<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/NCT01701947</url>
  </required_header>
  <id_info>
    <org_study_id>HM11-1102</org_study_id>
    <nct_id>NCT01701947</nct_id>
  </id_info>
  <brief_title>HEMOLEVEN® Expanded Access Program Prevention of Surgical/Postpartum Hemorrhage Severe Inherited Factor XI Deficiency</brief_title>
  <acronym>EAP</acronym>
  <official_title>HEMOLEVEN® Expanded Access Program for Prevention of Surgical and Postpartum Hemorrhage in Patients With Severe Inherited Factor XI Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laboratoire français de Fractionnement et de Biotechnologies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laboratoire français de Fractionnement et de Biotechnologies</source>
  <brief_summary>
    <textblock>
      The objective of the Expanded Access Program is to provide HEMOLEVEN, a replacement&#xD;
      coagulation factor XI, to patients with severe inherited factor XI deficiency where, in the&#xD;
      opinion of the treating physician, the benefits of administering selectively the missing&#xD;
      factor outweigh the potential risks associated with the administration of fresh-frozen&#xD;
      plasma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many patients are asymptomatic until hemostatically challenged by surgery or trauma; so, the&#xD;
      diagnosis is often made in late childhood or early adulthood but always after full liver&#xD;
      maturation (i.e. 6 months) as reported by Andrew et al.&#xD;
&#xD;
      Spontaneous bleeding is rare, except menorrhagia, and bleeding occurs mainly after surgery or&#xD;
      injury. Bleeding is observed mainly in surgical sites with high fibrinolytic activity such as&#xD;
      mouth, nose, or the genitourinary tract.&#xD;
&#xD;
      Pregnancy, labor and delivery can also be challenging for women with FXI deficiency. In 1999&#xD;
      a study published in the American Journal of Hematology revealed that FXI levels are&#xD;
      inconsistent during pregnancy. The incidence of postpartum hemorrhage is increased in women&#xD;
      with factor XI deficiency. The incidence is 16% for the primary postpartum hemorrhage in FXI&#xD;
      patients, compared with 5% in the general population. Moreover, the incidence is 24% for the&#xD;
      secondary postpartum hemorrhage in comparison with that in the general obstetric population&#xD;
      (0.7%). The authors recommend that FXI levels be obtained during the initial visit and&#xD;
      monitored during the woman's third trimester. For all of these reasons it is important for&#xD;
      women who suspect they might have a FXI deficiency to be tested and diagnosed before&#xD;
      pregnancy.&#xD;
&#xD;
      Severe factor XI deficiency is defined by levels of &lt;0.20 IU/mL. Such individuals have a high&#xD;
      probability of post-operative hemorrhage. Individuals with levels between 0.20 IU/mL and the&#xD;
      lower limit of the normal range, generally 0.65-0.80 IU/mL, are generally classified as&#xD;
      having partial or mild deficiency with a lower risk of post-operative bleeding. Partial&#xD;
      deficiency is being increasingly recognized following pre-operative tests or as a result of&#xD;
      family screening. Thus partial factor XI deficiency is often diagnosed in asymptomatic&#xD;
      individuals, creating management dilemmas because of the unpredictability of the bleeding&#xD;
      risk. To differentiate an isolated or combined bleeding disorder in a patient with factor XI&#xD;
      deficiency, other causes of bleeding should be investigated and excluded (e.g. von Willebrand&#xD;
      disease, platelet disorders).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>No longer available</overall_status>
  <study_type>Expanded Access</study_type>
  <condition>Wound; Rupture, Surgery, Cesarean Section</condition>
  <condition>Postpartum Hemorrhage</condition>
  <condition>Surgery</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Hemoleven</intervention_name>
    <description>Replacement therapy</description>
    <other_name>Human Coagulation Factor XI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Severe inherited factor XI deficiency (FXI:C &lt; 0.20 IU/mL i.e. &lt;20 %)&#xD;
&#xD;
          2. Patient older than 6 months old and weight at least 8 kg&#xD;
&#xD;
          3. Known personal bleeding history&#xD;
&#xD;
          4. Patient requiring FXI replacement therapy when oral antifibrinolytic agents alone or&#xD;
             other means are ineffective or are contraindicated&#xD;
&#xD;
          5. Scheduled to undergo an elective surgical procedure (including caesarean section) for&#xD;
             which the patient requires hemostasis prophylaxis, which in the case of caesarean&#xD;
             section is due to a history of postpartum bleeding, OR vaginal delivery for which the&#xD;
             patient requires hemostasis prophylaxis due to a history of postpartum hemorrhage&#xD;
&#xD;
          6. Patient/guardian provides signed and dated Informed Consent for 'HEMOLEVEN Expanded&#xD;
             Access Program' prior to entry into the program&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Personal history of thromboembolic events&#xD;
&#xD;
          2. Underlying cardiopulmonary disease of NYHA Class III or greater&#xD;
&#xD;
          3. History of severe reaction to any component of HEMOLEVEN notably to heparin or to its&#xD;
             derivatives,including LMWH. Past history of serious type II heparin-induced&#xD;
             thrombocytopenia (HIT)&#xD;
&#xD;
          4. Presence of antibody to FXI in the past or currently&#xD;
&#xD;
          5. Presence of any other condition that could contraindicate treatment with factor XI&#xD;
             concentrate or lead the Physician/Investigator to believe treatment would not be in&#xD;
             the best interest of the patient&#xD;
&#xD;
          6. Positive, confirmed pregnancy test for patients undergoing elective surgery (not&#xD;
             applicable for caesarean section and prevention in vaginal delivery)&#xD;
&#xD;
          7. Lactating woman.&#xD;
&#xD;
        Of the seven exclusion criteria, the first four are included as a precautionary safety&#xD;
        measure; the fifth is included to avoid a lack of efficacy.&#xD;
&#xD;
        The two last criteria are included to minimize confounding influences on the evaluation of&#xD;
        patient safety. Oral contraception is not mandatory as a pregnancy test is scheduled at&#xD;
        inclusion visit and before surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Anne T Neff, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center - Hemostasis &amp; Thrombosis Ctr</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-5505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2013</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>August 22, 2013</last_update_submitted>
  <last_update_submitted_qc>August 22, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 23, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Factor XI deficiency</keyword>
  <keyword>EAP</keyword>
  <keyword>postpartum hemorrhage</keyword>
  <keyword>surgery</keyword>
  <keyword>delivery</keyword>
  <keyword>Child birth</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postpartum Hemorrhage</mesh_term>
    <mesh_term>Factor XI Deficiency</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Rupture</mesh_term>
  </condition_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/NCT01701947
org study id: HM11-1102
nct id: NCT01701947
lead sponsor: 
The objective of the Expanded Access Program is to provide HEMOLEVEN, a replacement
      coagulation factor XI, to patients with severe inherited factor XI deficiency where, in the
      opinion of the treating physician, the benefits of administering selectively the missing
      factor outweigh the potential risks associated with the administration of fresh-frozen
      plasma.
Many patients are asymptomatic until hemostatically challenged by surgery or trauma; so, the
      diagnosis is often made in late childhood or early adulthood but always after full liver
      maturation (i.e. 6 months) as reported by Andrew et al.

      Spontaneous bleeding is rare, except menorrhagia, and bleeding occurs mainly after surgery or
      injury. Bleeding is observed mainly in surgical sites with high fibrinolytic activity such as
      mouth, nose, or the genitourinary tract.

      Pregnancy, labor and delivery can also be challenging for women with FXI deficiency. In 1999
      a study published in the American Journal of Hematology revealed that FXI levels are
      inconsistent during pregnancy. The incidence of postpartum hemorrhage is increased in women
      with factor XI deficiency. The incidence is 16% for the primary postpartum hemorrhage in FXI
      patients, compared with 5% in the general population. Moreover, the incidence is 24% for the
      secondary postpartum hemorrhage in comparison with that in the general obstetric population
      (0.7%). The authors recommend that FXI levels be obtained during the initial visit and
      monitored during the woman's third trimester. For all of these reasons it is important for
      women who suspect they might have a FXI deficiency to be tested and diagnosed before
      pregnancy.

      Severe factor XI deficiency is defined by levels of <0.20 IU/mL. Such individuals have a high
      probability of post-operative hemorrhage. Individuals with levels between 0.20 IU/mL and the
      lower limit of the normal range, generally 0.65-0.80 IU/mL, are generally classified as
      having partial or mild deficiency with a lower risk of post-operative bleeding. Partial
      deficiency is being increasingly recognized following pre-operative tests or as a result of
      family screening. Thus partial factor XI deficiency is often diagnosed in asymptomatic
      individuals, creating management dilemmas because of the unpredictability of the bleeding
      risk. To differentiate an isolated or combined bleeding disorder in a patient with factor XI
      deficiency, other causes of bleeding should be investigated and excluded (e.g. von Willebrand
      disease, platelet disorders).
intervention type: Biological
intervention name: Hemoleven
description: Replacement therapy
other name: Human Coagulation Factor XI
criteria: 
gender: All
minimum age: 6 Months
maximum age: N/A
last name: Anne T Neff, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Postpartum Hemorrhage
mesh term: Factor XI Deficiency
mesh term: Hemorrhage
mesh term: Rupture