<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/NCT03788460</url>
  </required_header>
  <id_info>
    <org_study_id>0062-18-LND</org_study_id>
    <nct_id>NCT03788460</nct_id>
  </id_info>
  <brief_title>Correlation Between PT and INR to Factor 7</brief_title>
  <official_title>A Retro-prospective Pediatric Data Collection Study of the Correlation Between PT and the Level of Coagulant Factor VII</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laniado Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laniado Hospital</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>
      The purpose of our study:&#xD;
&#xD;
      Given the large number of coagulability tests done before a number of surgeries, specially&#xD;
      otolaryngology procedures, such as tonsillectomy and adenoidectomy, as well as a part of&#xD;
      epistaxis workup, prothrombin time (PT) and partial thromboplastin time (PTT) were checked,&#xD;
      and it was found that in some people there is an isolated elongated PT, a low level of factor&#xD;
      VII was found in these people.&#xD;
&#xD;
      The purpose of the current study is to find a correlation between the value of PT\INR and the&#xD;
      level of factor VII, we tried to do so by a retro-prospective study on patients known to have&#xD;
      a factor VII deficiency at Laniado hospital, such a correlation could make both the diagnosis&#xD;
      and the management of people with factor VII deficiency easier and more accessible.&#xD;
&#xD;
      The study levels:&#xD;
&#xD;
        1. Data collection : On the children's population who are known for their lack of Factor&#xD;
           VII, we will check PT levels, we will concentrate the data in the table, along with&#xD;
           personal information such as age and gender&#xD;
&#xD;
        2. Data Processing : We will try to conduct a statistical relationship between the PT&#xD;
           values and Factor VII levels, to look for statistical significance, we will try to find&#xD;
           a model for predicting the level of factor VII based on PT&#xD;
&#xD;
      Number of participants:&#xD;
&#xD;
      60 participants&#xD;
&#xD;
      Ages of participants:&#xD;
&#xD;
      0-18 years old&#xD;
&#xD;
      Gender of participants:&#xD;
&#xD;
      Both sexes&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
        1. A participant who is 0-18 years old&#xD;
&#xD;
        2. A participant who is, except for bleeding tendency, healthy in general&#xD;
&#xD;
        3. A participant who has elongated PT&#xD;
&#xD;
        4. A participant who has normal PTT&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        1. Background disease&#xD;
&#xD;
        2. Use of medications&#xD;
&#xD;
        3. Use of anti coagulation drugs&#xD;
&#xD;
      The duration of the study :&#xD;
&#xD;
      The study is of a retrospective type, we already have a number of subjects, we need more as&#xD;
      to reach statistical significance, so the expectation is two to three months&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Factor VII is one of the main components of the coagulation process. It belongs to the serine&#xD;
      proteases and it dependents on vitamin K in order to function. Its primary function is to&#xD;
      initiate the clotting process itself, along with tissue factor: Following a vascular&#xD;
      endothelial injury, there is a response of vasoconstriction, the blood flow in contact with&#xD;
      the subendothelial matrix, at that time, TF, a protein in the same matrix, binds to and&#xD;
      activates the VII coagulation factor, then, FVIIa-TF complex begins the coagulation cascade,&#xD;
      at the end of that cascade, fibrin is formed.&#xD;
&#xD;
      The factor VII gene is located on the long arm of chromosome 13, sized 12 kD, contains 12&#xD;
      axons that encode a protein composed of 406 amino acids, it's located at a distance of 2.8 kD&#xD;
      from the gene of factor X.&#xD;
&#xD;
      More than 120 mutations have been found in factor VII gene to date, the association between&#xD;
      genotype and phenotypes is unclear in most cases however. Seligsohn and his colleagues&#xD;
      described one of the mutations in Factor VII, 5-Ser339Phe, which was found in three Tunisian&#xD;
      families and caused a tendency to bleed through a mechanism of reduced factor X activation.&#xD;
&#xD;
      When it comes to Factor VII deficiency, the missing is never hermetic as such condition is&#xD;
      not compatible with life as seen from work on knockout mice. Partially missing factor VII is&#xD;
      the most common of all rare coagulation problems. Clinically, these are usually epistaxis,&#xD;
      easy bruising, gum bleeding, muscle hematoma, hamarhtrosis, hematuria, postoperative&#xD;
      bleeding, although there may also be conditions of life threatening blood in the nervous&#xD;
      system and in the gastrointestinal tract. Except for increased menstruation that occurs in&#xD;
      about 70% of the women with factor VII deficiency, there is no gender difference in symptoms.&#xD;
&#xD;
      Suspicion of Factor VII deficiency is usually done in the course of screening in family&#xD;
      members with a known deficiency or on tests following an episode of bleeding, such as&#xD;
      epistaxis or surgery in areas with a tendency to bleed (nose, throat or teeth) .&#xD;
&#xD;
      An abnormal PT test indicates a lack of factor VII. An elongated PTT test can suggest&#xD;
      hemophilia A and B (missing factors VIII and IX, respectively), lack of factor XI, incomplete&#xD;
      factor XII or von disease willebrand / VWF . The extension of PT also implies a deficiency in&#xD;
      the factors X, V, II and fibrinogen, and the result is represented by a percentage relative&#xD;
      to normal people.&#xD;
&#xD;
      The diagnosis of Factor VII deficiency is laboratory. The initial laboratory tests are PT,&#xD;
      aPTT and platelet count, followed by a FVII coagulant activity test for prolonged PT states.&#xD;
      In order to confirm the result, the FVII assay is performed again&#xD;
&#xD;
      Prothrombin time is typically analyzed by a laboratory technologist on an automated&#xD;
      instrument at 37 °C. Blood is drawn into a test tube containing liquid sodium citrate, which&#xD;
      acts as an anticoagulant by binding the calcium in a sample. The blood is mixed, then&#xD;
      centrifuged to separate blood cells from plasma (as prothrombin time is most commonly&#xD;
      measured using blood plasma). A sample of the plasma is extracted from the test tube and&#xD;
      placed into a measuring test tube Next an excess of calcium is added to the test tube,&#xD;
      thereby reversing the effects of citrate and enabling the blood to clot again. Finally, in&#xD;
      order to activate the extrinsic / tissue factor clotting cascade pathway, tissue factor is&#xD;
      added and the time the sample takes to clot is measured optically. The prothrombin ratio&#xD;
      (INR) is the prothrombin time for a patient sample divided by the result for control plasma.&#xD;
&#xD;
      There are two types of Factor VII deficiency. The first is a quantitative with both a lack of&#xD;
      FVII coagulant activity and with a low level of FVII antigen, the second one is qualitative&#xD;
      with a low FVII coagulant activity but a normal level of FVII antigen. In fact, the&#xD;
      examination of the antigen distinguishes between these two missing types, but does not&#xD;
      predict the tendency to bleed, and it is not recommended to diagnose Factor VII deficiency on&#xD;
      the basis of the antigen test. However, for known patients receiving a recombinant factor it&#xD;
      can be useful.&#xD;
&#xD;
      There are no clear guidelines for the treatment of hereditary deficiency VII. Recombinant&#xD;
      factor VII is a choice in many cases for both children and adults, but there are other&#xD;
      treatment options as discussed in our study.&#xD;
&#xD;
      The purpose of the current study is to find a correlation between the value of PT\INR and the&#xD;
      level of factor VII, we tried to do so by a retro-prospective study on patients known to have&#xD;
      a factor VII deficiency at Laniado hospital, such a correlation could make both the diagnosis&#xD;
      and the management of people with factor VII deficiency easier and more accessible.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 7, 2019</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">January 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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between PT, INR and the level of coagulant factor VII</measure>
    <time_frame>Study completion within 2 years</time_frame>
    <description>correlation between PT / INR value and percent of factor VII through a retro-prospective study of patients who are known to have factor VII deficiency. This correlation is expected to facilitate diagnostic and monitoring procedures for patients with factor VII deficiency. The clinical value of this study is to facilitate diagnosis and treatment in patients with Factor VII defiency.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Epistaxis</condition>
  <condition>ENT Disorder</condition>
  <arm_group>
    <arm_group_label>childrens population with lack of Factor VI</arm_group_label>
    <description>We will check PT levels, we will concentrate the data in the table, along with personal information such as age and gender.&#xD;
We will try to conduct a statistical relationship between the PT values and Factor VII levels, to look for statistical significance, we will try to find a model for predicting the level of factor VII based on PT</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>no intervention</intervention_name>
    <description>no intervention</description>
    <arm_group_label>childrens population with lack of Factor VI</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Children with known factor VII deficiency&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Elongated PT value; Normal PTT value;&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Background medical conditions; Taking anticoagulants; Taking chronic medications;&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Nechama Sharon, MD</last_name>
    <phone>+972-9-8604738</phone>
    <email>nsharon@laniado.org.il</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Moshe Yana</last_name>
    <phone>+972-9-8604717</phone>
    <email>myana@laniado.org.il</email>
  </overall_contact_backup>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 25, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 27, 2018</study_first_posted>
  <last_update_submitted>December 25, 2018</last_update_submitted>
  <last_update_submitted_qc>December 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Laniado Hospital</investigator_affiliation>
    <investigator_full_name>Dr. Nechama Sharon</investigator_full_name>
    <investigator_title>Head, Pediatric hemato-oncology unit</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epistaxis</mesh_term>
  </condition_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/NCT03788460
org study id: 0062-18-LND
nct id: NCT03788460
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of our study:

      Given the large number of coagulability tests done before a number of surgeries, specially
      otolaryngology procedures, such as tonsillectomy and adenoidectomy, as well as a part of
      epistaxis workup, prothrombin time (PT) and partial thromboplastin time (PTT) were checked,
      and it was found that in some people there is an isolated elongated PT, a low level of factor
      VII was found in these people.

      The purpose of the current study is to find a correlation between the value of PT\INR and the
      level of factor VII, we tried to do so by a retro-prospective study on patients known to have
      a factor VII deficiency at Laniado hospital, such a correlation could make both the diagnosis
      and the management of people with factor VII deficiency easier and more accessible.

      The study levels:

        1. Data collection : On the children's population who are known for their lack of Factor
           VII, we will check PT levels, we will concentrate the data in the table, along with
           personal information such as age and gender

        2. Data Processing : We will try to conduct a statistical relationship between the PT
           values and Factor VII levels, to look for statistical significance, we will try to find
           a model for predicting the level of factor VII based on PT

      Number of participants:

      60 participants

      Ages of participants:

      0-18 years old

      Gender of participants:

      Both sexes

      Inclusion criteria:

        1. A participant who is 0-18 years old

        2. A participant who is, except for bleeding tendency, healthy in general

        3. A participant who has elongated PT

        4. A participant who has normal PTT

      Exclusion criteria:

        1. Background disease

        2. Use of medications

        3. Use of anti coagulation drugs

      The duration of the study :

      The study is of a retrospective type, we already have a number of subjects, we need more as
      to reach statistical significance, so the expectation is two to three months
Factor VII is one of the main components of the coagulation process. It belongs to the serine
      proteases and it dependents on vitamin K in order to function. Its primary function is to
      initiate the clotting process itself, along with tissue factor: Following a vascular
      endothelial injury, there is a response of vasoconstriction, the blood flow in contact with
      the subendothelial matrix, at that time, TF, a protein in the same matrix, binds to and
      activates the VII coagulation factor, then, FVIIa-TF complex begins the coagulation cascade,
      at the end of that cascade, fibrin is formed.

      The factor VII gene is located on the long arm of chromosome 13, sized 12 kD, contains 12
      axons that encode a protein composed of 406 amino acids, it's located at a distance of 2.8 kD
      from the gene of factor X.

      More than 120 mutations have been found in factor VII gene to date, the association between
      genotype and phenotypes is unclear in most cases however. Seligsohn and his colleagues
      described one of the mutations in Factor VII, 5-Ser339Phe, which was found in three Tunisian
      families and caused a tendency to bleed through a mechanism of reduced factor X activation.

      When it comes to Factor VII deficiency, the missing is never hermetic as such condition is
      not compatible with life as seen from work on knockout mice. Partially missing factor VII is
      the most common of all rare coagulation problems. Clinically, these are usually epistaxis,
      easy bruising, gum bleeding, muscle hematoma, hamarhtrosis, hematuria, postoperative
      bleeding, although there may also be conditions of life threatening blood in the nervous
      system and in the gastrointestinal tract. Except for increased menstruation that occurs in
      about 70% of the women with factor VII deficiency, there is no gender difference in symptoms.

      Suspicion of Factor VII deficiency is usually done in the course of screening in family
      members with a known deficiency or on tests following an episode of bleeding, such as
      epistaxis or surgery in areas with a tendency to bleed (nose, throat or teeth) .

      An abnormal PT test indicates a lack of factor VII. An elongated PTT test can suggest
      hemophilia A and B (missing factors VIII and IX, respectively), lack of factor XI, incomplete
      factor XII or von disease willebrand / VWF . The extension of PT also implies a deficiency in
      the factors X, V, II and fibrinogen, and the result is represented by a percentage relative
      to normal people.

      The diagnosis of Factor VII deficiency is laboratory. The initial laboratory tests are PT,
      aPTT and platelet count, followed by a FVII coagulant activity test for prolonged PT states.
      In order to confirm the result, the FVII assay is performed again

      Prothrombin time is typically analyzed by a laboratory technologist on an automated
      instrument at 37 °C. Blood is drawn into a test tube containing liquid sodium citrate, which
      acts as an anticoagulant by binding the calcium in a sample. The blood is mixed, then
      centrifuged to separate blood cells from plasma (as prothrombin time is most commonly
      measured using blood plasma). A sample of the plasma is extracted from the test tube and
      placed into a measuring test tube Next an excess of calcium is added to the test tube,
      thereby reversing the effects of citrate and enabling the blood to clot again. Finally, in
      order to activate the extrinsic / tissue factor clotting cascade pathway, tissue factor is
      added and the time the sample takes to clot is measured optically. The prothrombin ratio
      (INR) is the prothrombin time for a patient sample divided by the result for control plasma.

      There are two types of Factor VII deficiency. The first is a quantitative with both a lack of
      FVII coagulant activity and with a low level of FVII antigen, the second one is qualitative
      with a low FVII coagulant activity but a normal level of FVII antigen. In fact, the
      examination of the antigen distinguishes between these two missing types, but does not
      predict the tendency to bleed, and it is not recommended to diagnose Factor VII deficiency on
      the basis of the antigen test. However, for known patients receiving a recombinant factor it
      can be useful.

      There are no clear guidelines for the treatment of hereditary deficiency VII. Recombinant
      factor VII is a choice in many cases for both children and adults, but there are other
      treatment options as discussed in our study.

      The purpose of the current study is to find a correlation between the value of PT\INR and the
      level of factor VII, we tried to do so by a retro-prospective study on patients known to have
      a factor VII deficiency at Laniado hospital, such a correlation could make both the diagnosis
      and the management of people with factor VII deficiency easier and more accessible.
observational model: Cohort
time perspective: Other
measure: Correlation between PT, INR and the level of coagulant factor VII
time frame: Study completion within 2 years
description: correlation between PT / INR value and percent of factor VII through a retro-prospective study of patients who are known to have factor VII deficiency. This correlation is expected to facilitate diagnostic and monitoring procedures for patients with factor VII deficiency. The clinical value of this study is to facilitate diagnosis and treatment in patients with Factor VII defiency.
arm group label: childrens population with lack of Factor VI
description: We will check PT levels, we will concentrate the data in the table, along with personal information such as age and gender.
We will try to conduct a statistical relationship between the PT values and Factor VII levels, to look for statistical significance, we will try to find a model for predicting the level of factor VII based on PT
intervention type: Other
intervention name: no intervention
description: no intervention
arm group label: childrens population with lack of Factor VI
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
last name: Nechama Sharon, MD
phone: +972-9-8604738
email: nsharon@laniado.org.il
last name: Moshe Yana
phone: +972-9-8604717
email: myana@laniado.org.il
responsible party type: Principal Investigator
investigator affiliation: Laniado Hospital
investigator full name: Dr. Nechama Sharon
investigator title: Head, Pediatric hemato-oncology unit
mesh term: Epistaxis
sharing ipd: No