<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/NCT01708239</url>
  </required_header>
  <id_info>
    <org_study_id>Geneva University Hospital</org_study_id>
    <nct_id>NCT01708239</nct_id>
  </id_info>
  <brief_title>Left Rule, D-Dimer Measurement and Complete Ultrasonography to Rule Out Deep Vein Thrombosis During Pregnancy.</brief_title>
  <official_title>Sequential Use of the LEFt Rule, D-dimer Measurement and Complete Ultrasonography to Rule Out Deep Vein Thrombosis During Pregnancy: a Prospective Outcome Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marc Righini</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Brest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Ottawa Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Geneva</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In pregnant women with suspected DVT, a sure diagnosis is mandatory. In non-pregnant&#xD;
      patients, sequential diagnostic strategies based on 1) the assessment of clinical&#xD;
      probability, 2) D-dimer measurement and 3) compression ultrasonography (CUS) have been well&#xD;
      validated.&#xD;
&#xD;
      Clinical probability assessment by clinical prediction rules (CPRs) is a crucial step in the&#xD;
      management of suspected DVT. However, the most commonly used CPR for DVT, the Wells' score,&#xD;
      has never been validated in pregnant women. Recently, the 'LEFt' clinical prediction rule was&#xD;
      derived and internally validated. A prospective validation of this rule is now warranted, and&#xD;
      we plan to use it in our prospective study.&#xD;
&#xD;
      The second step used in the diagnostic strategy including non-pregnant patients is D-dimer&#xD;
      measurement. The test has been widely validated in non-pregnant patients and, in association&#xD;
      with a non-high clinical probability, it allows to safely rule out DVT.&#xD;
&#xD;
      As D-dimer level raise steadily during pregnancy, the specificity of the test decreases and&#xD;
      it is less useful in pregnant women. Data from the literature clearly suggest that the usual&#xD;
      cut-off set a 500 ng/ml would safely rule out DVT in pregnant women [6]. As the usual cut-off&#xD;
      has never been prospectively validated in pregnant women with suspected DVT, we would like to&#xD;
      use it in our study.&#xD;
&#xD;
      Some studies suggested that complete CUS is safe to rule out DVT in pregnant women. However,&#xD;
      this test is not always available. Therefore, a strategy in which the association of clinical&#xD;
      probability assessment and D-dimer measurement would allow to safely rule out DVT in a&#xD;
      significant proportion of patients without performing a complete CUS, would be of great help&#xD;
      in everyday clinical practice and would probably be cost-effective.&#xD;
&#xD;
      Therefore, we plan a prospective study to assess the safety of a sequential diagnostic&#xD;
      strategy based on the assessment of clinical probability with the LEFt rule, D-dimer&#xD;
      measurement and complete CUS in pregnant women with suspected DVT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In pregnant women with suspected DVT, a sure diagnosis is mandatory. Indeed, false positive&#xD;
      tests lead to inappropriate anticoagulant treatment, which increases the risk of bleeding.&#xD;
      Conversely, false negative tests might lead to a life-threatening thromboembolic event. Thus,&#xD;
      accuracy of diagnostic methods used in pregnant women is crucial [1].&#xD;
&#xD;
      In non-pregnant patients, sequential diagnostic strategies based on 1) the assessment of&#xD;
      clinical probability, 2) D-dimer measurement and 3) compression ultrasonography (CUS) have&#xD;
      been widely validated [2, 3].&#xD;
&#xD;
      Clinical probability assessment by clinical prediction rules (CPRs) is a crucial step in the&#xD;
      management of suspected DVT. However, the most commonly used CPR for DVT, the Wells' score,&#xD;
      has never been validated in pregnant women [3]. Recently, the 'LEFt' clinical prediction rule&#xD;
      was derived and internally validated by Chan et al. among 194 pregnant women investigated for&#xD;
      suspected DVT[4]. This rule combines three variables: symptoms in the left leg (&quot;L&quot;), calf&#xD;
      circumference difference equal or greater than 2 centimeters (&quot;E&quot; for edema) and first&#xD;
      trimester presentation (&quot;Ft&quot;) [4].&#xD;
&#xD;
      We performed an external validation of this rule on a recently published prospective cohort&#xD;
      of pregnant patients with suspected DVT (submitted to JTH). This external validation showed&#xD;
      that a negative &quot;LEFt&quot; rule accurately identified pregnant women in whom the proportion of&#xD;
      confirmed DVT appears to be very low. A prospective validation of this rule is now warranted,&#xD;
      and we plan to use it in our prospective study.&#xD;
&#xD;
      The second step used in the diagnostic strategy including non-pregnant patients is D-dimer&#xD;
      measurement. The test has been widely validated in non-pregnant patients and, in association&#xD;
      with a non-high clinical probability, it allows to safely rule out DVT [5].&#xD;
&#xD;
      As D-dimer level raise steadily during pregnancy, the specificity of the test decreases and&#xD;
      it is less useful in pregnant women. A recent study suggested that the currently available&#xD;
      sensitive D-dimer assays that are used for the exclusion in symptomatic non-pregnant women&#xD;
      have the potential to exclude DVT in symptomatic pregnant women with the application of&#xD;
      higher cut-points [6]. Even if this data arises from a small study, it clearly suggests that&#xD;
      the usual cut-off set a 500 ng/ml would safely rule out DVT in pregnant women [6]. As the&#xD;
      usual cut-off has never been prospectively validated in pregnant women with suspected DVT, we&#xD;
      would like, as a first step, to use it in our study.&#xD;
&#xD;
      In pregnant patients, limited data is available on the use of complete compression&#xD;
      ultrasonography to rule out DVT. In a recent prospective management study, we included 226&#xD;
      pregnant and post-partum women with suspected lower limb DVT. We observed a 1.1% (95%&#xD;
      CI:0.3-4.0) three-month thromboembolic event rate in those left untreated on the basis of a&#xD;
      negative single complete CUS [7]. This result is in line with what was reported after a&#xD;
      normal phlebography, the gold standard test [8].&#xD;
&#xD;
      Even if complete CUS is safe to rule out DVT in pregnant women, current diagnostic strategies&#xD;
      for suspected DVT in non-pregnant patients rely on the use of clinical probability and&#xD;
      D-Dimer prior to leg veins imaging [5]. However, no management outcome study on the safety&#xD;
      and usefulness of D-Dimer to rule out DVT in pregnant women is available to date. Another&#xD;
      limitation of the strategies based on a single unique complete CUS, is that every woman has&#xD;
      to undergo complete CUS. However, this test is not always available. Therefore, a strategy in&#xD;
      which the association of clinical probability assessment and D-dimer measurement would allow&#xD;
      to safely rule out DVT in a significant proportion of patients without performing a complete&#xD;
      CUS, would be of great help in everyday clinical practice and would probably be&#xD;
      cost-effective.&#xD;
&#xD;
      Therefore, we plan a prospective study to assess the safety of a sequential diagnostic&#xD;
      strategy based on the assessment of clinical probability with the LEFt rule, D-dimer&#xD;
      measurement and complete CUS in pregnant women with suspected DVT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2019</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>The main outcome will be the number of thromboembolic recurrent events (DVT, PE, death attributable to venous thromboembolic disease) documented during the three-month follow-up in the patients left untreated on the basis of a normal diagnostic strategy.</measure>
    <time_frame>3 years</time_frame>
    <description>Rate of thromboembolic events after a normal diagnostic strategy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prospective evaluation of the diagnostic performances of the LEFt rule.</measure>
    <time_frame>3 years</time_frame>
    <description>Prospective validation of the LEFt rule.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prospective evaluation of D-dimer measurement to rule out DVT in pregnant women.</measure>
    <time_frame>3 years</time_frame>
    <description>Prospective evaluation of the diagnostic performances of D-dimer measurement in pregnant women with suspected DVT.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Pregnancy</condition>
  <condition>Deep Vein Thrombosis</condition>
  <arm_group>
    <arm_group_label>Pregnant women</arm_group_label>
    <description>Pregnant women with suspected DVT assessed by the LEFt rule, D-dimer measurement and complete ultrasonography.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Left rule, D-dimer measurement and complete ultrasonography in pregnant women.</intervention_name>
    <description>Diagnostic strategy based on the LEFt rule, D-dimer measurement and complete ultrasonography</description>
    <arm_group_label>Pregnant women</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women with suspected DVT&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Pregnant women with clinically suspected DVT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18&#xD;
&#xD;
          -  No available informed consent&#xD;
&#xD;
          -  Associated suspicion of pulmonary embolism&#xD;
&#xD;
          -  Ongoing anticoagulant treatment&#xD;
&#xD;
          -  Planned anticoagulant treatment at therapeutic dosage during pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grégoire Le Gal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ottawa Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Geneva University Hospital</name>
      <address>
        <city>Geneva</city>
        <zip>1205</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc Righini, MD</last_name>
      <phone>+41 22 372 92 94</phone>
      <email>marc.righini@hcuge.ch</email>
    </contact>
    <contact_backup>
      <last_name>Helia Robert-Ebadi, MD</last_name>
      <phone>+41 22 372 92 92</phone>
      <email>helia.robert-ebadi@hcuge.ch</email>
    </contact_backup>
    <investigator>
      <last_name>Marc Righini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>May 3, 2018</last_update_submitted>
  <last_update_submitted_qc>May 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Marc Righini</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Pregnancy</keyword>
  <keyword>Deep vein thrombosis</keyword>
  <keyword>Clinical probability</keyword>
  <keyword>D-Dimer</keyword>
  <keyword>Compression ultrasonography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrin fragment D</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/NCT01708239
org study id: Geneva University Hospital
nct id: NCT01708239
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
In pregnant women with suspected DVT, a sure diagnosis is mandatory. In non-pregnant
      patients, sequential diagnostic strategies based on 1) the assessment of clinical
      probability, 2) D-dimer measurement and 3) compression ultrasonography (CUS) have been well
      validated.

      Clinical probability assessment by clinical prediction rules (CPRs) is a crucial step in the
      management of suspected DVT. However, the most commonly used CPR for DVT, the Wells' score,
      has never been validated in pregnant women. Recently, the 'LEFt' clinical prediction rule was
      derived and internally validated. A prospective validation of this rule is now warranted, and
      we plan to use it in our prospective study.

      The second step used in the diagnostic strategy including non-pregnant patients is D-dimer
      measurement. The test has been widely validated in non-pregnant patients and, in association
      with a non-high clinical probability, it allows to safely rule out DVT.

      As D-dimer level raise steadily during pregnancy, the specificity of the test decreases and
      it is less useful in pregnant women. Data from the literature clearly suggest that the usual
      cut-off set a 500 ng/ml would safely rule out DVT in pregnant women [6]. As the usual cut-off
      has never been prospectively validated in pregnant women with suspected DVT, we would like to
      use it in our study.

      Some studies suggested that complete CUS is safe to rule out DVT in pregnant women. However,
      this test is not always available. Therefore, a strategy in which the association of clinical
      probability assessment and D-dimer measurement would allow to safely rule out DVT in a
      significant proportion of patients without performing a complete CUS, would be of great help
      in everyday clinical practice and would probably be cost-effective.

      Therefore, we plan a prospective study to assess the safety of a sequential diagnostic
      strategy based on the assessment of clinical probability with the LEFt rule, D-dimer
      measurement and complete CUS in pregnant women with suspected DVT.
In pregnant women with suspected DVT, a sure diagnosis is mandatory. Indeed, false positive
      tests lead to inappropriate anticoagulant treatment, which increases the risk of bleeding.
      Conversely, false negative tests might lead to a life-threatening thromboembolic event. Thus,
      accuracy of diagnostic methods used in pregnant women is crucial [1].

      In non-pregnant patients, sequential diagnostic strategies based on 1) the assessment of
      clinical probability, 2) D-dimer measurement and 3) compression ultrasonography (CUS) have
      been widely validated [2, 3].

      Clinical probability assessment by clinical prediction rules (CPRs) is a crucial step in the
      management of suspected DVT. However, the most commonly used CPR for DVT, the Wells' score,
      has never been validated in pregnant women [3]. Recently, the 'LEFt' clinical prediction rule
      was derived and internally validated by Chan et al. among 194 pregnant women investigated for
      suspected DVT[4]. This rule combines three variables: symptoms in the left leg ("L"), calf
      circumference difference equal or greater than 2 centimeters ("E" for edema) and first
      trimester presentation ("Ft") [4].

      We performed an external validation of this rule on a recently published prospective cohort
      of pregnant patients with suspected DVT (submitted to JTH). This external validation showed
      that a negative "LEFt" rule accurately identified pregnant women in whom the proportion of
      confirmed DVT appears to be very low. A prospective validation of this rule is now warranted,
      and we plan to use it in our prospective study.

      The second step used in the diagnostic strategy including non-pregnant patients is D-dimer
      measurement. The test has been widely validated in non-pregnant patients and, in association
      with a non-high clinical probability, it allows to safely rule out DVT [5].

      As D-dimer level raise steadily during pregnancy, the specificity of the test decreases and
      it is less useful in pregnant women. A recent study suggested that the currently available
      sensitive D-dimer assays that are used for the exclusion in symptomatic non-pregnant women
      have the potential to exclude DVT in symptomatic pregnant women with the application of
      higher cut-points [6]. Even if this data arises from a small study, it clearly suggests that
      the usual cut-off set a 500 ng/ml would safely rule out DVT in pregnant women [6]. As the
      usual cut-off has never been prospectively validated in pregnant women with suspected DVT, we
      would like, as a first step, to use it in our study.

      In pregnant patients, limited data is available on the use of complete compression
      ultrasonography to rule out DVT. In a recent prospective management study, we included 226
      pregnant and post-partum women with suspected lower limb DVT. We observed a 1.1% (95%
      CI:0.3-4.0) three-month thromboembolic event rate in those left untreated on the basis of a
      negative single complete CUS [7]. This result is in line with what was reported after a
      normal phlebography, the gold standard test [8].

      Even if complete CUS is safe to rule out DVT in pregnant women, current diagnostic strategies
      for suspected DVT in non-pregnant patients rely on the use of clinical probability and
      D-Dimer prior to leg veins imaging [5]. However, no management outcome study on the safety
      and usefulness of D-Dimer to rule out DVT in pregnant women is available to date. Another
      limitation of the strategies based on a single unique complete CUS, is that every woman has
      to undergo complete CUS. However, this test is not always available. Therefore, a strategy in
      which the association of clinical probability assessment and D-dimer measurement would allow
      to safely rule out DVT in a significant proportion of patients without performing a complete
      CUS, would be of great help in everyday clinical practice and would probably be
      cost-effective.

      Therefore, we plan a prospective study to assess the safety of a sequential diagnostic
      strategy based on the assessment of clinical probability with the LEFt rule, D-dimer
      measurement and complete CUS in pregnant women with suspected DVT.
observational model: Cohort
time perspective: Prospective
measure: The main outcome will be the number of thromboembolic recurrent events (DVT, PE, death attributable to venous thromboembolic disease) documented during the three-month follow-up in the patients left untreated on the basis of a normal diagnostic strategy.
time frame: 3 years
description: Rate of thromboembolic events after a normal diagnostic strategy.
measure: Prospective evaluation of the diagnostic performances of the LEFt rule.
time frame: 3 years
description: Prospective validation of the LEFt rule.
measure: Prospective evaluation of D-dimer measurement to rule out DVT in pregnant women.
time frame: 3 years
description: Prospective evaluation of the diagnostic performances of D-dimer measurement in pregnant women with suspected DVT.
arm group label: Pregnant women
description: Pregnant women with suspected DVT assessed by the LEFt rule, D-dimer measurement and complete ultrasonography.
intervention type: Other
intervention name: Left rule, D-dimer measurement and complete ultrasonography in pregnant women.
description: Diagnostic strategy based on the LEFt rule, D-dimer measurement and complete ultrasonography
arm group label: Pregnant women
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Grégoire Le Gal, MD
role: Principal Investigator
affiliation: The Ottawa Hospital
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Switzerland
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Marc Righini
investigator title: Principal investigator
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Fibrin fragment D