<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/NCT01695499</url>
  </required_header>
  <id_info>
    <org_study_id>BAL-Biomarker-ICU Study</org_study_id>
    <secondary_id>Grant Pfizer ASPIRE Award</secondary_id>
    <nct_id>NCT01695499</nct_id>
  </id_info>
  <brief_title>Diagnostic Study of Biomarkers in BAL of ICU Patients With Lung Infiltrates</brief_title>
  <official_title>Open, Prospective, Multicenter Trial to Evaluate the Clinical Significance of Combined Serological (Galactomannan ELISA, Beta D Glucan Assay) and Molecular (Nested Aspergillus PCR Assay, Real-time qPCR Assay, Multifungal DNA Microarray) Diagnostic Assays to Detect and Characterize Fungal Pathogens in Bronchoalveolar Lavage (BAL)and Blood Samples of Intensive Care Unit Patients With Pulmonary Infiltrates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heidelberg University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Heidelberg University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this project is therefore to explore on the clinical significance of analyzing&#xD;
      surrogate markers combined with conventional diagnostics in the ICU setting. BAL, blood and&#xD;
      biopsy samples will be subjected to a combined analysis of GM, BDG, Aspergillus specific PCR&#xD;
      assays in addition to conventional diagnostics (Microscopy, Culture,Histology) for ICU pts&#xD;
      with pulmonary infiltrates.&#xD;
&#xD;
      As GM and BDG are not species-specific, three established and repeatedly published species&#xD;
      specific PCR-based assays (nested PCR, real time PCR assay, multifungal DNA Array)developed&#xD;
      by our group will be investigated in combination with the serological tests in a multicenter&#xD;
      prospective clinical diagnostic trial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnostic accuracy of combined biomarker testing in BAL fluid in relation to diagnostic certainty</measure>
    <time_frame>6 weeks</time_frame>
    <description>Evaluation of diagnostic accuracy of the combined biomarker approach</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>INvasive Aspergillosis</condition>
  <condition>Mechanical Ventilation</condition>
  <condition>Lung Infiltrates</condition>
  <condition>Diagnostics</condition>
  <condition>Biomarker</condition>
  <arm_group>
    <arm_group_label>Immunosuppressed ICU Patients with lung infiltrates</arm_group_label>
    <description>Immunosuppressed ICU Patients with lung infiltrates</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>BAL and blood aliquots of 20 immunocompetent pts (suffering from lung diseases) will be collected and tested identically as a control population.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Only fungal DNA investigated&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Immunocompromised patients on the intensive care unit with lun infiltrates and one of the&#xD;
        following underlying conditions:&#xD;
&#xD;
          -  Underlying malignancy&#xD;
&#xD;
          -  Antineoplastic chemotherapy&#xD;
&#xD;
          -  Neutropenia&#xD;
&#xD;
          -  Allogeneic hematopoietic stem cell transplantation&#xD;
&#xD;
          -  Solid organ transplantation&#xD;
&#xD;
          -  Retransplantation&#xD;
&#xD;
          -  Acute or chronic immunological rejection or graft-versus-host-disease&#xD;
&#xD;
          -  Treatment with immunosuppressive agents (calcineurin inhibitors, OKT3, etc)&#xD;
&#xD;
          -  Profound systemic corticosteroid therapy prior to ICU admission&#xD;
&#xD;
          -  COPD Gold III/IV&#xD;
&#xD;
          -  Advanced liver cirrhosis and ICU treatment for more than 7 days&#xD;
&#xD;
          -  Hemodialysis, renal failure&#xD;
&#xD;
          -  CMV infection&#xD;
&#xD;
          -  HIV infection; CD4 cellcount&#xD;
&#xD;
          -  Post splenectomy&#xD;
&#xD;
          -  Post cardiac surgery&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  mechanical ventilation for more than 21 days&#xD;
&#xD;
          -  ICU-based steroid therapy and corticosteroid treatment for more than 7 days&#xD;
&#xD;
          -  Malnutrition&#xD;
&#xD;
          -  Severe burn wounds&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  underlying conditions (see above)&#xD;
&#xD;
          -  being on mechanical ventilation&#xD;
&#xD;
          -  lung infiltrates&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  immunocompetent patients (not fulfilling the criteria above)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mannheim University Hospital</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Reinwald M, Hummel M, Kovalevskaya E, Spiess B, Heinz WJ, Vehreschild JJ, Schultheis B, Krause SW, Claus B, Suedhoff T, Schwerdtfeger R, Reuter S, Kiehl MG, Hofmann WK, Buchheidt D. Therapy with antifungals decreases the diagnostic performance of PCR for diagnosing invasive aspergillosis in bronchoalveolar lavage samples of patients with haematological malignancies. J Antimicrob Chemother. 2012 Sep;67(9):2260-7. doi: 10.1093/jac/dks208. Epub 2012 Jun 27.</citation>
    <PMID>22740590</PMID>
  </reference>
  <reference>
    <citation>Reinwald M, Spiess B, Heinz WJ, Vehreschild JJ, Lass-Florl C, Kiehl M, Schultheis B, Krause SW, Wolf HH, Bertz H, Maschmeyer G, Hofmann WK, Buchheidt D. Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a multicenter prospective evaluation of an Aspergillus PCR assay and a galactomannan ELISA in bronchoalveolar lavage samples. Eur J Haematol. 2012 Aug;89(2):120-7. doi: 10.1111/j.1600-0609.2012.01806.x. Epub 2012 Jun 22.</citation>
    <PMID>22650156</PMID>
  </reference>
  <reference>
    <citation>Spiess B, Seifarth W, Merker N, Howard SJ, Reinwald M, Dietz A, Hofmann WK, Buchheidt D. Development of novel PCR assays to detect azole resistance-mediating mutations of the Aspergillus fumigatus cyp51A gene in primary clinical samples from neutropenic patients. Antimicrob Agents Chemother. 2012 Jul;56(7):3905-10. doi: 10.1128/AAC.05902-11. Epub 2012 Apr 23.</citation>
    <PMID>22526309</PMID>
  </reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <last_update_submitted>April 17, 2020</last_update_submitted>
  <last_update_submitted_qc>April 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Heidelberg University</investigator_affiliation>
    <investigator_full_name>Dieter Buchheidt</investigator_full_name>
    <investigator_title>Professor Dr. Dieter Buchheidt</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspergillosis</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/NCT01695499
org study id: BAL-Biomarker-ICU Study
secondary id: Grant Pfizer ASPIRE Award
nct id: NCT01695499
lead sponsor: 
collaborator: 
has dmc: No
The aim of this project is therefore to explore on the clinical significance of analyzing
      surrogate markers combined with conventional diagnostics in the ICU setting. BAL, blood and
      biopsy samples will be subjected to a combined analysis of GM, BDG, Aspergillus specific PCR
      assays in addition to conventional diagnostics (Microscopy, Culture,Histology) for ICU pts
      with pulmonary infiltrates.

      As GM and BDG are not species-specific, three established and repeatedly published species
      specific PCR-based assays (nested PCR, real time PCR assay, multifungal DNA Array)developed
      by our group will be investigated in combination with the serological tests in a multicenter
      prospective clinical diagnostic trial.
observational model: Cohort
time perspective: Prospective
measure: Diagnostic accuracy of combined biomarker testing in BAL fluid in relation to diagnostic certainty
time frame: 6 weeks
description: Evaluation of diagnostic accuracy of the combined biomarker approach
arm group label: Immunosuppressed ICU Patients with lung infiltrates
description: Immunosuppressed ICU Patients with lung infiltrates
arm group label: Control Group
description: BAL and blood aliquots of 20 immunocompetent pts (suffering from lung diseases) will be collected and tested identically as a control population.
Only fungal DNA investigated
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: Germany
citation: Reinwald M, Hummel M, Kovalevskaya E, Spiess B, Heinz WJ, Vehreschild JJ, Schultheis B, Krause SW, Claus B, Suedhoff T, Schwerdtfeger R, Reuter S, Kiehl MG, Hofmann WK, Buchheidt D. Therapy with antifungals decreases the diagnostic performance of PCR for diagnosing invasive aspergillosis in bronchoalveolar lavage samples of patients with haematological malignancies. J Antimicrob Chemother. 2012 Sep;67(9):2260-7. doi: 10.1093/jac/dks208. Epub 2012 Jun 27.
PMID: 22740590
citation: Reinwald M, Spiess B, Heinz WJ, Vehreschild JJ, Lass-Florl C, Kiehl M, Schultheis B, Krause SW, Wolf HH, Bertz H, Maschmeyer G, Hofmann WK, Buchheidt D. Diagnosing pulmonary aspergillosis in patients with hematological malignancies: a multicenter prospective evaluation of an Aspergillus PCR assay and a galactomannan ELISA in bronchoalveolar lavage samples. Eur J Haematol. 2012 Aug;89(2):120-7. doi: 10.1111/j.1600-0609.2012.01806.x. Epub 2012 Jun 22.
PMID: 22650156
citation: Spiess B, Seifarth W, Merker N, Howard SJ, Reinwald M, Dietz A, Hofmann WK, Buchheidt D. Development of novel PCR assays to detect azole resistance-mediating mutations of the Aspergillus fumigatus cyp51A gene in primary clinical samples from neutropenic patients. Antimicrob Agents Chemother. 2012 Jul;56(7):3905-10. doi: 10.1128/AAC.05902-11. Epub 2012 Apr 23.
PMID: 22526309
responsible party type: Principal Investigator
investigator affiliation: Heidelberg University
investigator full name: Dieter Buchheidt
investigator title: Professor Dr. Dieter Buchheidt
mesh term: Aspergillosis