<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/NCT04408248</url>
  </required_header>
  <id_info>
    <org_study_id>283675</org_study_id>
    <nct_id>NCT04408248</nct_id>
  </id_info>
  <brief_title>AKI Biomarkers in Coronavirus(COVID)-19</brief_title>
  <official_title>AKI Biomarkers for Prediction of Acute Kidney Injury in Critically Ill Patients With COVID-19 and Respiratory Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital Muenster</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Guy's and St Thomas' NHS Foundation Trust</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>
      This research aims to investigate the role of daily measurement of urinary cell cycle arrest&#xD;
      markers and other serum and urinary biomarkers to predict the development of acute kidney&#xD;
      injury in critically ill patients with COVID-19 and acute respiratory disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients requiring&#xD;
      admission to an intensive care unit. In critically ill patients with COVID-19, acute&#xD;
      respiratory disease and acute kidney injury (AKI) are very common. Patients with AKI have an&#xD;
      increased risk of mortality, especially renal replacement therapy (RRT) is required. The&#xD;
      latest Intensive Care National Audit &amp; Research Centre (ICNARC) report shows a 77% ICU&#xD;
      mortality in patients with COVID-19 who require mechanical ventilation and RRT.&#xD;
&#xD;
      COVID-19 associated AKI is still poorly understood. The exact underlying pathophysiology&#xD;
      remains unknown. Furthermore, there are no specific strategies to prevent or treat AKI.&#xD;
      Management is supportive consisting of fluid and haemodynamic optimization, discontinuation&#xD;
      of nephrotoxic drugs and prevention of nephrotoxic exposures. Ideally, AKI needs to be&#xD;
      recognized as early as possible for these supportive measures to be effective.&#xD;
&#xD;
      Early prediction of AKI may be valuable to optimize management and improve outcomes. In&#xD;
      critically ill patients without COVID-19, the two cell-cycle arrest markers, tissue inhibitor&#xD;
      of metalloproteinases-2 (TIMP-2) and insulin-like growth-factor binding protein 7 (IGFBP7),&#xD;
      have been shown to predict the development of AKI. Whether these new biomarkers also predict&#xD;
      the development of AKI in critically ill patients with COVID-19 is unknown.&#xD;
&#xD;
      The aim of this project is to explore whether urinary cell cycle arrest markers and other&#xD;
      renal biomarkers have a role in predicting AKI in critically ill patients with COVID-19 and&#xD;
      acute respiratory disease. The results will advance the understanding of this disease and&#xD;
      serve to develop strategies for individualized management of this high-risk group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 20, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>Any stage of acute kidney injury</measure>
    <time_frame>7 days</time_frame>
    <description>As defined by Kidney Diseases: Improving Global Outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>need for RRT in first 7 days</measure>
    <time_frame>7 days</time_frame>
    <description>Renal replacement therapy requirement at the clinicians' discretion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>7 and 28 days</time_frame>
    <description>ICU mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>7 and 28 days</time_frame>
    <description>Duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of vasopressor support</measure>
    <time_frame>7 and 28 days</time_frame>
    <description>Duration</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>COVID</condition>
  <condition>Acute Respiratory Failure</condition>
  <condition>Acute Kidney Injury</condition>
  <arm_group>
    <arm_group_label>COVID-19 patients with acute respiratory disease</arm_group_label>
    <description>Adult patients with COVID-19 and moderate or severe respiratory disease</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The investigators will collect blood and urine samples for biomarker measurement at the&#xD;
      following time points: at the time point of study inclusion, 12h, 24h, 36h, 48h, 60h, and 72h&#xD;
      after inclusion.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        COVID-19 patients with moderate or severe respiratory disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Moderate or severe respiratory disease as defined by Berlin criteria&#xD;
&#xD;
          2. COVID-19 positive&#xD;
&#xD;
          3. Age ≥ 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. pre-existing AKI&#xD;
&#xD;
          2. severe chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR)&#xD;
             &lt;20ml/min&#xD;
&#xD;
          3. end-stage renal failure on regular dialysis&#xD;
&#xD;
          4. kidney transplant within the last 12 months&#xD;
&#xD;
          5. pregnancy&#xD;
&#xD;
          6. breastfeeding&#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>Marlies Ostermann, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guy's and St Thomas' NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marlies Ostermann, MD, PhD</last_name>
    <phone>0044 207 188 3038</phone>
    <phone_ext>83036</phone_ext>
    <email>Marlies.Ostermann@gstt.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nuttha Lumlertgul, MD, PhD</last_name>
    <phone>0044 207 188 3038</phone>
    <phone_ext>83036</phone_ext>
    <email>Nuttha.Lumlertgul@gstt.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Guy's &amp; St Thomas' Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marlies Ostermann, MD, PhD</last_name>
      <phone>020 71883038</phone>
      <email>Marlies.Ostermann@gstt.nhs.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04408248
org study id: 283675
nct id: NCT04408248
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This research aims to investigate the role of daily measurement of urinary cell cycle arrest
      markers and other serum and urinary biomarkers to predict the development of acute kidney
      injury in critically ill patients with COVID-19 and acute respiratory disease.
COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients requiring
      admission to an intensive care unit. In critically ill patients with COVID-19, acute
      respiratory disease and acute kidney injury (AKI) are very common. Patients with AKI have an
      increased risk of mortality, especially renal replacement therapy (RRT) is required. The
      latest Intensive Care National Audit & Research Centre (ICNARC) report shows a 77% ICU
      mortality in patients with COVID-19 who require mechanical ventilation and RRT.

      COVID-19 associated AKI is still poorly understood. The exact underlying pathophysiology
      remains unknown. Furthermore, there are no specific strategies to prevent or treat AKI.
      Management is supportive consisting of fluid and haemodynamic optimization, discontinuation
      of nephrotoxic drugs and prevention of nephrotoxic exposures. Ideally, AKI needs to be
      recognized as early as possible for these supportive measures to be effective.

      Early prediction of AKI may be valuable to optimize management and improve outcomes. In
      critically ill patients without COVID-19, the two cell-cycle arrest markers, tissue inhibitor
      of metalloproteinases-2 (TIMP-2) and insulin-like growth-factor binding protein 7 (IGFBP7),
      have been shown to predict the development of AKI. Whether these new biomarkers also predict
      the development of AKI in critically ill patients with COVID-19 is unknown.

      The aim of this project is to explore whether urinary cell cycle arrest markers and other
      renal biomarkers have a role in predicting AKI in critically ill patients with COVID-19 and
      acute respiratory disease. The results will advance the understanding of this disease and
      serve to develop strategies for individualized management of this high-risk group.
observational model: Cohort
time perspective: Prospective
measure: Any stage of acute kidney injury
time frame: 7 days
description: As defined by Kidney Diseases: Improving Global Outcome
measure: need for RRT in first 7 days
time frame: 7 days
description: Renal replacement therapy requirement at the clinicians' discretion
measure: Mortality
time frame: 7 and 28 days
description: ICU mortality
measure: Duration of mechanical ventilation
time frame: 7 and 28 days
description: Duration
measure: Duration of vasopressor support
time frame: 7 and 28 days
description: Duration
arm group label: COVID-19 patients with acute respiratory disease
description: Adult patients with COVID-19 and moderate or severe respiratory disease
The investigators will collect blood and urine samples for biomarker measurement at the
      following time points: at the time point of study inclusion, 12h, 24h, 36h, 48h, 60h, and 72h
      after inclusion.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marlies Ostermann, MD, PhD
role: Principal Investigator
affiliation: Guy's and St Thomas' NHS Foundation Trust
last name: Marlies Ostermann, MD, PhD
phone: 0044 207 188 3038
phone ext: 83036
email: Marlies.Ostermann@gstt.nhs.uk
last name: Nuttha Lumlertgul, MD, PhD
phone: 0044 207 188 3038
phone ext: 83036
email: Nuttha.Lumlertgul@gstt.nhs.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Respiratory Insufficiency
mesh term: Acute Kidney Injury
sharing ipd: Undecided