spontaneous coagulopathies. Since spontaneous&#xD;
      coagulopathy is frequently occurring in critically ill and postoperative patients due to&#xD;
      various underlying conditions and current evidence for vitamin K administration is based on&#xD;
      scarce evidence more research in this area is motivated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 13, 2019</start_date>
  <completion_date type="Actual">March 20, 2020</completion_date>
  <primary_completion_date type="Actual">March 20, 2020</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>Change in prothrombin complex (PK-INR)</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
    <description>Prothrombin complex (PK-INR) with Owren and Quick reagents</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in concentration of coagulation factors II, VII, IX and X in plasma</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in concentration of PIVKA-II in plasma</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
    <description>Protein Induced by Vitamin K Absence or antagonism for factor II (PIVKA-II)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in concentration of protein C and S in plasma</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in concentration of dp-ucMGP in plasma</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
    <description>Dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in thrombin generation assay in plasma</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in thromboelastometry assay in whole blood</measure>
    <time_frame>Before and 24 hours after given phytomenadione</time_frame>
    <description>Thromboelastometry using ROTEM with tissue factor activation (EXTEM reagent)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">52</enrollment>
  <condition>Coagulation Factor Deficiency</condition>
  <condition>Coagulopathy, Consumption</condition>
  <condition>Vitamin K Deficiency</condition>
  <arm_group>
    <arm_group_label>Patients with increased PK-INR</arm_group_label>
    <description>Critically ill patients with spontaneously increased prothrombin complex (PK-INR) who are given phytomenadione intravenously at the discretion of the treating physician</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Phytomenadione</intervention_name>
    <description>Blood samples will be taken before and after intravenously prescribed phytomenadione is given. Phytomenadione will be given independently of this study.</description>
    <arm_group_label>Patients with increased PK-INR</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be centrifuged and stored in -80 degrees C in anticipation of batch&#xD;
      analysis of coagulation factor- and vitamin K-analyses. There will be no DNA analysis. All&#xD;
      blood samples will be destroyed after the mentioned analyses.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Critically ill patients at the postoperative care unit or at the intensive care unit with a&#xD;
        prothrombin complex (PK-INR) &gt; 1.2 during office hours who are ordered parenteral&#xD;
        phytomenadione 10 mg will be eligible for inclusion&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Critically ill patients at the postoperative care unit or at the intensive care unit&#xD;
             with a prothrombin complex (PK-INR) &gt; 1.2 during office hours who are ordered&#xD;
             parenteral phytomenadione 10 mg will be eligible for inclusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Warfarin treatment&#xD;
&#xD;
          -  Treatment with novel oral anticoagulants&#xD;
&#xD;
          -  Hepatocellular carcinoma&#xD;
&#xD;
          -  Liver resection within 6 months&#xD;
&#xD;
          -  Known pre-existing coagulopathy&#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>Thomas Kander, Ass. Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Skane University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Intensive and perioperative care. Skåne University Hospital. Lund</name>
      <address>
        <city>Lund</city>
        <state>Skåne</state>
        <zip>22185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skåne University Hospital</name>
      <address>
        <city>Lund</city>
        <state>Skåne</state>
        <zip>22185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>March 16, 2021</last_update_submitted>
  <last_update_submitted_qc>March 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Region Skane</investigator_affiliation>
    <investigator_full_name>Thomas Kander</investigator_full_name>
    <investigator_title>Consultant</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin K Deficiency</mesh_term>
    <mesh_term>Disseminated Intravascular Coagulation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin K 1</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03782025
org study id: VITAKOAG
nct id: NCT03782025
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Critically ill patients with spontaneously prolonged pro-thrombin time, where administration
      of intravenous administration of phytomenadione (vitamin K) has been ordered by the treating
      physician will be identified. After signed informed consent baseline samples will be
      collected. Phytomenadione will be given and 24 hours after administration new blood samples
      will be collected. Several different advanced coagulation and vitamin K-assays will be
      performed before and 24 hours after vitamin K administration.
Vitamin K-deficiency is common in the peri-operative and intensive care setting. It is often
      seen in patients with prolonged prothrombin complex (PK-INR). A prolonged (PK-INR) is
      sometimes treated with intravenous vitamin K, even in non-warfarin treated or non-liver
      failure patients. Despite the development of this practice the knowledge about how
      intravenously given vitamin K affects routine coagulation status and other advanced
      laboratory coagulations assays is rare.

      The aim of this study is to investigate the effects of intravenously administered vitamin K
      on routine coagulation status and on advanced coagulation and vitamin K-assays in
      post-operative- and critically ill patients with prolonged PK-INR.

      Patients with spontaneously prolonged PK-INR are routinely given intravenous vitamin K but it
      is largely unknown how this procedure affects the included coagulation assays. This research
      project may contribute to increased knowledge concerning effects of intravenously given
      vitamin K in critical ill patients with spontaneous coagulopathies. Since spontaneous
      coagulopathy is frequently occurring in critically ill and postoperative patients due to
      various underlying conditions and current evidence for vitamin K administration is based on
      scarce evidence more research in this area is motivated.
observational model: Cohort
time perspective: Prospective
measure: Change in prothrombin complex (PK-INR)
time frame: Before and 24 hours after given phytomenadione
description: Prothrombin complex (PK-INR) with Owren and Quick reagents
measure: Change in concentration of coagulation factors II, VII, IX and X in plasma
time frame: Before and 24 hours after given phytomenadione
measure: Change in concentration of PIVKA-II in plasma
time frame: Before and 24 hours after given phytomenadione
description: Protein Induced by Vitamin K Absence or antagonism for factor II (PIVKA-II)
measure: Change in concentration of protein C and S in plasma
time frame: Before and 24 hours after given phytomenadione
measure: Change in concentration of dp-ucMGP in plasma
time frame: Before and 24 hours after given phytomenadione
description: Dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP)
measure: Change in thrombin generation assay in plasma
time frame: Before and 24 hours after given phytomenadione
measure: Change in thromboelastometry assay in whole blood
time frame: Before and 24 hours after given phytomenadione
description: Thromboelastometry using ROTEM with tissue factor activation (EXTEM reagent)
arm group label: Patients with increased PK-INR
description: Critically ill patients with spontaneously increased prothrombin complex (PK-INR) who are given phytomenadione intravenously at the discretion of the treating physician
intervention type: Drug
intervention name: Phytomenadione
description: Blood samples will be taken before and after intravenously prescribed phytomenadione is given. Phytomenadione will be given independently of this study.
arm group label: Patients with increased PK-INR
Blood samples will be centrifuged and stored in -80 degrees C in anticipation of batch
      analysis of coagulation factor- and vitamin K-analyses. There will be no DNA analysis. All
      blood samples will be destroyed after the mentioned analyses.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Kander, Ass. Prof.
role: Principal Investigator
affiliation: Skane University Hospital
facility: 
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Region Skane
investigator full name: Thomas Kander
investigator title: Consultant
mesh term: Vitamin K Deficiency
mesh term: Disseminated Intravascular Coagulation
mesh term: Vitamin K 1
sharing ipd: No