<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/NCT03290469</url>
  </required_header>
  <id_info>
    <org_study_id>NICU-R001</org_study_id>
    <nct_id>NCT03290469</nct_id>
  </id_info>
  <brief_title>NICUSeq: A Trial to Evaluate the Clinical Utility of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Acute Care Neonates and Infants</brief_title>
  <acronym>NICU-Seq</acronym>
  <official_title>NICUSeq: A Prospective Trial to Evaluate the Clinical Utility of Human Whole Genome Sequencing (WGS) Compared to Standard of Care in Acute Care Neonates and Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Illumina, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Le Bonheur Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rady Pediatric Genomics &amp; Systems Medicine Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital of Orange County</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital and Medical Center, Omaha, Nebraska</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Louis Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Illumina, Inc.</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>
      Prospective, multi-site, study to evaluate the clinical utility of cWGS in a proband. One&#xD;
      group will receive cWGS and a clinical report approximately 15 days after blood samples are&#xD;
      received, while the other group will continue to receive standard of care until Day 60. The&#xD;
      standard of care group will receive cWGS and a clinical report at Day 60 as part of secondary&#xD;
      and tertiary analyses. Both groups will be followed for a total of 90 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, multi-site, randomized study to evaluate the clinical utility of cWGS&#xD;
      in each proband. Throughout this study, each proband will receive SOC testing as determined&#xD;
      by the site clinical team. Upon enrollment in the study, each proband will be randomly&#xD;
      assigned to the 15 day cWGS group or the SOC group. SOC is defined as the management of the&#xD;
      proband's care under the same or similar conditions as if the proband was not enrolled in&#xD;
      this study. A blood sample from each enrolled proband will be collected and shipped to the&#xD;
      Illumina Clinical Services Laboratory (&quot;ICSL&quot;), which is Clinical Laboratory Improvement&#xD;
      Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited. ICSL will&#xD;
      conduct cWGS testing with the TruGenome Undiagnosed Disease Test (&quot;TruGenome Test&quot;). The&#xD;
      TruGenome Test cWGS results will be provided to the Principal Investigator (PI) or designee&#xD;
      who will evaluate each proband test outcome based on the aggregate medical information,&#xD;
      informed by the cWGS or SOC results.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 14, 2017</start_date>
  <completion_date type="Actual">January 13, 2020</completion_date>
  <primary_completion_date type="Actual">April 30, 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>Multi-cohort, time delay study receiving Clinical Whole Genome Sequencing (cWGS) at either 15 days or 60 days in an acutely ill newborn population</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>All investigators are masked to the study arm until Day 15 to ensure SOC throughout first 15 days on study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>A difference in Change of Management between the 15 day cWGS and standard of care groups</measure>
    <time_frame>Day 60</time_frame>
    <description>Change of Management is a binary (yes or no) based on assignments made by the PI or designee at each site using the following domains:&#xD;
Condition specific management&#xD;
Condition specific supportive interventions&#xD;
Palliative care/End of Life Care A change in any of these domains will be considered a change of management.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic Yield</measure>
    <time_frame>90 Days</time_frame>
    <description>Diagnostic yield (# positive diagnoses/ total # of each proband expressed as a percentage)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic Accuracy</measure>
    <time_frame>90 Days</time_frame>
    <description>Diagnostic accuracy (percent positive agreement between test outcome classified by the medical monitor and the site PI or designee)&#xD;
% diagnoses returned before discharge or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic Results Returned</measure>
    <time_frame>90 Days</time_frame>
    <description>% diagnoses returned before discharge or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Costs</measure>
    <time_frame>90 Days</time_frame>
    <description>Pre-test costs of hospital care</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Time to Diagnosis</measure>
    <time_frame>90 Days</time_frame>
    <description>Average time (in days) to diagnose between cWGS and SOC based on the comparison of the (a) cWGS results and the (b) current clinical diagnoses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The amount of imaging tests ordered as assessed by counting the number of tests per cohort.</measure>
    <time_frame>90 Days</time_frame>
    <description>Clinical services utilization includes the number of imaging tests ordered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study.</measure>
    <time_frame>90 Days</time_frame>
    <description>The questionnaire is a likard scale questionnaire developed by the study team to assess satisfaction levels from the perspective of the clinician and also the parent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Clinical Utility by using a questionnaire</measure>
    <time_frame>90 Days</time_frame>
    <description>A questionnaire developed by the study team will assess the Clinical Utility of the cWGS test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Care Setting from the ICU environment</measure>
    <time_frame>90 Days</time_frame>
    <description>Changes in care level setting from the ICU environment will be compared between the 15 day cWGS group and the SOC group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to diagnosis</measure>
    <time_frame>90 Days</time_frame>
    <description>Time to diagnosis (in days of life)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">355</enrollment>
  <condition>Rare Diseases</condition>
  <arm_group>
    <arm_group_label>15 day cWGS and Standard of Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enrolled cohorts receive the results of the clinical whole genome sequencing (cWGS) after 15 days of the sample receipt while still undergoing standard of care (SOC).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Enrolled cohorts receive the results of the clinical whole genome sequencing (cWGS) after 60 days of the sample receipt while still undergoing standard of care (SOC).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>clinical whole genome sequencing (cWGS)</intervention_name>
    <description>Clinical Whole Genome Sequencing (cWGS) consists of the sequencing, analysis and interpretation of subjects samples and a return of the result to the ordering physician.</description>
    <arm_group_label>15 day cWGS and Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Proband Inclusion Criteria&#xD;
&#xD;
          1. Current admission in a Neonatal Intensive Care Unit/Intensive Care Unit at a&#xD;
             participating clinical site at the time of enrollment from day of life 0 to 120 days&#xD;
&#xD;
          2. A suspected genetic etiology of disease, based on objective clinical findings or other&#xD;
             phenotypic defects for which a genetic test would be considered&#xD;
&#xD;
          3. Must be able to have 1 - 1.25 ml tube of whole blood drawn for testing&#xD;
&#xD;
          4. One parent of the proband must be able to provide written informed consent&#xD;
&#xD;
          5. At least one biological parent must agree to participate and provide at least 4 ml of&#xD;
             whole blood for testing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Proband Exclusion Criteria&#xD;
&#xD;
          1. Known non-genetic cause(s) of disease, disorder, or phenotypic defect&#xD;
&#xD;
          2. The phenotype is fully explained by complications of prematurity&#xD;
&#xD;
          3. Trisomy 13, 18 or 21 or Turner Syndrome is the likely diagnosis; such a proband will&#xD;
             be eligible if a diagnostic karyotype is normal&#xD;
&#xD;
          4. Blood transfusion within 48 hours (each proband will be re-eligible 48 hours after the&#xD;
             most recent transfusion)&#xD;
&#xD;
          5. The PI decides that the study is not in the best interest of the proband (for example,&#xD;
             the neonate or infant is at a high risk of severe morbidity or mortality within the&#xD;
             next 7 days and these risks could be mitigated by alternative testing). Subsequent&#xD;
             eligibility for enrollment of each proband is at the discretion of the site PI.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>120 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ryan J. Taft, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Illumina, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rady's/Children's Hospital of Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis School of Medicine &amp; St. Louis Children's Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center &amp; Children's Hospital</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelpia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LeBonheur Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>November 16, 2020</last_update_submitted>
  <last_update_submitted_qc>November 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ICU</keyword>
  <keyword>Intensive Care Unit</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rare Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Deidentified and curated variant and limited phenotype information will be submitted to ClinVar. ClinVar is a freely accessible, public archive of reports of the relationships among human variations and phenotypes hosted by the National Center for Biotechnology Information (NCBI) and funded by Intramural National Institutes of Health (NIH) funding. No personal health information (PHI) or information identifying the participant or family will be submitted.</ipd_description>
  </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/NCT03290469
org study id: NICU-R001
nct id: NCT03290469
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prospective, multi-site, study to evaluate the clinical utility of cWGS in a proband. One
      group will receive cWGS and a clinical report approximately 15 days after blood samples are
      received, while the other group will continue to receive standard of care until Day 60. The
      standard of care group will receive cWGS and a clinical report at Day 60 as part of secondary
      and tertiary analyses. Both groups will be followed for a total of 90 days.
This is a prospective, multi-site, randomized study to evaluate the clinical utility of cWGS
      in each proband. Throughout this study, each proband will receive SOC testing as determined
      by the site clinical team. Upon enrollment in the study, each proband will be randomly
      assigned to the 15 day cWGS group or the SOC group. SOC is defined as the management of the
      proband's care under the same or similar conditions as if the proband was not enrolled in
      this study. A blood sample from each enrolled proband will be collected and shipped to the
      Illumina Clinical Services Laboratory ("ICSL"), which is Clinical Laboratory Improvement
      Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited. ICSL will
      conduct cWGS testing with the TruGenome Undiagnosed Disease Test ("TruGenome Test"). The
      TruGenome Test cWGS results will be provided to the Principal Investigator (PI) or designee
      who will evaluate each proband test outcome based on the aggregate medical information,
      informed by the cWGS or SOC results.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multi-cohort, time delay study receiving Clinical Whole Genome Sequencing (cWGS) at either 15 days or 60 days in an acutely ill newborn population
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
masking description: All investigators are masked to the study arm until Day 15 to ensure SOC throughout first 15 days on study.
measure: A difference in Change of Management between the 15 day cWGS and standard of care groups
time frame: Day 60
description: Change of Management is a binary (yes or no) based on assignments made by the PI or designee at each site using the following domains:
Condition specific management
Condition specific supportive interventions
Palliative care/End of Life Care A change in any of these domains will be considered a change of management.
measure: Diagnostic Yield
time frame: 90 Days
description: Diagnostic yield (# positive diagnoses/ total # of each proband expressed as a percentage)
measure: Diagnostic Accuracy
time frame: 90 Days
description: Diagnostic accuracy (percent positive agreement between test outcome classified by the medical monitor and the site PI or designee)
% diagnoses returned before discharge or death
measure: Genetic Results Returned
time frame: 90 Days
description: % diagnoses returned before discharge or death
measure: Costs
time frame: 90 Days
description: Pre-test costs of hospital care
measure: Average Time to Diagnosis
time frame: 90 Days
description: Average time (in days) to diagnose between cWGS and SOC based on the comparison of the (a) cWGS results and the (b) current clinical diagnoses
measure: The amount of imaging tests ordered as assessed by counting the number of tests per cohort.
time frame: 90 Days
description: Clinical services utilization includes the number of imaging tests ordered.
measure: cWGS satisfaction questionnaire will be given to clinicians and families at the conclusion of the study.
time frame: 90 Days
description: The questionnaire is a likard scale questionnaire developed by the study team to assess satisfaction levels from the perspective of the clinician and also the parent.
measure: Assessment of Clinical Utility by using a questionnaire
time frame: 90 Days
description: A questionnaire developed by the study team will assess the Clinical Utility of the cWGS test
measure: Change in Care Setting from the ICU environment
time frame: 90 Days
description: Changes in care level setting from the ICU environment will be compared between the 15 day cWGS group and the SOC group.
measure: Time to diagnosis
time frame: 90 Days
description: Time to diagnosis (in days of life)
arm group label: 15 day cWGS and Standard of Care
arm group type: Experimental
description: Enrolled cohorts receive the results of the clinical whole genome sequencing (cWGS) after 15 days of the sample receipt while still undergoing standard of care (SOC).
arm group label: Standard of Care
arm group type: No Intervention
description: Enrolled cohorts receive the results of the clinical whole genome sequencing (cWGS) after 60 days of the sample receipt while still undergoing standard of care (SOC).
intervention type: Other
intervention name: clinical whole genome sequencing (cWGS)
description: Clinical Whole Genome Sequencing (cWGS) consists of the sequencing, analysis and interpretation of subjects samples and a return of the result to the ordering physician.
arm group label: 15 day cWGS and Standard of Care
criteria: 
gender: All
minimum age: 1 Day
maximum age: 120 Days
healthy volunteers: No
last name: Ryan J. Taft, PhD
role: Study Director
affiliation: Illumina, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rare Diseases
sharing ipd: No
ipd description: Deidentified and curated variant and limited phenotype information will be submitted to ClinVar. ClinVar is a freely accessible, public archive of reports of the relationships among human variations and phenotypes hosted by the National Center for Biotechnology Information (NCBI) and funded by Intramural National Institutes of Health (NIH) funding. No personal health information (PHI) or information identifying the participant or family will be submitted.