<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/NCT03754023</url>
  </required_header>
  <id_info>
    <org_study_id>BRAVA Study</org_study_id>
    <nct_id>NCT03754023</nct_id>
  </id_info>
  <brief_title>Biomarker Rule in/Out in Patients With Acute Diseases for Validation of AKI (BRAVA) Acute Kidney Injury</brief_title>
  <acronym>BRAVA</acronym>
  <official_title>The Potential Role of Biomarkers (Urine TIMP-IGFBP7) in Determining the Incidence of Acute Kidney Injury (AKI) in All-comers Patients Presenting to the Emergency Department With Acute Diseases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GREAT Network Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GREAT Network Italy</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The presence or development of AKI impacts on outcomes in patients presenting with acute&#xD;
      conditions to the ED. As a result, treating physicians are often concerned with the risk of&#xD;
      AKI and take such risk in consideration when making subsequent therapeutic and diagnostic&#xD;
      decisions which may result in delaying or withholding therapeutic measures in order to&#xD;
      prevent further kidney damage (i.e. avoid imaging studies with contrast media).&#xD;
&#xD;
      If clinicians could be informed early that a patient is at minimal risk for AKI, they could&#xD;
      deploy timely and optimal diagnostic and treatment procedures for the underlying disease of&#xD;
      the patient without major concerns for causing or exacerbating kidney damage&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with acute diseases, it is mandatory for ED Physicians to immediately detect the&#xD;
      presence of AKI or exclude; but unfortunately Serum creatinine (SCr) variations (based on&#xD;
      KDIGO or AKIN criteria), take 24 to 48 hours to manifest the presence of acute renal ongoing&#xD;
      damage. AKI is currently, infact, defined as an increase in SCr of 1.5-fold from baseline&#xD;
      within 24 to 48 hours, and decrease in diuresis from admission in hospitalization, using&#xD;
      KDIGO.&#xD;
&#xD;
      As consequence, similarly to other biomarkers, such as troponins in acute coronary syndrome&#xD;
      and D-dimer in pulmonary embolism, a laboratory test to rule in or rule out AKI is needed in&#xD;
      critical patients in ED and our primary objective would be to evaluate the role of urine&#xD;
      TIMP-IGFBP7 in this setting.&#xD;
&#xD;
      Primary Objective of the BRAVA Study would be to evaluate the role of the urine biomarkers&#xD;
      TIMP-IGFBP7 in predicting the occurrence of AKI in patients presenting to ED with different&#xD;
      acute diseases and need for hospitalization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Actual">November 30, 2019</completion_date>
  <primary_completion_date type="Actual">June 30, 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>Diagnostic performance of urine TIMP-IGFBP7 as early biomarker in ruling in or ruling out acute kidney damage in patients presenting to ED with acute diseases.</measure>
    <time_frame>48 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall length in days of hospital stay</measure>
    <time_frame>30 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of chronic kidney disease (CKD)</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall mortality</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional (different countries in Asia Pacific Region) incidence of AKI in a cohort of patients presenting to the ED with acute diseases</measure>
    <time_frame>48 hours</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">818</enrollment>
  <condition>Acute Kidney Injury</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Urine-TIMP-IGFBP7 biomarker for AKI</intervention_name>
    <description>Urine-TIMP-IGFBP7 biomarker for AKI</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients presenting to the ED who are determined to be at high risk for AKI.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Patient Inclusion Criteria&#xD;
&#xD;
          -  Age ≥ 21 years&#xD;
&#xD;
          -  &gt;30% risk of developing AKI based on treating physicians' clinical evaluation AND/OR&#xD;
             Presence of ONE OF the following conditions:&#xD;
&#xD;
          -  Suspected or confirmed sepsis.&#xD;
&#xD;
          -  Acute decompensated heart failure.&#xD;
&#xD;
          -  Prolonged gastrointestinal losses from vomiting or diarrhea&#xD;
&#xD;
          -  Major trauma&#xD;
&#xD;
          -  Major bleeding (e.g. gastrointestinal, pulmonary, genitourinary)&#xD;
&#xD;
          -  Severe burns&#xD;
&#xD;
          -  Diabetic crisis (DKA, HHS)&#xD;
&#xD;
          -  Decompensated liver cirrhosis&#xD;
&#xD;
          -  Acute coronary syndrome&#xD;
&#xD;
          -  Emergent need for iodinated contrast studies&#xD;
&#xD;
          -  Shock from any cause&#xD;
&#xD;
        Patient Exclusion Criteria&#xD;
&#xD;
          -  Age &lt; 21 years.&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  Undergoing hemodialysis or peritoneal dialysis&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Terminal illness with &lt; 6 months prognosis&#xD;
&#xD;
          -  Do-not-resuscitate status&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Salvatore Di Somma</last_name>
    <role>Study Director</role>
    <affiliation>GREAT Network Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Sidney</city>
        <zip>NSW2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yashoda Hospital</name>
      <address>
        <city>Hyderabad</city>
        <zip>500003</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Konkuk University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05030</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhamathibody Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>India</country>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Thailand</country>
  </location_countries>
  <reference>
    <citation>Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and diagnostic workup. Crit Care. 2016 Sep 27;20(1):299. doi: 10.1186/s13054-016-1478-z.</citation>
    <PMID>27670788</PMID>
  </reference>
  <reference>
    <citation>Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.</citation>
    <PMID>26162677</PMID>
  </reference>
  <reference>
    <citation>Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, Brauer A, Moerer O. Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery? Crit Care. 2015 Jan 6;19(1):3. doi: 10.1186/s13054-014-0717-4.</citation>
    <PMID>25560277</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>March 8, 2021</last_update_submitted>
  <last_update_submitted_qc>March 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AKI</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Urine TIMP-IGFBP7</keyword>
  <keyword>Emergency Department</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Acute Disease</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to make IPD available</ipd_description>
  </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/NCT03754023
org study id: BRAVA Study
nct id: NCT03754023
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The presence or development of AKI impacts on outcomes in patients presenting with acute
      conditions to the ED. As a result, treating physicians are often concerned with the risk of
      AKI and take such risk in consideration when making subsequent therapeutic and diagnostic
      decisions which may result in delaying or withholding therapeutic measures in order to
      prevent further kidney damage (i.e. avoid imaging studies with contrast media).

      If clinicians could be informed early that a patient is at minimal risk for AKI, they could
      deploy timely and optimal diagnostic and treatment procedures for the underlying disease of
      the patient without major concerns for causing or exacerbating kidney damage
In patients with acute diseases, it is mandatory for ED Physicians to immediately detect the
      presence of AKI or exclude; but unfortunately Serum creatinine (SCr) variations (based on
      KDIGO or AKIN criteria), take 24 to 48 hours to manifest the presence of acute renal ongoing
      damage. AKI is currently, infact, defined as an increase in SCr of 1.5-fold from baseline
      within 24 to 48 hours, and decrease in diuresis from admission in hospitalization, using
      KDIGO.

      As consequence, similarly to other biomarkers, such as troponins in acute coronary syndrome
      and D-dimer in pulmonary embolism, a laboratory test to rule in or rule out AKI is needed in
      critical patients in ED and our primary objective would be to evaluate the role of urine
      TIMP-IGFBP7 in this setting.

      Primary Objective of the BRAVA Study would be to evaluate the role of the urine biomarkers
      TIMP-IGFBP7 in predicting the occurrence of AKI in patients presenting to ED with different
      acute diseases and need for hospitalization.
observational model: Cohort
time perspective: Prospective
measure: Diagnostic performance of urine TIMP-IGFBP7 as early biomarker in ruling in or ruling out acute kidney damage in patients presenting to ED with acute diseases.
time frame: 48 hours
measure: Overall length in days of hospital stay
time frame: 30 hours
measure: Incidence of chronic kidney disease (CKD)
time frame: 30 days
measure: Overall mortality
time frame: 30 days
measure: Regional (different countries in Asia Pacific Region) incidence of AKI in a cohort of patients presenting to the ED with acute diseases
time frame: 48 hours
intervention type: Diagnostic Test
intervention name: Urine-TIMP-IGFBP7 biomarker for AKI
description: Urine-TIMP-IGFBP7 biomarker for AKI
Urine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: No
last name: Salvatore Di Somma
role: Study Director
affiliation: GREAT Network Italy
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: India
country: Korea, Republic of
country: Singapore
country: Thailand
citation: Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and diagnostic workup. Crit Care. 2016 Sep 27;20(1):299. doi: 10.1186/s13054-016-1478-z.
PMID: 27670788
citation: Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
PMID: 26162677
citation: Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, Brauer A, Moerer O. Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery? Crit Care. 2015 Jan 6;19(1):3. doi: 10.1186/s13054-014-0717-4.
PMID: 25560277
responsible party type: Sponsor
mesh term: Acute Kidney Injury
mesh term: Acute Disease
mesh term: Wounds and Injuries
sharing ipd: No
ipd description: There is no plan to make IPD available