<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/NCT01735162</url>
  </required_header>
  <id_info>
    <org_study_id>CIN001-AKI-CHERUB</org_study_id>
    <nct_id>NCT01735162</nct_id>
  </id_info>
  <brief_title>Study of the Prediction of Acute Kidney Injury in Children Using Risk Stratification and Biomarkers</brief_title>
  <acronym>AKI-CHERUB</acronym>
  <official_title>Prospective Study of Acute Kidney Injury in Critically Ill Children Predicted by Renal Angina and Urinary Biomarkers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute kidney injury (AKI) is a common clinical event with severe consequences. In the&#xD;
      pediatric intensive care unit (PICU), AKI occurs in almost 10% of all patients and evidence&#xD;
      suggests that children are dying not just with AKI, but from AKI. Unfortunately, the&#xD;
      treatment for AKI is limited to a great extent by delayed diagnosis. Reliance on markers of&#xD;
      kidney injury that change only when significant damage has already occurred has rendered&#xD;
      potential therapies ineffective. For this reason, identification of new markers of AKI that&#xD;
      change early in the course of injury is paramount. While new AKI biomarkers have been&#xD;
      identified, their performance in the general PICU population is variable. The investigators&#xD;
      recently proposed the concept of 'renal angina' as a way to risk stratify patients in the ICU&#xD;
      for AKI risk. In the AKI-CHERUB study, the investigators propose to study renal angina in&#xD;
      PICU patients alone and in combination with urinary biomarkers for AKI prediction. The&#xD;
      investigators hypothesize that renal angina will increase the predictive precision of urinary&#xD;
      biomarkers for AKI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Reliance on serum creatinine and urine output for diagnosis of acute kidney injury (AKI) has&#xD;
      limited the ability of potential therapeutic measures to be effective. The investigators'&#xD;
      recent proposition of the renal angina construct aims to improve and expedite AKI diagnosis&#xD;
      through use of risk stratification. An apt parallel is the profound outcome change that has&#xD;
      been effected in acute coronary syndrome through targeted troponin measurements in patients&#xD;
      with both risk factors and clinical symptoms of coronary ischemia. Novel AKI biomarkers will&#xD;
      struggle to gain widespread use until their performance in patients of varying degrees of AKI&#xD;
      risk can be balanced with their cost and availability. The investigators hypothesize risk&#xD;
      stratification using renal angina (ANG) identifies children at-risk vs. not at-risk for AKI,&#xD;
      focusing subsequent biomarker measurement to &quot;rule out&quot; AKI only in children with ANG,&#xD;
      increasing biomarker predictive precision. This study is significant because it represents&#xD;
      the next step in the vertical integration of AKI biomarkers into routine clinical practice to&#xD;
      guide their use rationally. The identification of at-risk patients to guide appropriate&#xD;
      biomarker use is high-impact because it will make implementation of preventive and supportive&#xD;
      therapies for AKI more effective; data from this study would serve to provide the indications&#xD;
      to the Food and Drug Administration (FDA) for biomarker use in critically ill children. The&#xD;
      study is innovative because it is the first prospective attempt to study the predictive&#xD;
      performance of biomarkers AKI in the PICU population using ANG stratification. The&#xD;
      investigators will observe all children admitted to the PICU with an expected length of stay&#xD;
      &gt; 48 hours. Urine will be collected from these children and levels of neutrophil gelatinase&#xD;
      associated lipocalin (NGAL), interleukin-18 (IL-18), liver-fatty acid binding protein&#xD;
      (l-FABP), and kidney injury molecule-1 (KIM-1) will be measured. Renal angina will be&#xD;
      assessed at time of admission. Primary outcome will be presence of AKI (as measured by Kidney&#xD;
      Diseases Improving Global Outcome (KDIGO) Class 2 or greater) at hospital day 3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">May 2013</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>Acute kidney injury</measure>
    <time_frame>At day 3 of PICU admission</time_frame>
    <description>Development of AKI by KDIGO Stage 2 criteria (Creatinine &gt; 200% baseline)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PICU length of stay</measure>
    <time_frame>60 days</time_frame>
    <description>Observational assessment of duration of length of stay in PICU from time of renal angina assessment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mortality</measure>
    <time_frame>60 day</time_frame>
    <description>Incidence of death within 60 days of ICU admission</description>
  </other_outcome>
  <other_outcome>
    <measure>Renal replacement therapy</measure>
    <time_frame>During ICU stay</time_frame>
    <description>We will use a dichotomization (yes/no) of whether renal replacement therapy was used in each patient until ICU discharge or death, whichever came first, followed up to 60 days</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">184</enrollment>
  <condition>Renal Angina</condition>
  <condition>Acute Kidney Injury</condition>
  <arm_group>
    <arm_group_label>Very high risk</arm_group_label>
    <description>Very high risk PICU patients are on mechanical ventilation and at least one inotrope or vasopressor at time of admission</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Risk</arm_group_label>
    <description>High risk PICU patients have a history of transplantation (solid organ or bone marrow)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate risk</arm_group_label>
    <description>Moderate risk PICU patients are all other admissions to the ICU (may have either mechanical ventilation or inotropy/vasopressor use but not both). Cannot have a history of transplant. Minimum expected stay 48 hours.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urinary samples, intended for discard so waiver of consent obtained. Urine samples spun and&#xD;
      frozen at -80C. Samples to be run for biomarker ELISA kits.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All children admitted to a tertiary children's hospital pediatric intensive care unit with&#xD;
        an expected length of stay &gt; 48 hours.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Minimum stay 48 hours&#xD;
&#xD;
          -  Indwelling urinary catheter&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of renal disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stuart Goldstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.cincinnatichildrens.org/service/c/cacn/default/</url>
    <description>Center for Acute Care Nephrology</description>
  </link>
  <reference>
    <citation>Goldstein SL. Acute kidney injury biomarkers: renal angina and the need for a renal troponin I. BMC Med. 2011 Dec 21;9:135. doi: 10.1186/1741-7015-9-135.</citation>
    <PMID>22189039</PMID>
  </reference>
  <reference>
    <citation>Basu RK, Chawla LS, Wheeler DS, Goldstein SL. Renal angina: an emerging paradigm to identify children at risk for acute kidney injury. Pediatr Nephrol. 2012 Jul;27(7):1067-78. doi: 10.1007/s00467-011-2024-5. Epub 2011 Oct 20.</citation>
    <PMID>22012033</PMID>
  </reference>
  <reference>
    <citation>Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol. 2010 May;5(5):943-9. doi: 10.2215/CJN.07201009. Epub 2010 Mar 18.</citation>
    <PMID>20299370</PMID>
  </reference>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>February 2, 2015</last_update_submitted>
  <last_update_submitted_qc>February 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital Medical Center, Cincinnati</investigator_affiliation>
    <investigator_full_name>Rajit Basu, MD, F.A.A.P.</investigator_full_name>
    <investigator_title>Director, Center for Acute Care Nephrology</investigator_title>
  </responsible_party>
  <keyword>Renal angina</keyword>
  <keyword>AKI</keyword>
  <keyword>Pediatric Intensive Care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Angina Pectoris</mesh_term>
    <mesh_term>Wounds and Injuries</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/NCT01735162
org study id: CIN001-AKI-CHERUB
nct id: NCT01735162
lead sponsor: 
has dmc: Yes
Acute kidney injury (AKI) is a common clinical event with severe consequences. In the
      pediatric intensive care unit (PICU), AKI occurs in almost 10% of all patients and evidence
      suggests that children are dying not just with AKI, but from AKI. Unfortunately, the
      treatment for AKI is limited to a great extent by delayed diagnosis. Reliance on markers of
      kidney injury that change only when significant damage has already occurred has rendered
      potential therapies ineffective. For this reason, identification of new markers of AKI that
      change early in the course of injury is paramount. While new AKI biomarkers have been
      identified, their performance in the general PICU population is variable. The investigators
      recently proposed the concept of 'renal angina' as a way to risk stratify patients in the ICU
      for AKI risk. In the AKI-CHERUB study, the investigators propose to study renal angina in
      PICU patients alone and in combination with urinary biomarkers for AKI prediction. The
      investigators hypothesize that renal angina will increase the predictive precision of urinary
      biomarkers for AKI.
Reliance on serum creatinine and urine output for diagnosis of acute kidney injury (AKI) has
      limited the ability of potential therapeutic measures to be effective. The investigators'
      recent proposition of the renal angina construct aims to improve and expedite AKI diagnosis
      through use of risk stratification. An apt parallel is the profound outcome change that has
      been effected in acute coronary syndrome through targeted troponin measurements in patients
      with both risk factors and clinical symptoms of coronary ischemia. Novel AKI biomarkers will
      struggle to gain widespread use until their performance in patients of varying degrees of AKI
      risk can be balanced with their cost and availability. The investigators hypothesize risk
      stratification using renal angina (ANG) identifies children at-risk vs. not at-risk for AKI,
      focusing subsequent biomarker measurement to "rule out" AKI only in children with ANG,
      increasing biomarker predictive precision. This study is significant because it represents
      the next step in the vertical integration of AKI biomarkers into routine clinical practice to
      guide their use rationally. The identification of at-risk patients to guide appropriate
      biomarker use is high-impact because it will make implementation of preventive and supportive
      therapies for AKI more effective; data from this study would serve to provide the indications
      to the Food and Drug Administration (FDA) for biomarker use in critically ill children. The
      study is innovative because it is the first prospective attempt to study the predictive
      performance of biomarkers AKI in the PICU population using ANG stratification. The
      investigators will observe all children admitted to the PICU with an expected length of stay
      > 48 hours. Urine will be collected from these children and levels of neutrophil gelatinase
      associated lipocalin (NGAL), interleukin-18 (IL-18), liver-fatty acid binding protein
      (l-FABP), and kidney injury molecule-1 (KIM-1) will be measured. Renal angina will be
      assessed at time of admission. Primary outcome will be presence of AKI (as measured by Kidney
      Diseases Improving Global Outcome (KDIGO) Class 2 or greater) at hospital day 3.
observational model: Cohort
time perspective: Prospective
measure: Acute kidney injury
time frame: At day 3 of PICU admission
description: Development of AKI by KDIGO Stage 2 criteria (Creatinine > 200% baseline)
measure: PICU length of stay
time frame: 60 days
description: Observational assessment of duration of length of stay in PICU from time of renal angina assessment
measure: Mortality
time frame: 60 day
description: Incidence of death within 60 days of ICU admission
measure: Renal replacement therapy
time frame: During ICU stay
description: We will use a dichotomization (yes/no) of whether renal replacement therapy was used in each patient until ICU discharge or death, whichever came first, followed up to 60 days
arm group label: Very high risk
description: Very high risk PICU patients are on mechanical ventilation and at least one inotrope or vasopressor at time of admission
arm group label: High Risk
description: High risk PICU patients have a history of transplantation (solid organ or bone marrow)
arm group label: Moderate risk
description: Moderate risk PICU patients are all other admissions to the ICU (may have either mechanical ventilation or inotropy/vasopressor use but not both). Cannot have a history of transplant. Minimum expected stay 48 hours.
Urinary samples, intended for discard so waiver of consent obtained. Urine samples spun and
      frozen at -80C. Samples to be run for biomarker ELISA kits.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Stuart Goldstein, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
country: United States
url: http://www.cincinnatichildrens.org/service/c/cacn/default/
description: Center for Acute Care Nephrology
citation: Goldstein SL. Acute kidney injury biomarkers: renal angina and the need for a renal troponin I. BMC Med. 2011 Dec 21;9:135. doi: 10.1186/1741-7015-9-135.
PMID: 22189039
citation: Basu RK, Chawla LS, Wheeler DS, Goldstein SL. Renal angina: an emerging paradigm to identify children at risk for acute kidney injury. Pediatr Nephrol. 2012 Jul;27(7):1067-78. doi: 10.1007/s00467-011-2024-5. Epub 2011 Oct 20.
PMID: 22012033
citation: Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol. 2010 May;5(5):943-9. doi: 10.2215/CJN.07201009. Epub 2010 Mar 18.
PMID: 20299370
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital Medical Center, Cincinnati
investigator full name: Rajit Basu, MD, F.A.A.P.
investigator title: Director, Center for Acute Care Nephrology
mesh term: Acute Kidney Injury
mesh term: Angina Pectoris
mesh term: Wounds and Injuries