<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/NCT03018431</url>
  </required_header>
  <id_info>
    <org_study_id>CHBesançon</org_study_id>
    <nct_id>NCT03018431</nct_id>
  </id_info>
  <brief_title>CT Scan and Lung Ultrasonography to Improve Diagnostic of Ventilation Acquired Pneumonia in ICU</brief_title>
  <acronym>ECTOPICUS</acronym>
  <official_title>Impact of CT Scan and Lung Ultrasonogrpahy in Early Diagnostic Accuracy for Ventilation Acquired Lower Respiratory Tract Infections in Intensive Care Units.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Besancon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Besancon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We aim to show that systematic ultrasonography performed in ventilated patients suspected of&#xD;
      ventilation-acquired pneumonia could improve the accuracy of diagnostic of pneumonia, and&#xD;
      helps defining the diagnostic of tracheobronchitis when lower respiratory tract infection is&#xD;
      considered.&#xD;
&#xD;
      Chest CT scan is often performed before or just after admission in ICU, and usually show&#xD;
      abnormalities that are revealed later on standard radiographs.&#xD;
&#xD;
      This last exam is traditionally considered as the gold standard to prove new pulmonary&#xD;
      infiltrates, but the correlation with parenchymal consolidation is pretty low, and lead to&#xD;
      over-diagnosing pneumonia, thus leading to a massive and maybe sometimes unconsidered&#xD;
      prescription of antibiotic therapy.&#xD;
&#xD;
      Lung ultrasonography conducted systematically within the 3 first days after suspcion of&#xD;
      pneumonia could help making the difference between real infection-linked lesions, and banal&#xD;
      abnormalities following the hydric inflation of intra-thoracic organs, for instance pulmonary&#xD;
      edema or pleural effusion.&#xD;
&#xD;
      An independent evaluation using lung ultrasound, and analysis of CT scan acquisition when&#xD;
      performed, compared with the physician in charge of the patient appreciation by suggesting&#xD;
      him to provide his own probability of pneumonia upon routine clinical and biological datas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diagnostic of VAP and tracheobronchitis is often difficult in UC under mechanical&#xD;
      ventilation, and usually occuring quite early after initial phase of hemodynamic instability,&#xD;
      and characterized by needs of massive fluids supports and drugs infusion. The goldstandard is&#xD;
      still standard chest X-ray, providing a picture of the whole abnormalities due to cardiac&#xD;
      failure, and cardiogenic pulmonary edema. The high rate of water in chest of the patients&#xD;
      under ventilation assistance and hemodynamic support is responsible of a misinterpretation of&#xD;
      the abnormalities visualized on the radiographs. It is often considered that Lung&#xD;
      ultrasonography is useful to appreciate the involvement of pleural effusion, explaning&#xD;
      etiologies of hypoxemia, where cardiac failure is excluded by the simultaneous&#xD;
      ultrasonographic evaluation. However, it is not well recognized that pulmonary parenchyma can&#xD;
      be explored through echography, and that it provides a lot of information about the amount of&#xD;
      liquid inside it, and the default of aeration. Thus, it can in real time help the physician&#xD;
      to guide the therapeutics and manage the ventilation better. Moreover, the suspicion of&#xD;
      infection, clinically and biologically leads to the early prescription of antibiotics, given&#xD;
      that the radiography is abnormal. Knowing that there is now parenchymal consolidation but&#xD;
      rather effusion or a certain degree of pulmonary edema could help avoiding treating falsely a&#xD;
      respiratory infection.&#xD;
&#xD;
      The same thoughts can be held concerning Chest CT Scan, an exam often realized at the early&#xD;
      stage of management in a critical situation. We can take for granted that when occurring in&#xD;
      the 48 first hours of resuscitation, this exam shows in a certain number of cases preexisting&#xD;
      abnormalities, that are revealed severla hours later by Chest radiograph, when the suspicion&#xD;
      of respiratory infection acquired under ventilation emerge. If we take into account that&#xD;
      these abnormalities seen on radiographs are just correlated to those that could be seen on&#xD;
      CT, but with a certain delay, and are not de novo, it could lead to an overestimating of&#xD;
      ventilation acquired pneumonia, because the criteria of a new radiographic infiltrate won't&#xD;
      be valid anymore. The diagnostic of tracheobronchitis could then be more appropriated in a&#xD;
      certain number of situations.&#xD;
&#xD;
      Our aim is to verify retrospectively by an adjudication committee, that this early CT Scan,&#xD;
      within the 2 first days after admission if patient is ventilated and/or suspicion of lower&#xD;
      respiratory tract infection, and a systematic lung ultrasonographic evaluation, provided by&#xD;
      an independent operator, could change our appreciation of the frequency of&#xD;
      ventilation-acquired pneumonia, comparing to the appreciation of th physician in charge of&#xD;
      the patients.&#xD;
&#xD;
      We are thus conducting a repeated evaluation, at day 0, day 3 and day 7 with ultrasonography,&#xD;
      in order to give a probability of pneumonia or tracheobronchitis by the echographist&#xD;
      operator, and suggesting the physician to give his own probability based on clinical and&#xD;
      biological routine datas. We then measure the rate of agreement between the two parts, to see&#xD;
      how far the systematic evaluation using pleural ultrasonography could help defining the&#xD;
      probability of infection, and validating the diagnostic of pneumonia. The impact should be to&#xD;
      improve the accuracy within the first days 2 or 3 days after suspicion, when repeated, if&#xD;
      possible by the same operator. One of the main benefit could be the reduction or better&#xD;
      reevaluation of antibiotic therapy, if diagnostic of pneumonia is rejected secondary,&#xD;
      eventually shorter course of treatment could be chosen, even if this point deserve to be&#xD;
      evaluated in further studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 15, 2017</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>18 Days</target_duration>
  <primary_outcome>
    <measure>Concordance of diagnostic of tracheo-bronchitis or pneumonia under mechanical ventilation, between physician in charge and independent observator cunducting ultrasound and CT scan evaluation.</measure>
    <time_frame>8 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>rate of agreement between radiographs, CT scan and lung ultrasonography</measure>
    <time_frame>8 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>correlation between evolution according to management of infection and misdiagnostic of pneumonia or tracheo-bronchitis or not by the clinician.</measure>
    <time_frame>8 days</time_frame>
    <description>improving under treatment or worsening without antibiotic therapy when pneumonia diagnostic is valid or not, making further considering the management of antibiotic therapy by the physician guided by CT scan and/or ultrasonography.&#xD;
quantifying amount of situations when diagnostic of pneumonia is validated retrospectively by the adjudication, and delayed starting of antibiotics when diagnostic is not patent early in the standard evaluation, thus conducting to an increased risk of morbi-mortality.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Ventilator-Associated Pneumonia</condition>
  <condition>Tracheobronchitis</condition>
  <arm_group>
    <arm_group_label>Physician routine evaluation</arm_group_label>
    <description>systematic evaluation of the probability of tracheobronchitis or pneumonia based upon clinical and biological, associated with standard radiographs, performed by the physician in chrage of the patient.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>independent evaluation</arm_group_label>
    <description>systematic evaluation of the probability of tracheobronchitis or pneumonia based upon early CT scan, and repeated lung ultrasonography, performed by an independent operator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CT Scan</intervention_name>
    <description>patients undergoing chest CT scan at admission and repeated lung ultrasonography</description>
    <arm_group_label>independent evaluation</arm_group_label>
    <other_name>Ultrasonography</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Every patient place under mechanical ventilation at least for 48 hours, suspected of lower&#xD;
        respiratory tract infection, based on CDC criterias of ventilatior-acquired pneumonia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Immunocompetent subject,&#xD;
&#xD;
          -  fever and/or purulent tracheal secretions and/or hyperleukocytosis or leukopenia,&#xD;
             associated with a positive microbiological sample (within broncho-alveolar leakage,&#xD;
             endotracheal aspiration, or distal sample),&#xD;
&#xD;
          -  invasive mechanical ventilation initiated since at least 48hours, and suppose to be&#xD;
             maintained for at least 48hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Immunocompromised-patients defined by ; HIV treated or not, patient under&#xD;
             corticotherapy, immunotherapy, inflammatory systemic diseases, solid organ transplant,&#xD;
             solid tumor treated or not, bone marrow transplant or stem cells graft, hematological&#xD;
             malignancy known or under treatment,&#xD;
&#xD;
          -  moribond,&#xD;
&#xD;
          -  ventilation expected to last less than 48hours,&#xD;
&#xD;
          -  minor-aged patients,&#xD;
&#xD;
          -  no social insurance or isolation,&#xD;
&#xD;
          -  mental disability making the understanding of the purpose of too difficult.&#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>Lila Bouadma, MD,PhD</last_name>
    <role>Study Director</role>
    <affiliation>Hôpital universitaire Bichat- Claude Bernard</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Paul-Henri WICKY, MD</last_name>
    <phone>003680129209</phone>
    <email>phwicky@outlook.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Universitaire Jean Minjoz</name>
      <address>
        <city>Besancon</city>
        <state>Doubs</state>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Paul-Henri WICKY</last_name>
      <phone>003680129209</phone>
      <email>phwicky@outook.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital Bichat - Claude Bernard</name>
      <address>
        <city>Paris</city>
        <zip>75 018</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Haddam M, Zieleskiewicz L, Perbet S, Baldovini A, Guervilly C, Arbelot C, Noel A, Vigne C, Hammad E, Antonini F, Lehingue S, Peytel E, Lu Q, Bouhemad B, Golmard JL, Langeron O, Martin C, Muller L, Rouby JJ, Constantin JM, Papazian L, Leone M; CAR'Echo Collaborative Network; AzuRea Collaborative Network. Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS. Intensive Care Med. 2016 Oct;42(10):1546-1556. doi: 10.1007/s00134-016-4411-7. Epub 2016 Jun 20.</citation>
    <PMID>27324241</PMID>
  </results_reference>
  <results_reference>
    <citation>Mongodi S, Via G, Girard M, Rouquette I, Misset B, Braschi A, Mojoli F, Bouhemad B. Lung Ultrasound for Early Diagnosis of Ventilator-Associated Pneumonia. Chest. 2016 Apr;149(4):969-80. doi: 10.1016/j.chest.2015.12.012. Epub 2015 Dec 22.</citation>
    <PMID>26836896</PMID>
  </results_reference>
  <results_reference>
    <citation>Martin-Loeches I, Povoa P, Rodriguez A, Curcio D, Suarez D, Mira JP, Cordero ML, Lepecq R, Girault C, Candeias C, Seguin P, Paulino C, Messika J, Castro AG, Valles J, Coelho L, Rabello L, Lisboa T, Collins D, Torres A, Salluh J, Nseir S; TAVeM study. Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med. 2015 Nov;3(11):859-68. doi: 10.1016/S2213-2600(15)00326-4. Epub 2015 Oct 22.</citation>
    <PMID>26472037</PMID>
  </results_reference>
  <results_reference>
    <citation>Claessens YE, Debray MP, Tubach F, Brun AL, Rammaert B, Hausfater P, Naccache JM, Ray P, Choquet C, Carette MF, Mayaud C, Leport C, Duval X. Early Chest Computed Tomography Scan to Assist Diagnosis and Guide Treatment Decision for Suspected Community-acquired Pneumonia. Am J Respir Crit Care Med. 2015 Oct 15;192(8):974-82. doi: 10.1164/rccm.201501-0017OC.</citation>
    <PMID>26168322</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>September 10, 2017</last_update_submitted>
  <last_update_submitted_qc>September 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre Hospitalier Universitaire de Besancon</investigator_affiliation>
    <investigator_full_name>Paul-Henri WICKY</investigator_full_name>
    <investigator_title>Medicla Doctor</investigator_title>
  </responsible_party>
  <keyword>Lung ultrasonography</keyword>
  <keyword>Chest CT scan</keyword>
  <keyword>ventilator-associated pneumonia</keyword>
  <keyword>ventilator-associated tracheobronchitis</keyword>
  <keyword>antibiotic stewardship</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Ventilator-Associated</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/NCT03018431
org study id: CHBesançon
nct id: NCT03018431
lead sponsor: 
has dmc: No
We aim to show that systematic ultrasonography performed in ventilated patients suspected of
      ventilation-acquired pneumonia could improve the accuracy of diagnostic of pneumonia, and
      helps defining the diagnostic of tracheobronchitis when lower respiratory tract infection is
      considered.

      Chest CT scan is often performed before or just after admission in ICU, and usually show
      abnormalities that are revealed later on standard radiographs.

      This last exam is traditionally considered as the gold standard to prove new pulmonary
      infiltrates, but the correlation with parenchymal consolidation is pretty low, and lead to
      over-diagnosing pneumonia, thus leading to a massive and maybe sometimes unconsidered
      prescription of antibiotic therapy.

      Lung ultrasonography conducted systematically within the 3 first days after suspcion of
      pneumonia could help making the difference between real infection-linked lesions, and banal
      abnormalities following the hydric inflation of intra-thoracic organs, for instance pulmonary
      edema or pleural effusion.

      An independent evaluation using lung ultrasound, and analysis of CT scan acquisition when
      performed, compared with the physician in charge of the patient appreciation by suggesting
      him to provide his own probability of pneumonia upon routine clinical and biological datas.
Diagnostic of VAP and tracheobronchitis is often difficult in UC under mechanical
      ventilation, and usually occuring quite early after initial phase of hemodynamic instability,
      and characterized by needs of massive fluids supports and drugs infusion. The goldstandard is
      still standard chest X-ray, providing a picture of the whole abnormalities due to cardiac
      failure, and cardiogenic pulmonary edema. The high rate of water in chest of the patients
      under ventilation assistance and hemodynamic support is responsible of a misinterpretation of
      the abnormalities visualized on the radiographs. It is often considered that Lung
      ultrasonography is useful to appreciate the involvement of pleural effusion, explaning
      etiologies of hypoxemia, where cardiac failure is excluded by the simultaneous
      ultrasonographic evaluation. However, it is not well recognized that pulmonary parenchyma can
      be explored through echography, and that it provides a lot of information about the amount of
      liquid inside it, and the default of aeration. Thus, it can in real time help the physician
      to guide the therapeutics and manage the ventilation better. Moreover, the suspicion of
      infection, clinically and biologically leads to the early prescription of antibiotics, given
      that the radiography is abnormal. Knowing that there is now parenchymal consolidation but
      rather effusion or a certain degree of pulmonary edema could help avoiding treating falsely a
      respiratory infection.

      The same thoughts can be held concerning Chest CT Scan, an exam often realized at the early
      stage of management in a critical situation. We can take for granted that when occurring in
      the 48 first hours of resuscitation, this exam shows in a certain number of cases preexisting
      abnormalities, that are revealed severla hours later by Chest radiograph, when the suspicion
      of respiratory infection acquired under ventilation emerge. If we take into account that
      these abnormalities seen on radiographs are just correlated to those that could be seen on
      CT, but with a certain delay, and are not de novo, it could lead to an overestimating of
      ventilation acquired pneumonia, because the criteria of a new radiographic infiltrate won't
      be valid anymore. The diagnostic of tracheobronchitis could then be more appropriated in a
      certain number of situations.

      Our aim is to verify retrospectively by an adjudication committee, that this early CT Scan,
      within the 2 first days after admission if patient is ventilated and/or suspicion of lower
      respiratory tract infection, and a systematic lung ultrasonographic evaluation, provided by
      an independent operator, could change our appreciation of the frequency of
      ventilation-acquired pneumonia, comparing to the appreciation of th physician in charge of
      the patients.

      We are thus conducting a repeated evaluation, at day 0, day 3 and day 7 with ultrasonography,
      in order to give a probability of pneumonia or tracheobronchitis by the echographist
      operator, and suggesting the physician to give his own probability based on clinical and
      biological routine datas. We then measure the rate of agreement between the two parts, to see
      how far the systematic evaluation using pleural ultrasonography could help defining the
      probability of infection, and validating the diagnostic of pneumonia. The impact should be to
      improve the accuracy within the first days 2 or 3 days after suspicion, when repeated, if
      possible by the same operator. One of the main benefit could be the reduction or better
      reevaluation of antibiotic therapy, if diagnostic of pneumonia is rejected secondary,
      eventually shorter course of treatment could be chosen, even if this point deserve to be
      evaluated in further studies.
observational model: Cohort
time perspective: Prospective
measure: Concordance of diagnostic of tracheo-bronchitis or pneumonia under mechanical ventilation, between physician in charge and independent observator cunducting ultrasound and CT scan evaluation.
time frame: 8 days
measure: rate of agreement between radiographs, CT scan and lung ultrasonography
time frame: 8 days
measure: correlation between evolution according to management of infection and misdiagnostic of pneumonia or tracheo-bronchitis or not by the clinician.
time frame: 8 days
description: improving under treatment or worsening without antibiotic therapy when pneumonia diagnostic is valid or not, making further considering the management of antibiotic therapy by the physician guided by CT scan and/or ultrasonography.
quantifying amount of situations when diagnostic of pneumonia is validated retrospectively by the adjudication, and delayed starting of antibiotics when diagnostic is not patent early in the standard evaluation, thus conducting to an increased risk of morbi-mortality.
arm group label: Physician routine evaluation
description: systematic evaluation of the probability of tracheobronchitis or pneumonia based upon clinical and biological, associated with standard radiographs, performed by the physician in chrage of the patient.
arm group label: independent evaluation
description: systematic evaluation of the probability of tracheobronchitis or pneumonia based upon early CT scan, and repeated lung ultrasonography, performed by an independent operator.
intervention type: Other
intervention name: CT Scan
description: patients undergoing chest CT scan at admission and repeated lung ultrasonography
arm group label: independent evaluation
other name: Ultrasonography
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lila Bouadma, MD,PhD
role: Study Director
affiliation: Hôpital universitaire Bichat- Claude Bernard
last name: Paul-Henri WICKY, MD
phone: 003680129209
email: phwicky@outlook.fr
facility: 
contact: 
facility: 
country: France
citation: Haddam M, Zieleskiewicz L, Perbet S, Baldovini A, Guervilly C, Arbelot C, Noel A, Vigne C, Hammad E, Antonini F, Lehingue S, Peytel E, Lu Q, Bouhemad B, Golmard JL, Langeron O, Martin C, Muller L, Rouby JJ, Constantin JM, Papazian L, Leone M; CAR'Echo Collaborative Network; AzuRea Collaborative Network. Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS. Intensive Care Med. 2016 Oct;42(10):1546-1556. doi: 10.1007/s00134-016-4411-7. Epub 2016 Jun 20.
PMID: 27324241
citation: Mongodi S, Via G, Girard M, Rouquette I, Misset B, Braschi A, Mojoli F, Bouhemad B. Lung Ultrasound for Early Diagnosis of Ventilator-Associated Pneumonia. Chest. 2016 Apr;149(4):969-80. doi: 10.1016/j.chest.2015.12.012. Epub 2015 Dec 22.
PMID: 26836896
citation: Martin-Loeches I, Povoa P, Rodriguez A, Curcio D, Suarez D, Mira JP, Cordero ML, Lepecq R, Girault C, Candeias C, Seguin P, Paulino C, Messika J, Castro AG, Valles J, Coelho L, Rabello L, Lisboa T, Collins D, Torres A, Salluh J, Nseir S; TAVeM study. Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med. 2015 Nov;3(11):859-68. doi: 10.1016/S2213-2600(15)00326-4. Epub 2015 Oct 22.
PMID: 26472037
citation: Claessens YE, Debray MP, Tubach F, Brun AL, Rammaert B, Hausfater P, Naccache JM, Ray P, Choquet C, Carette MF, Mayaud C, Leport C, Duval X. Early Chest Computed Tomography Scan to Assist Diagnosis and Guide Treatment Decision for Suspected Community-acquired Pneumonia. Am J Respir Crit Care Med. 2015 Oct 15;192(8):974-82. doi: 10.1164/rccm.201501-0017OC.
PMID: 26168322
responsible party type: Principal Investigator
investigator affiliation: Centre Hospitalier Universitaire de Besancon
investigator full name: Paul-Henri WICKY
investigator title: Medicla Doctor
mesh term: Pneumonia
mesh term: Pneumonia, Ventilator-Associated
sharing ipd: No