<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/NCT03765203</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00030299</org_study_id>
    <nct_id>NCT03765203</nct_id>
  </id_info>
  <brief_title>Utility of a Novel Dd-cfDNA Test to Detect Injury in Renal Post-Transplant Patients</brief_title>
  <acronym>QIDNEY</acronym>
  <official_title>Prospective, Randomized Controlled Trial Using CPV Vignettes to Assess the Clinical Utility of Natera Dd-cfDNA Test to Detect Allograft in Post-Transplant Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Qure Healthcare, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Natera, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Qure Healthcare, LLC</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Detecting allograft injury and rejection is critical to preventing graft loss. The current&#xD;
      standard of care (SoC) relies on serum creatinine (SC) and biopsy to monitor for and identify&#xD;
      kidney injury earlier. SC has poor specificity and sensitivity and response to rejection is&#xD;
      often delayed. Protocol biopsy is more accurate but involves the risk of complications. A&#xD;
      more definitive, less invasive method for monitoring injury and early rejection is needed.&#xD;
&#xD;
      We report on the clinical utility of donor-derived cell-free DNA (dd-cfDNA) in transplant&#xD;
      recipients' blood, measured using a novel SNP-based mmPCR NGS methodology, to diagnose&#xD;
      allograft injury/rejection. In this study, investigators will measure how use of dd-cfDNA&#xD;
      changes clinical practice.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Five-year kidney allograft survival rates are estimated to be as low as 71.6%. A leading&#xD;
      cause for the high prevalence of graft loss is the delay in detecting allograft injury from&#xD;
      active rejection, when early diagnosis and intervention presents the greatest chance of&#xD;
      preserving kidney function. Despite the frequent testing called for by care protocols, low&#xD;
      levels of injury can go undetected due to the low specificity and sensitivity of current,&#xD;
      standard testing methods: checking creatinine and immunosuppressive drug levels. More&#xD;
      definitive graft biopsies are an option, but they are invasive, expensive and can even put&#xD;
      the patient at risk for graft loss and other complications, making it undesirable as a&#xD;
      frequent monitoring test.&#xD;
&#xD;
      Donor-derived cell-free DNA (dd-cfDNA) detected in the blood of transplant recipients has&#xD;
      been shown to be a non-invasive diagnostic marker for allograft injury/rejection. Natera,&#xD;
      Inc. has recently developed a novel single nucleotide polymorphism (SNP)-based mmPCR NGS&#xD;
      methodology to measure dd-cfDNA in kidney transplant recipients for the detection of&#xD;
      allograft injury and rejection. As a growing leader in the diagnostic space, Natera has&#xD;
      commissioned a randomized controlled trial to determine the clinical utility of its dd-cfDNA&#xD;
      detection methodology for practicing nephrologists treating kidney allograft patients. This&#xD;
      study is expected to fill a gap in the evidence base on the clinical utility of dd-cfDNA&#xD;
      testing for allograft rejection.&#xD;
&#xD;
      The study is a pre-post, two round controlled trial of care practices in a nationally&#xD;
      representative sample of practicing nephrologists randomly assigned to a control or an&#xD;
      intervention arm. All participants will be asked to propose care for a total of 6 CPV&#xD;
      simulated patients who are adults aged 30-75; three or more months post-transplant; and&#xD;
      presenting with signs, symptoms and laboratory findings suggestive of allograft rejection.&#xD;
      Each assessment round will consist of 3 simulated patients. In between assessment rounds,&#xD;
      participants randomized into the intervention arm will receive educational materials on the&#xD;
      new allograft rejection test.&#xD;
&#xD;
      Investigators will assess whether practicing nephrologists more effectively identify and&#xD;
      manage patients with possible kidney allograft rejection when given access to Natera's novel&#xD;
      SNP-based mmPCR-NGS test that measures dd-cfDNA, and, whether those behavioral changes&#xD;
      improves patient management and optimizes resource utilization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2018</start_date>
  <completion_date type="Actual">January 7, 2019</completion_date>
  <primary_completion_date type="Actual">January 7, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>The study is a pre-post, two round controlled trial of care practices in a nationally representative sample of practicing nephrologists randomly assigned to a control or an intervention arm. All providers will be asked to propose care for a total of 6 CPV simulated patients who are adults aged 30-75; three or more months post-transplant; and presenting with signs, symptoms and laboratory findings suggestive of allograft rejection. Each assessment round will consist of 3 simulated patients. In between assessment rounds, physicians randomized into the intervention arm will receive educational materials on the new allograft rejection test.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnosis-Treatment</measure>
    <time_frame>3 months</time_frame>
    <description>Difference-in-differences regression analysis between the control and the intervention group's identification and treatment of hyperglycemia, as measured by the participants diagnostic and treatment CPV case domain scores. In each domain of a CPV (history, physical exam, workup, diagnosis and treatment), participants' care recommendations are evaluated against evidence-based care scoring criteria which can sum to a high potential score of up to 100% in each domain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Care: CPV scores</measure>
    <time_frame>3 months</time_frame>
    <description>Difference-in-differences regression analysis between the control and the intervention group's overall quality of care scores. In each CPV case, participants' care recommendations are evaluated against evidence-based care scoring criteria which can sum to a high potential score of up to 100% in each case.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Workup Costs</measure>
    <time_frame>3 months</time_frame>
    <description>Difference-in-differences regression analysis between between the control and the intervention group in the average cost of diagnostic tests ordered.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">175</enrollment>
  <condition>Transplant;Failure,Kidney</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Control participants will care for the same set of CPV patients as the intervention arm, but will not have knowledge of or access to Natera's dd-cfDNA test results. Investigators will compare control participants' clinical recommendations to those in the intervention arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention participants will care for the same set of CPV patients as the control arm, but will be educated on and given access to Natera's dd-cfDNA test results. Investigators will compare intervention participants' clinical recommendations to those in the control arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Natera KidneyScan</intervention_name>
    <description>Online educational materials on Natera Kidneyscan (dd-cfDNA) and sample test results for simulated patients</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical Performance and Value Vignettes</intervention_name>
    <description>Online renal allograft simulated patients</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>CPVs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A minimum of 2 years post-residency but no more than 40 years in practice&#xD;
&#xD;
          -  Board-certified in internal medicine&#xD;
&#xD;
          -  Completion of a nephrology fellowship&#xD;
&#xD;
          -  In a private solo or multi-group practice&#xD;
&#xD;
          -  Minimum threshold of 5 post-kidney transplant (KT) patients currently seen monthly&#xD;
&#xD;
          -  Informed, signed and voluntarily consented to be in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not board certified in internal medicine&#xD;
&#xD;
          -  Have practiced as a board-certified physician for less than 2 or greater than 40 years&#xD;
&#xD;
          -  See &lt;5 post-transplant patients monthly&#xD;
&#xD;
          -  Non-English speaking&#xD;
&#xD;
          -  Unable to access the internet&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John W Peabody, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>President</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>QURE Healthcare</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>September 14, 2020</last_update_submitted>
  <last_update_submitted_qc>September 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Qure Healthcare, LLC</investigator_affiliation>
    <investigator_full_name>David Paculdo</investigator_full_name>
    <investigator_title>John W Peabody, MD PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</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/NCT03765203
org study id: Pro00030299
nct id: NCT03765203
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Detecting allograft injury and rejection is critical to preventing graft loss. The current
      standard of care (SoC) relies on serum creatinine (SC) and biopsy to monitor for and identify
      kidney injury earlier. SC has poor specificity and sensitivity and response to rejection is
      often delayed. Protocol biopsy is more accurate but involves the risk of complications. A
      more definitive, less invasive method for monitoring injury and early rejection is needed.

      We report on the clinical utility of donor-derived cell-free DNA (dd-cfDNA) in transplant
      recipients' blood, measured using a novel SNP-based mmPCR NGS methodology, to diagnose
      allograft injury/rejection. In this study, investigators will measure how use of dd-cfDNA
      changes clinical practice.
Five-year kidney allograft survival rates are estimated to be as low as 71.6%. A leading
      cause for the high prevalence of graft loss is the delay in detecting allograft injury from
      active rejection, when early diagnosis and intervention presents the greatest chance of
      preserving kidney function. Despite the frequent testing called for by care protocols, low
      levels of injury can go undetected due to the low specificity and sensitivity of current,
      standard testing methods: checking creatinine and immunosuppressive drug levels. More
      definitive graft biopsies are an option, but they are invasive, expensive and can even put
      the patient at risk for graft loss and other complications, making it undesirable as a
      frequent monitoring test.

      Donor-derived cell-free DNA (dd-cfDNA) detected in the blood of transplant recipients has
      been shown to be a non-invasive diagnostic marker for allograft injury/rejection. Natera,
      Inc. has recently developed a novel single nucleotide polymorphism (SNP)-based mmPCR NGS
      methodology to measure dd-cfDNA in kidney transplant recipients for the detection of
      allograft injury and rejection. As a growing leader in the diagnostic space, Natera has
      commissioned a randomized controlled trial to determine the clinical utility of its dd-cfDNA
      detection methodology for practicing nephrologists treating kidney allograft patients. This
      study is expected to fill a gap in the evidence base on the clinical utility of dd-cfDNA
      testing for allograft rejection.

      The study is a pre-post, two round controlled trial of care practices in a nationally
      representative sample of practicing nephrologists randomly assigned to a control or an
      intervention arm. All participants will be asked to propose care for a total of 6 CPV
      simulated patients who are adults aged 30-75; three or more months post-transplant; and
      presenting with signs, symptoms and laboratory findings suggestive of allograft rejection.
      Each assessment round will consist of 3 simulated patients. In between assessment rounds,
      participants randomized into the intervention arm will receive educational materials on the
      new allograft rejection test.

      Investigators will assess whether practicing nephrologists more effectively identify and
      manage patients with possible kidney allograft rejection when given access to Natera's novel
      SNP-based mmPCR-NGS test that measures dd-cfDNA, and, whether those behavioral changes
      improves patient management and optimizes resource utilization.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study is a pre-post, two round controlled trial of care practices in a nationally representative sample of practicing nephrologists randomly assigned to a control or an intervention arm. All providers will be asked to propose care for a total of 6 CPV simulated patients who are adults aged 30-75; three or more months post-transplant; and presenting with signs, symptoms and laboratory findings suggestive of allograft rejection. Each assessment round will consist of 3 simulated patients. In between assessment rounds, physicians randomized into the intervention arm will receive educational materials on the new allograft rejection test.
primary purpose: Other
masking: None (Open Label)
measure: Diagnosis-Treatment
time frame: 3 months
description: Difference-in-differences regression analysis between the control and the intervention group's identification and treatment of hyperglycemia, as measured by the participants diagnostic and treatment CPV case domain scores. In each domain of a CPV (history, physical exam, workup, diagnosis and treatment), participants' care recommendations are evaluated against evidence-based care scoring criteria which can sum to a high potential score of up to 100% in each domain.
measure: Quality of Care: CPV scores
time frame: 3 months
description: Difference-in-differences regression analysis between the control and the intervention group's overall quality of care scores. In each CPV case, participants' care recommendations are evaluated against evidence-based care scoring criteria which can sum to a high potential score of up to 100% in each case.
measure: Workup Costs
time frame: 3 months
description: Difference-in-differences regression analysis between between the control and the intervention group in the average cost of diagnostic tests ordered.
arm group label: Control
arm group type: Active Comparator
description: Control participants will care for the same set of CPV patients as the intervention arm, but will not have knowledge of or access to Natera's dd-cfDNA test results. Investigators will compare control participants' clinical recommendations to those in the intervention arm.
arm group label: Intervention
arm group type: Experimental
description: Intervention participants will care for the same set of CPV patients as the control arm, but will be educated on and given access to Natera's dd-cfDNA test results. Investigators will compare intervention participants' clinical recommendations to those in the control arm.
intervention type: Diagnostic Test
intervention name: Natera KidneyScan
description: Online educational materials on Natera Kidneyscan (dd-cfDNA) and sample test results for simulated patients
arm group label: Intervention
intervention type: Other
intervention name: Clinical Performance and Value Vignettes
description: Online renal allograft simulated patients
arm group label: Control
arm group label: Intervention
other name: CPVs
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: John W Peabody, MD PhD
role: Principal Investigator
affiliation: President
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Qure Healthcare, LLC
investigator full name: David Paculdo
investigator title: John W Peabody, MD PhD
mesh term: Renal Insufficiency
sharing ipd: No