<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/NCT04434209</url>
  </required_header>
  <id_info>
    <org_study_id>LAPIS</org_study_id>
    <nct_id>NCT04434209</nct_id>
  </id_info>
  <brief_title>A Study Looking at the Use of Biomarkers to Provide Early Indication of Acute Kidney Injury in Patients With Sepsis (Limiting AKI Progression In Sepsis)</brief_title>
  <acronym>LAPIS</acronym>
  <official_title>Limiting AKI Progression In Sepsis (LAPIS): A Phase 4, Multicenter, Randomized Controlled Trial of Biomarker-guided Delivery of Kidney-sparing Care Measures in Sepsis Subjects at Risk of Developing AKI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioMérieux</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioMérieux</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Biomarkers that provide an early indicator of kidney stress could be useful in clinical&#xD;
      practice to detect silent episodes of acute kidney injury (AKI) or for early identification&#xD;
      of subjects at risk of AKI. Two urinary biomarkers have been identified as early indicators&#xD;
      of AKI. The NephroCheck® test is a commercially available test that uses these biomarkers,&#xD;
      and this study assesses the use of these in reducing negative clinical outcomes for patients&#xD;
      with sepsis-associated AKI. The study will enroll subjects diagnosed with sepsis, including&#xD;
      septic shock, who will be randomly assigned to either receive NephroCheck®-guided&#xD;
      kidney-sparing and fast-tracking interventions; or to receive current Standard of Care&#xD;
      assessment and treatment.&#xD;
&#xD;
      NOTE: Participants are no longer being recruited to this study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Highly improbable to reach recruitment objective due to impact of COVID-19 pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">January 19, 2021</start_date>
  <completion_date type="Actual">February 14, 2022</completion_date>
  <primary_completion_date type="Actual">February 14, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of deaths, dialysis or progression of AKI</measure>
    <time_frame>Enrollment to 72 hours</time_frame>
    <description>Measured by composite number of deaths, dialysis or progression of AKI. Dialysis defined as any form of renal replacement therapy (RRT); progression of AKI defined as Stage 0 to 2/3 or Stage 1 to 3.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with progression of AKI</measure>
    <time_frame>Enrollment to 48 and 72 hours</time_frame>
    <description>Progression of AKI (Acute Kidney Injury) to Stage 2 or 3 during the time frame. Measured independently.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of deaths</measure>
    <time_frame>Enrollment to 48 and 72 hours</time_frame>
    <description>Number of deaths. Measured independently.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants receiving dialysis</measure>
    <time_frame>Enrollment to 48 and 72 hours</time_frame>
    <description>Dialysis defined as any form of renal replacement therapy (RRT). Measured independently.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number participants at Stage 2 or 3 AKI</measure>
    <time_frame>Enrollment to 72 hours</time_frame>
    <description>Defined as highest stage of AKI during the time frame</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>Enrollment to hospital discharge or Day 60, whichever is sooner</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Sepsis</condition>
  <condition>Acute Kidney Injury</condition>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>NephroCheck-guided interventions</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of Care assessment and treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Subject management guided by NephroCheck® test</intervention_name>
    <description>NephroCheck® is a device using biomarkers to identify subjects at risk of sepsis-associated acute kidney injury</description>
    <arm_group_label>NephroCheck-guided interventions</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of Care patient management</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of sepsis or septic shock.&#xD;
&#xD;
          -  Admission to the ICU or planned admission to the ICU with an expected stay of 72 hours&#xD;
             or more after enrollment in the same hospital.&#xD;
&#xD;
          -  Expected to have indwelling urinary catheter placed and kept until at least 48 hours&#xD;
             after enrollment.&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with known pregnancy, prisoners or institutionalized individuals.&#xD;
&#xD;
          -  Previous renal transplant.&#xD;
&#xD;
          -  Stage 2 or 3 Acute Kidney Injury (AKI) at screening.&#xD;
&#xD;
          -  Receiving dialysis (either acute or chronic), or in imminent need of dialysis at&#xD;
             enrollment.&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt; 45 mL/min/1.73 m2.&#xD;
&#xD;
          -  Known End Stage Renal Disease (ESRD) or history of active nephrotic syndrome within&#xD;
             the last 3 months.&#xD;
&#xD;
          -  Known Stage 2-3 AKI within last 2 weeks.&#xD;
&#xD;
          -  Terminally ill (defined as expectation of death within 6 months), has a do not&#xD;
             resuscitate order that would restrict protocol-required procedures, or is being&#xD;
             admitted only for palliative care.&#xD;
&#xD;
          -  History of solid organ transplant and receiving calcineurin inhibitors.&#xD;
&#xD;
          -  Documented serious allergy (i.e. anaphylaxis) to vancomycin, aminoglycosides,&#xD;
             penicillins, or cephalosporins (intravenous or oral).&#xD;
&#xD;
          -  Known current serum total bilirubin &gt; 4mg/dL.&#xD;
&#xD;
          -  Subjects already included in an observational study can be co-enrolled in LAPIS.&#xD;
             Subjects already included in an interventional study may be enrolled with pre-approval&#xD;
             of the sponsor according to the following rules:&#xD;
&#xD;
               1. Co-enrollment in LAPIS will not be allowed with investigational drug and device&#xD;
                  studies;&#xD;
&#xD;
               2. Studies may be allowed if AKI or kidney function is not an endpoint with&#xD;
                  pre-approval of the LAPIS sponsor;&#xD;
&#xD;
               3. Co-enrollment in LAPIS will not be allowed if co-enrollment is an exclusion&#xD;
                  criterion in the other study.&#xD;
&#xD;
          -  Subjects with laboratory confirmed COVID-19 infection as the primary reason for&#xD;
             hospital admission.&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hernando Gomez, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Critical Care Nephrology, University of Pittsburgh Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>LSU Health Sciences Center, 1541 Kings Highway</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Womens Hospital, 75 Francis Street</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center, 1275 York Avenue</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Sint-Jan Brugge-Oostende, Intensieve Zorgen, Ruddershove 10</name>
      <address>
        <city>Brugge</city>
        <state>West-Vlaanderen</state>
        <zip>8000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Erasme, Soins Intensifs, Route de Lennik 808</name>
      <address>
        <city>Bruxelles</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Angers, 4 Rue Larrey</name>
      <address>
        <city>Angers</city>
        <state>Maine-et-Loire</state>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Béthune, Service de Réanimation et Surveillance continue, 27 rue Delbecque</name>
      <address>
        <city>Béthune</city>
        <state>Pas-de-Calais</state>
        <zip>62408</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Dijon Complexe Du Bocage, Department Infectiologie, 14 rue Gaffarel</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cochin, 27 Rue Du Faubourg Saint Jacques</name>
      <address>
        <city>Paris</city>
        <zip>75679</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinic Heidelberg, Klinik für Anaesthesiologie, Im Neuenheimer Feld 110</name>
      <address>
        <city>Heidelberg</city>
        <state>Baden-Württemberg</state>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Leipzig, Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Liebigstraße 20</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Munster, Albert-Schweitzer-Campus 1</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>February 28, 2022</last_update_submitted>
  <last_update_submitted_qc>February 28, 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>
  <keyword>Sepsis</keyword>
  <keyword>Acute Kidney Injury</keyword>
  <keyword>Kidney damage</keyword>
  <keyword>Septic shock</keyword>
  <keyword>Biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Shock, Septic</mesh_term>
    <mesh_term>Acute Kidney Injury</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/NCT04434209
org study id: LAPIS
nct id: NCT04434209
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
Biomarkers that provide an early indicator of kidney stress could be useful in clinical
      practice to detect silent episodes of acute kidney injury (AKI) or for early identification
      of subjects at risk of AKI. Two urinary biomarkers have been identified as early indicators
      of AKI. The NephroCheck® test is a commercially available test that uses these biomarkers,
      and this study assesses the use of these in reducing negative clinical outcomes for patients
      with sepsis-associated AKI. The study will enroll subjects diagnosed with sepsis, including
      septic shock, who will be randomly assigned to either receive NephroCheck®-guided
      kidney-sparing and fast-tracking interventions; or to receive current Standard of Care
      assessment and treatment.

      NOTE: Participants are no longer being recruited to this study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Participant)
measure: Number of deaths, dialysis or progression of AKI
time frame: Enrollment to 72 hours
description: Measured by composite number of deaths, dialysis or progression of AKI. Dialysis defined as any form of renal replacement therapy (RRT); progression of AKI defined as Stage 0 to 2/3 or Stage 1 to 3.
measure: Number of participants with progression of AKI
time frame: Enrollment to 48 and 72 hours
description: Progression of AKI (Acute Kidney Injury) to Stage 2 or 3 during the time frame. Measured independently.
measure: Number of deaths
time frame: Enrollment to 48 and 72 hours
description: Number of deaths. Measured independently.
measure: Number of participants receiving dialysis
time frame: Enrollment to 48 and 72 hours
description: Dialysis defined as any form of renal replacement therapy (RRT). Measured independently.
measure: Number participants at Stage 2 or 3 AKI
time frame: Enrollment to 72 hours
description: Defined as highest stage of AKI during the time frame
measure: ICU length of stay
time frame: Enrollment to hospital discharge or Day 60, whichever is sooner
arm group label: NephroCheck-guided interventions
arm group type: Experimental
arm group label: Standard of Care
arm group type: Active Comparator
description: Standard of Care assessment and treatment
intervention type: Device
intervention name: Subject management guided by NephroCheck® test
description: NephroCheck® is a device using biomarkers to identify subjects at risk of sepsis-associated acute kidney injury
arm group label: NephroCheck-guided interventions
intervention type: Other
intervention name: Standard of Care
description: Standard of Care patient management
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Hernando Gomez, MD, MPH
role: Principal Investigator
affiliation: Center for Critical Care Nephrology, University of Pittsburgh Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: France
country: Germany
country: United States
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Shock, Septic
mesh term: Acute Kidney Injury