<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/NCT03004950</url>
  </required_header>
  <id_info>
    <org_study_id>PRO16090669</org_study_id>
    <secondary_id>R01DK106256-01A1</secondary_id>
    <nct_id>NCT03004950</nct_id>
  </id_info>
  <brief_title>Biomarker Effectiveness Analysis in Contrast Nephropathy (BEACON)</brief_title>
  <official_title>Biomarker Effectiveness Analysis in Contrast Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>US Department of Veterans Affairs</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is an observational non-interventional study which will examine a) the accuracy of&#xD;
      biomarkers in predicting renal and cardiovascular outcomes after contrast-induced acute&#xD;
      kidney injury.&#xD;
&#xD;
      This study will obtain de-identified human plasma &amp; urine samples and corresponding&#xD;
      de-identified research study data on subjects who are enrolled into the Prevention of Serious&#xD;
      Adverse Events Following Angiography (PRESERVE) study and Biomarker Collection and Analysis&#xD;
      in the PRESERVE Trial (VA CSP #578). Biomarker analyses will be performed on the&#xD;
      de-identified samples and merged with de-identified research study data.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Contrast-induced acute kidney injury (CIAKI) is a serious complication occurring in patients&#xD;
      with chronic kidney disease undergoing angiography and is associated with adverse renal and&#xD;
      cardiovascular outcomes. The investigators will address two key questions that remain in&#xD;
      high-risk patients undergoing angiography. First, early detection of CIAKI after contrast&#xD;
      exposure is problematic because rise in serum creatinine or decline in urine output occur&#xD;
      over several days and many cases are under-diagnosed. Second, early risk stratification for&#xD;
      long-term adverse events is also problematic because existing risk prediction models only&#xD;
      have a modest predictive value. Availability of a biomarker that detects subclinical CIAKI&#xD;
      before creatinine and also aids in risk stratification will change primary and secondary&#xD;
      prevention strategies. The FDA has recently approved two novel, highly sensitive, urinary&#xD;
      cell cycle arrest biomarkers for early detection of AKI. The investigators have shown that&#xD;
      these biomarkers: tissue inhibitor of metalloproteinase (TIMP)-2 and insulin growth factor&#xD;
      binding protein (IGFBP)7, detect AKI before serum creatinine in critically ill patients and&#xD;
      are associated with long-term adverse outcomes. Whether these markers can be used to predict&#xD;
      renal and cardiovascular outcomes in patients undergoing angiography is yet unknown. The&#xD;
      investigators have been recently funded by the Department of Veterans Affairs to conduct a&#xD;
      multicenter, randomized, clinical trial in 7,680 high-risk patients undergoing angiography to&#xD;
      compare the effectiveness of intravenous sodium bicarbonate with isotonic sodium chloride,&#xD;
      and oral N- acetylcysteine with placebo, for the prevention of serious adverse outcomes&#xD;
      associated with CIAKI. The NIDDK has funded an associated biorepository to examine known and&#xD;
      yet-to-be identified biomarkers for CIAKI. The investigators propose to leverage these&#xD;
      resources to conduct an ancillary observational study entitled Biomarker Effectiveness&#xD;
      Analysis in Contrast Nephropathy (BEACON). Using urine and plasma samples obtained before and&#xD;
      at four hours after angiography in 1,100 subjects, the investigators will address two&#xD;
      specific aims. Aim 1 will examine the accuracy of urinary TIMP-2, IGFBP7, and select other&#xD;
      plasma biomarkers in predicting the composite renal outcome of death, dialysis dependence, or&#xD;
      persistent renal injury at day 90 after contrast exposure (Aim 1a); biomarker&#xD;
      reclassification of risk for adverse renal outcomes and develop a risk score (Aim 1b); and&#xD;
      predicting the progression of chronic kidney disease (Aim 1c). Aim 2 will examine the&#xD;
      accuracy of urinary TIMP-2 and IGFBP7 in predicting the composite outcome of hospitalization&#xD;
      with acute coronary syndrome; heart failure; cerebrovascular accident; or all-cause mortality&#xD;
      within 90 days (Aim 2a); and biomarker reclassification of risk for cardiovascular events&#xD;
      (Aim 2b). The proposed work will advance NIDDK's mission of early detection,&#xD;
      risk-stratification, and prognostication of CIAKI. It will provide new scientific knowledge&#xD;
      on using biomarkers to monitor patients undergoing angiography and will have a high impact on&#xD;
      clinical practice, physicians, and policy makers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">February 28, 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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Predicting the composite renal outcome of death, dialysis dependence, or persistent renal injury, biomarker reclassification of risk for adverse renal outcomes and develop a risk score, and predicting the progression of chronic kidney disease</measure>
    <time_frame>Day 90 after contrast exposure</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>urinary biomarkers in predicting the composite outcome of hospitalization with acute coronary syndrome; heart failure; cerebrovascular accident; or all-cause mortality within 90 days,</measure>
    <time_frame>Within 90 days</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">922</enrollment>
  <condition>Acute Renal Failure</condition>
  <condition>Kidney Diseases</condition>
  <condition>Chronic Kidney Disease</condition>
  <condition>Coronary (Artery); Disease</condition>
  <eligibility>
    <study_pop>
      <textblock>
        1,100 men and women enrolled into the PRESERVE trial (NCT01467466)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Planned elective or urgent coronary or non-coronary angiography with iodinated&#xD;
             contrast media in which it is anticipated that there will be an interval of ≥3 hours&#xD;
             between the identification of the indication for angiography and the time of the&#xD;
             planned procedure&#xD;
&#xD;
          -  Pre-angiography eGFR &lt;60 ml/min/1.73 m2 with diabetes mellitus or pre-angiography eGFR&#xD;
             &lt;45 ml/min/1.73 m2 with or without diabetes mellitus&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently receiving hemodialysis, peritoneal dialysis, continuous renal replacement&#xD;
             therapy, or slow low efficiency dialysis&#xD;
&#xD;
          -  Stage 5 chronic kidney disease (eGFR &lt;15 mL/min/1.73 m2)&#xD;
&#xD;
          -  Unstable baseline serum creatinine (if known) at the time of angiography defined by a&#xD;
             change in serum creatinine of ≥25% over the 3 days prior to angiography&#xD;
&#xD;
          -  Decompensated heart failure requiring any of the following therapies at the time of&#xD;
             angiography&#xD;
&#xD;
          -  Emergent angiography procedures defined as an anticipated duration of &lt;3 hours between&#xD;
             the identification of the indication for angiography and the time of the planned&#xD;
             procedure. We are excluding these patients due to the limited time to collect&#xD;
             necessary research data and to ensure that research procedures do not interfere with&#xD;
             clinical care&#xD;
&#xD;
          -  Receipt of intravascular iodinated contrast within the 7 days preceding angiography&#xD;
&#xD;
          -  Receipt of oral or IV NAC within the 48 hours preceding angiography&#xD;
&#xD;
          -  Known allergy to NAC&#xD;
&#xD;
          -  Known allergy to iodinated contrast media&#xD;
&#xD;
          -  Age &lt;18 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prisoner&#xD;
&#xD;
          -  Ongoing participation in a concurrent interventional study&#xD;
&#xD;
          -  Eligible patients who indicate at the time of recruitment an unwillingness to comply&#xD;
             with the 96-hour and 90-day outcome assessments&#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>Raghavan Murugan, MD, MS, FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>March 29, 2023</last_update_submitted>
  <last_update_submitted_qc>March 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Raghavan Murugan</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03004950
org study id: PRO16090669
secondary id: R01DK106256-01A1
nct id: NCT03004950
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
This study is an observational non-interventional study which will examine a) the accuracy of
      biomarkers in predicting renal and cardiovascular outcomes after contrast-induced acute
      kidney injury.

      This study will obtain de-identified human plasma & urine samples and corresponding
      de-identified research study data on subjects who are enrolled into the Prevention of Serious
      Adverse Events Following Angiography (PRESERVE) study and Biomarker Collection and Analysis
      in the PRESERVE Trial (VA CSP #578). Biomarker analyses will be performed on the
      de-identified samples and merged with de-identified research study data.
Contrast-induced acute kidney injury (CIAKI) is a serious complication occurring in patients
      with chronic kidney disease undergoing angiography and is associated with adverse renal and
      cardiovascular outcomes. The investigators will address two key questions that remain in
      high-risk patients undergoing angiography. First, early detection of CIAKI after contrast
      exposure is problematic because rise in serum creatinine or decline in urine output occur
      over several days and many cases are under-diagnosed. Second, early risk stratification for
      long-term adverse events is also problematic because existing risk prediction models only
      have a modest predictive value. Availability of a biomarker that detects subclinical CIAKI
      before creatinine and also aids in risk stratification will change primary and secondary
      prevention strategies. The FDA has recently approved two novel, highly sensitive, urinary
      cell cycle arrest biomarkers for early detection of AKI. The investigators have shown that
      these biomarkers: tissue inhibitor of metalloproteinase (TIMP)-2 and insulin growth factor
      binding protein (IGFBP)7, detect AKI before serum creatinine in critically ill patients and
      are associated with long-term adverse outcomes. Whether these markers can be used to predict
      renal and cardiovascular outcomes in patients undergoing angiography is yet unknown. The
      investigators have been recently funded by the Department of Veterans Affairs to conduct a
      multicenter, randomized, clinical trial in 7,680 high-risk patients undergoing angiography to
      compare the effectiveness of intravenous sodium bicarbonate with isotonic sodium chloride,
      and oral N- acetylcysteine with placebo, for the prevention of serious adverse outcomes
      associated with CIAKI. The NIDDK has funded an associated biorepository to examine known and
      yet-to-be identified biomarkers for CIAKI. The investigators propose to leverage these
      resources to conduct an ancillary observational study entitled Biomarker Effectiveness
      Analysis in Contrast Nephropathy (BEACON). Using urine and plasma samples obtained before and
      at four hours after angiography in 1,100 subjects, the investigators will address two
      specific aims. Aim 1 will examine the accuracy of urinary TIMP-2, IGFBP7, and select other
      plasma biomarkers in predicting the composite renal outcome of death, dialysis dependence, or
      persistent renal injury at day 90 after contrast exposure (Aim 1a); biomarker
      reclassification of risk for adverse renal outcomes and develop a risk score (Aim 1b); and
      predicting the progression of chronic kidney disease (Aim 1c). Aim 2 will examine the
      accuracy of urinary TIMP-2 and IGFBP7 in predicting the composite outcome of hospitalization
      with acute coronary syndrome; heart failure; cerebrovascular accident; or all-cause mortality
      within 90 days (Aim 2a); and biomarker reclassification of risk for cardiovascular events
      (Aim 2b). The proposed work will advance NIDDK's mission of early detection,
      risk-stratification, and prognostication of CIAKI. It will provide new scientific knowledge
      on using biomarkers to monitor patients undergoing angiography and will have a high impact on
      clinical practice, physicians, and policy makers.
observational model: Cohort
time perspective: Retrospective
measure: Predicting the composite renal outcome of death, dialysis dependence, or persistent renal injury, biomarker reclassification of risk for adverse renal outcomes and develop a risk score, and predicting the progression of chronic kidney disease
time frame: Day 90 after contrast exposure
measure: urinary biomarkers in predicting the composite outcome of hospitalization with acute coronary syndrome; heart failure; cerebrovascular accident; or all-cause mortality within 90 days,
time frame: Within 90 days
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Raghavan Murugan, MD, MS, FRCP
role: Principal Investigator
affiliation: University of Pittsburgh
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Raghavan Murugan
investigator title: M.D.
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Acute Kidney Injury
mesh term: Coronary Artery Disease
mesh term: Coronary Disease
sharing ipd: No