<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/NCT03270215</url>
  </required_header>
  <id_info>
    <org_study_id>CT-UPE</org_study_id>
    <nct_id>NCT03270215</nct_id>
  </id_info>
  <brief_title>The Added Value of CT Scanning in Patients With an Unilateral Pleural Effusion</brief_title>
  <official_title>The Added Value of CT Scanning for Discriminating Malignant From Non-malignant Causes in Patients With an Unilateral Pleural Effusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Naestved Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Naestved 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>
      To investigate the diagnostic power of computed tomography for discriminating malignant from&#xD;
      nonmalignant causes to pleural effusions in consecutive patients with no malignant cells&#xD;
      found at a cytological examination and a chest x-ray not suspicious of malignancy. The&#xD;
      investigators hypothesised that the combination improves the chance of detecting the cause of&#xD;
      the pleural effusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives&#xD;
&#xD;
        1. Is CT-scanning better than chest x-ray plus a thoracocentesis for discriminating&#xD;
           malignant from benign pleural effusions?&#xD;
&#xD;
        2. What is the added value of a CT-scanning to chest x-ray plus thoracocentesis for&#xD;
           discriminating malignant from benign pleural effusions?&#xD;
&#xD;
      The above measured as, true positive, true negative, false positive, false negative,&#xD;
      sensitivity, specificity, likelihood ratio+, likelihood ratio -, positive predictive value,&#xD;
      negative predictive value and diagnostic accuracy.&#xD;
&#xD;
      Study design A retrospective diagnostic study including consecutive patients with a&#xD;
      unilateral pleural effusion. Thoracocentesis, chest x-ray and CT findings are categorised as&#xD;
      either normal (i.e. not suggestive of any aetiology of the unilateral pleural effusion),&#xD;
      suggestive of other lung pathology or suggestive of malignancy (i.e. representing a possible&#xD;
      aetiology of the unilateral pleural effusion). The final diagnosis is extracted from the&#xD;
      patients' electronic medical records. When no diagnosis is found, two investigators agree on&#xD;
      a consensus diagnosis based on all investigation results. If no reasonable diagnosis can be&#xD;
      established based on the findings, the patient case is categorised as having no final&#xD;
      diagnosis.&#xD;
&#xD;
      The investigators follow the STARD guideline for reporting diagnostic accuracy studies.&#xD;
&#xD;
      Patients The investigators will include consecutive patients presenting with a unilateral&#xD;
      pleural effusion between 01 January 2013 and 31 December 2016. The patients will be&#xD;
      identified searching the hospitals administrative patient system for the procedure code&#xD;
      thoracocentesis (KTGA30).&#xD;
&#xD;
      Departments of Respiratory Medicine at Zealand University Hospital, Roskilde and Naestved&#xD;
      Hospital, Region Zealand, Denmark, participate in this study. Both hospitals are a large&#xD;
      tertiary hospital with specialised functions. Patients older than 16 years are included,&#xD;
      irrespective of smoking history and comorbidities, if both thoracocentesis, chest x-ray and a&#xD;
      CT-scanning are performed. Exclusion criteria are previously diagnosed lung cancer, thoracic&#xD;
      malignancy or incomplete data.&#xD;
&#xD;
      Data Relevant data on demographics, descriptive data, symptoms, medical history and&#xD;
      diagnostic workup will be extracted from electronic medical records, and registered in the&#xD;
      individual patient's case report file (CRF). The CRF is stored using Excel on an encrypted&#xD;
      USB-key, the USB-key will be stored behind double lock (room plus cupboard).&#xD;
      Background-variables will be utilised to describe the study population and for explorative&#xD;
      research. Only study coordinators will have access to data. Computers, as well as a back-up,&#xD;
      will be stored and kept in a locked cupboard in a locked room. Only study coordinators&#xD;
      possess relevant keys.&#xD;
&#xD;
      Statistics Data will be presented as frequencies and/or mean ± standard deviation (SD). Test&#xD;
      characteristics will be compared using McNemar's test with a Bonferroni correction. An alpha&#xD;
      level of 0.05 is considered significant. Test characteristics for thoracocentesis, chest&#xD;
      x-ray and CT-scanning and the combination of the three will be calculated. Test&#xD;
      characteristics are true positive, true negative, false positive, false negative,&#xD;
      sensitivity, specificity, likelihood ratio+, likelihood ratio-, positive predictive value,&#xD;
      negative predictive value and diagnostic accuracy.&#xD;
&#xD;
      The combined sensitivity of two parallel tests will be calculated using the formula:&#xD;
&#xD;
      The sensitivity of test A + sensitivity of test B - (sensitivity of test A x sensitivity of&#xD;
      test B)&#xD;
&#xD;
      The combined specificity for two parallel tests will be calculated using the formula:&#xD;
&#xD;
      The specificity of test A x specificity of test B&#xD;
&#xD;
      The combined sensitivity of three parallel tests will be calculated using the formula:&#xD;
&#xD;
      The sensitivity of test A + sensitivity of test B + sensitivity of test C - (sensitivity of&#xD;
      test A x sensitivity of test B x sensitivity of test C)&#xD;
&#xD;
      The combined specificity for three parallel tests will be calculated using the formula:&#xD;
&#xD;
      The specificity of test A x specificity of test B x sensitivity of test C For data analysis,&#xD;
      we use STATA (StataCorp LLC, Version 15.0, College Station, Texas, USA).&#xD;
&#xD;
      Ethics The study is retrospective and observational and thus will not affect the included&#xD;
      patients. Before any study-related activity, the protocol and study must be approved by the&#xD;
      Danish Data Protection Agency and the local Committee on Biomedical Research Ethics. All&#xD;
      results will be stored and analysed by computer, and the investigators secure the patients'&#xD;
      anonymity according to the national laws. The data are anonymized and stored after completion&#xD;
      of the study and data containing personal identification numbers will be kept behind&#xD;
      double-lock at the department.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">January 30, 2019</completion_date>
  <primary_completion_date type="Actual">January 31, 2018</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Specificity</measure>
    <time_frame>1 year</time_frame>
    <description>TN / (TN+FP)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic accuracy</measure>
    <time_frame>1 year</time_frame>
    <description>(TP+TN) / (TP+TN+FP+FN)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Likelihood ratio +</measure>
    <time_frame>1 year</time_frame>
    <description>LR+ = sensitivity / (1-specificity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Likelihood ratio -</measure>
    <time_frame>1 year</time_frame>
    <description>LR- = (1-sensitivity) / specificity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive predictive value</measure>
    <time_frame>1 year</time_frame>
    <description>PPV =TP / (TP+ FP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Negative predictive value</measure>
    <time_frame>1 year</time_frame>
    <description>TN/ (TN + FN)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity</measure>
    <time_frame>1 year</time_frame>
    <description>TP / (TP + FN)</description>
  </secondary_outcome>
  <enrollment type="Actual">232</enrollment>
  <condition>Pleural Effusion, Malignant</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Computed tomography</intervention_name>
    <description>The diagnostic power to discriminate malignant from nonmalignant causes of e pleural effusion</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All patients with a unilateral pleural effusion of unknown origin&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Thoracocentesis&#xD;
&#xD;
          -  Chest X-ray and&#xD;
&#xD;
          -  CT-scanning are performed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lung cancer&#xD;
&#xD;
          -  Other thoracic malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Naestved Hospital</name>
      <address>
        <city>Naestved</city>
        <zip>4700</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Naestved Hospital</name>
      <address>
        <city>Næstved</city>
        <zip>4700</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>December 15, 2020</last_update_submitted>
  <last_update_submitted_qc>December 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Naestved Hospital</investigator_affiliation>
    <investigator_full_name>Simon Reuter</investigator_full_name>
    <investigator_title>Ph.d.student</investigator_title>
  </responsible_party>
  <keyword>Computed Tomography</keyword>
  <keyword>Specificity</keyword>
  <keyword>Sensitivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pleural Effusion, Malignant</mesh_term>
    <mesh_term>Pleural Effusion</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/NCT03270215
org study id: CT-UPE
nct id: NCT03270215
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To investigate the diagnostic power of computed tomography for discriminating malignant from
      nonmalignant causes to pleural effusions in consecutive patients with no malignant cells
      found at a cytological examination and a chest x-ray not suspicious of malignancy. The
      investigators hypothesised that the combination improves the chance of detecting the cause of
      the pleural effusion.
Objectives

        1. Is CT-scanning better than chest x-ray plus a thoracocentesis for discriminating
           malignant from benign pleural effusions?

        2. What is the added value of a CT-scanning to chest x-ray plus thoracocentesis for
           discriminating malignant from benign pleural effusions?

      The above measured as, true positive, true negative, false positive, false negative,
      sensitivity, specificity, likelihood ratio+, likelihood ratio -, positive predictive value,
      negative predictive value and diagnostic accuracy.

      Study design A retrospective diagnostic study including consecutive patients with a
      unilateral pleural effusion. Thoracocentesis, chest x-ray and CT findings are categorised as
      either normal (i.e. not suggestive of any aetiology of the unilateral pleural effusion),
      suggestive of other lung pathology or suggestive of malignancy (i.e. representing a possible
      aetiology of the unilateral pleural effusion). The final diagnosis is extracted from the
      patients' electronic medical records. When no diagnosis is found, two investigators agree on
      a consensus diagnosis based on all investigation results. If no reasonable diagnosis can be
      established based on the findings, the patient case is categorised as having no final
      diagnosis.

      The investigators follow the STARD guideline for reporting diagnostic accuracy studies.

      Patients The investigators will include consecutive patients presenting with a unilateral
      pleural effusion between 01 January 2013 and 31 December 2016. The patients will be
      identified searching the hospitals administrative patient system for the procedure code
      thoracocentesis (KTGA30).

      Departments of Respiratory Medicine at Zealand University Hospital, Roskilde and Naestved
      Hospital, Region Zealand, Denmark, participate in this study. Both hospitals are a large
      tertiary hospital with specialised functions. Patients older than 16 years are included,
      irrespective of smoking history and comorbidities, if both thoracocentesis, chest x-ray and a
      CT-scanning are performed. Exclusion criteria are previously diagnosed lung cancer, thoracic
      malignancy or incomplete data.

      Data Relevant data on demographics, descriptive data, symptoms, medical history and
      diagnostic workup will be extracted from electronic medical records, and registered in the
      individual patient's case report file (CRF). The CRF is stored using Excel on an encrypted
      USB-key, the USB-key will be stored behind double lock (room plus cupboard).
      Background-variables will be utilised to describe the study population and for explorative
      research. Only study coordinators will have access to data. Computers, as well as a back-up,
      will be stored and kept in a locked cupboard in a locked room. Only study coordinators
      possess relevant keys.

      Statistics Data will be presented as frequencies and/or mean ± standard deviation (SD). Test
      characteristics will be compared using McNemar's test with a Bonferroni correction. An alpha
      level of 0.05 is considered significant. Test characteristics for thoracocentesis, chest
      x-ray and CT-scanning and the combination of the three will be calculated. Test
      characteristics are true positive, true negative, false positive, false negative,
      sensitivity, specificity, likelihood ratio+, likelihood ratio-, positive predictive value,
      negative predictive value and diagnostic accuracy.

      The combined sensitivity of two parallel tests will be calculated using the formula:

      The sensitivity of test A + sensitivity of test B - (sensitivity of test A x sensitivity of
      test B)

      The combined specificity for two parallel tests will be calculated using the formula:

      The specificity of test A x specificity of test B

      The combined sensitivity of three parallel tests will be calculated using the formula:

      The sensitivity of test A + sensitivity of test B + sensitivity of test C - (sensitivity of
      test A x sensitivity of test B x sensitivity of test C)

      The combined specificity for three parallel tests will be calculated using the formula:

      The specificity of test A x specificity of test B x sensitivity of test C For data analysis,
      we use STATA (StataCorp LLC, Version 15.0, College Station, Texas, USA).

      Ethics The study is retrospective and observational and thus will not affect the included
      patients. Before any study-related activity, the protocol and study must be approved by the
      Danish Data Protection Agency and the local Committee on Biomedical Research Ethics. All
      results will be stored and analysed by computer, and the investigators secure the patients'
      anonymity according to the national laws. The data are anonymized and stored after completion
      of the study and data containing personal identification numbers will be kept behind
      double-lock at the department.
observational model: Cohort
time perspective: Retrospective
measure: Specificity
time frame: 1 year
description: TN / (TN+FP)
measure: Diagnostic accuracy
time frame: 1 year
description: (TP+TN) / (TP+TN+FP+FN)
measure: Likelihood ratio +
time frame: 1 year
description: LR+ = sensitivity / (1-specificity)
measure: Likelihood ratio -
time frame: 1 year
description: LR- = (1-sensitivity) / specificity
measure: Positive predictive value
time frame: 1 year
description: PPV =TP / (TP+ FP)
measure: Negative predictive value
time frame: 1 year
description: TN/ (TN + FN)
measure: Sensitivity
time frame: 1 year
description: TP / (TP + FN)
intervention type: Procedure
intervention name: Computed tomography
description: The diagnostic power to discriminate malignant from nonmalignant causes of e pleural effusion
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Naestved Hospital
investigator full name: Simon Reuter
investigator title: Ph.d.student
mesh term: Pleural Effusion, Malignant
mesh term: Pleural Effusion