<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/NCT02197845</url>
  </required_header>
  <id_info>
    <org_study_id>HM14641</org_study_id>
    <secondary_id>1R18HL112737-01</secondary_id>
    <nct_id>NCT02197845</nct_id>
  </id_info>
  <brief_title>Enhancing Use of Hydroxyurea In Sickle Cell Disease Using Patient Navigators</brief_title>
  <acronym>SHiP HU</acronym>
  <official_title>Enhancing Use of Hydroxyurea In Sickle Cell Disease Using Patient Navigators</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eastern Virginia Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital of The King's Daughters</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Virginia Department of Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>James Madison University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Multi-phase, patient navigator-based program in the Richmond and Tidewater regions of&#xD;
      Virginia to demonstrate:&#xD;
&#xD;
        1. the feasibility of using patient navigators to improve the percentage of children and&#xD;
           adult (age 15 and older) patients with sickle cell disease (SCD) in SCD specialty care&#xD;
&#xD;
        2. the efficacy of using patient navigators to improve hydroxyurea (HU) (re-)initiation and&#xD;
           adherence among adult patients with SCD eligible for HU&#xD;
&#xD;
      (Patient navigators may also be known as public health workers.)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The state of Virginia, including the Virginia Department of Health and three academic medical&#xD;
      centers and one federally qualified health center, plans a two-phase demonstration, first of&#xD;
      improvement in the percentage of adults with SCD who are in SCD specialty care (Phase I),&#xD;
      then of improvement in adherence to HU of eligible SCD adults (Phase II). Both phases will&#xD;
      use existing academic SCD providers, and an innovative, multimodal strategy, featuring&#xD;
      specially trained SCD patient navigators (PNs), that addresses barriers to care and to HU&#xD;
      use. In Phase I we will demonstrate the feasibility of utilizing PNs to overcome patient&#xD;
      access barriers to SCD care. In Phase II we will test the efficacy of PNs for overcoming&#xD;
      barriers to acceptance of and adherence with HU therapy. Patients will be randomized to a PN&#xD;
      arm or to a usual care arm. Providers will implement NIH guidelines for HU eligibility and&#xD;
      prescribing in both arms. All HU eligible patients will be offered HU at each clinical visit.&#xD;
      Among patients prescribed HU, if a maximum tolerated dose (MTD, defined in end points) has&#xD;
      not been reached, providers will dose escalate every 8-12 weeks to MTD, rather than to&#xD;
      clinical effect, before declaring treatment success or failure.&#xD;
&#xD;
      This project will be critically important and impactful by demonstrating the feasibility of a&#xD;
      statewide community-based strategy to assist vulnerable SCD adults in obtaining SCD specialty&#xD;
      care and likely prolonging life, a model that other states could adopt.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">July 7, 2018</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>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I: Percent of enrolled Phase I subjects who complete a provider visit by 3 months post enrollment</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II: Increase in fetal hemoglobin (HbF) as measured by hemoglobin electrophoresis</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase II: Measures of adherence to HU</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>For patients prescribed HU, clinical research coordinators will assess HU prescription refills from pill counts, pharmacy records, and self-report at baseline, 6 months, and 1 year. Patient navigators will regularly assess their patients' HU adherence by conducting pill counts at home visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Percent of patients achieving either maximum tolerated dose (MTD) or maximum dose</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Maximum tolerated dose (MTD) is the daily single oral dose that can be maintained for at least 16 weeks without toxicity (&lt; 3 x l09 neutrophils/L, &lt;100 x l09 platelets/L, &lt; 125 x l09 reticulocytes/L, 20% drop in [Hb] or an absolute value of &lt;4.5 g/dL, 50% rise in creatinine or absolute increase of &gt;0.4 mg/dL, 100% rise in ALT,GI disturbance, or rash or hair loss not attributable to other causes). Maximum dose is 35 mg/kg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Number of emergency department and hospital visits</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Mean corpuscular volume</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Total hemoglobin</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: White blood cell count</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Reticulocyte count</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Quality of life measures</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me), Patient Reported Outcomes Measurement Information System (PROMIS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Patient activation measures</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Patient Activation Measure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Patient knowledge measures</measure>
    <time_frame>1 year</time_frame>
    <description>Assessment of Sickle Cell Knowledge - University of Florida (UF-ASCK) (unpublished)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Health care knowledge and skills, self-efficacy, sickle cell stress measures</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Sickle Cell Transition intervention Program (TIP) Survey (non-validated)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Social support measures</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Sickle Cell Transition intervention Program (TIP) Survey (non-validated) and Multidimensional Scale of Perceived Social Support</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Coping strategies</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Coping Strategies Questionnaire for SCD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Associated pain conditions and comorbidities</measure>
    <time_frame>Baseline, 6 months, 1 year</time_frame>
    <description>Chart Review, Self Report and Surveys: Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me), Patient Reported Outcomes Measurement Information System (PROMIS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Blood transfusion measures (if applicable)</measure>
    <time_frame>6 months, 1 year</time_frame>
    <description>Chart review</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Patient Navigator Satisfaction (if applicable)</measure>
    <time_frame>1 year</time_frame>
    <description>Patient Navigator Satisfaction Surveys, 12 month follow up, Patient Study Experience Review for Patient Navigators</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">353</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>Phase I: Recruitment into Specialty Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the Phase I Experimental Arm are enrolled into SCD specialty care. PN's will contact patient up to 3 times to assure patients have had an initial visit by 3 months time.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase II: Patient Navigator Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the Phase II Experimental Arm follow routine clinical care and are assigned a Patient Navigator. A specially trained (SCD specefic)PN will work with participants for one year. Participants will be contacted by their Navigator weekly for the first 6 months, then biweekly for the second 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase II: Passenger Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No Intervention. Participants in the Phase II Passenger Arm follow routine clinical care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Patient Navigator</intervention_name>
    <description>A specially trained (SCD knowledgable) Patient Navigator will act as a liaison who assists participants in increasing adherence to HU through disease education, addressing barriers to care and improving adherence to HU. PN utilize various techniques geared toward the individual patients needs. Interventions utilized by a PN include improving disease management skills, educational materials about disease, HU adherence, motivational interviewing, care coordination and social support.</description>
    <arm_group_label>Phase II: Patient Navigator Arm</arm_group_label>
    <other_name>Public Health Worker</other_name>
    <other_name>Community Health Worker</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Recruitment into Specialty Care</intervention_name>
    <description>A specially trained (SCD knowledgeable) Patient Navigator will act as a liaison to participants in increasing adherence to Hydroxyurea. Interventions utilized by a PN include teaching disease management skills, addressing barriers to care, disease education, HU management, motivational interviewing, care coordination and social support.</description>
    <arm_group_label>Phase I: Recruitment into Specialty Care</arm_group_label>
    <other_name>Sickle Cell Disease Specialty Care</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        PHASE I:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient Self Report of Sickle Cell Disease (Genotypes: Hb SS, SC, SBoThal, SB+Thal)&#xD;
&#xD;
          -  15 years or older&#xD;
&#xD;
          -  Virginia resident&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -Visited one of a pre-selected list of sickle cell specialists in Virginia within the last&#xD;
        6 months&#xD;
&#xD;
        PHASE II:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Sickle Cell Disease (SCD) patient (Genotypes: SS or SBoThal)&#xD;
&#xD;
          -  Eligible for Hydroxyurea (according to NIH guidelines)&#xD;
&#xD;
          -  15 years or older&#xD;
&#xD;
          -  Virginia resident&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Enrollment in scheduled chronic transfusion program&#xD;
&#xD;
          -  SCD Genotype: Hb SC and SB+Thal)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wally R Smith, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>May 31, 2023</last_update_submitted>
  <last_update_submitted_qc>May 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sickle cell disease</keyword>
  <keyword>hydroxyurea</keyword>
  <keyword>patient navigator</keyword>
  <keyword>community health worker</keyword>
  <keyword>public health worker</keyword>
  <keyword>fetal hemoglobin</keyword>
  <keyword>health services research</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT02197845/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT02197845
org study id: HM14641
secondary id: 1R18HL112737-01
nct id: NCT02197845
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Multi-phase, patient navigator-based program in the Richmond and Tidewater regions of
      Virginia to demonstrate:

        1. the feasibility of using patient navigators to improve the percentage of children and
           adult (age 15 and older) patients with sickle cell disease (SCD) in SCD specialty care

        2. the efficacy of using patient navigators to improve hydroxyurea (HU) (re-)initiation and
           adherence among adult patients with SCD eligible for HU

      (Patient navigators may also be known as public health workers.)
The state of Virginia, including the Virginia Department of Health and three academic medical
      centers and one federally qualified health center, plans a two-phase demonstration, first of
      improvement in the percentage of adults with SCD who are in SCD specialty care (Phase I),
      then of improvement in adherence to HU of eligible SCD adults (Phase II). Both phases will
      use existing academic SCD providers, and an innovative, multimodal strategy, featuring
      specially trained SCD patient navigators (PNs), that addresses barriers to care and to HU
      use. In Phase I we will demonstrate the feasibility of utilizing PNs to overcome patient
      access barriers to SCD care. In Phase II we will test the efficacy of PNs for overcoming
      barriers to acceptance of and adherence with HU therapy. Patients will be randomized to a PN
      arm or to a usual care arm. Providers will implement NIH guidelines for HU eligibility and
      prescribing in both arms. All HU eligible patients will be offered HU at each clinical visit.
      Among patients prescribed HU, if a maximum tolerated dose (MTD, defined in end points) has
      not been reached, providers will dose escalate every 8-12 weeks to MTD, rather than to
      clinical effect, before declaring treatment success or failure.

      This project will be critically important and impactful by demonstrating the feasibility of a
      statewide community-based strategy to assist vulnerable SCD adults in obtaining SCD specialty
      care and likely prolonging life, a model that other states could adopt.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: Single (Investigator)
measure: Phase I: Percent of enrolled Phase I subjects who complete a provider visit by 3 months post enrollment
time frame: 3 months
measure: Phase II: Increase in fetal hemoglobin (HbF) as measured by hemoglobin electrophoresis
time frame: Baseline, 6 months, 1 year
measure: Phase II: Measures of adherence to HU
time frame: Baseline, 6 months, 1 year
description: For patients prescribed HU, clinical research coordinators will assess HU prescription refills from pill counts, pharmacy records, and self-report at baseline, 6 months, and 1 year. Patient navigators will regularly assess their patients' HU adherence by conducting pill counts at home visits.
measure: Phase II: Percent of patients achieving either maximum tolerated dose (MTD) or maximum dose
time frame: Baseline, 6 months, 1 year
description: Maximum tolerated dose (MTD) is the daily single oral dose that can be maintained for at least 16 weeks without toxicity (< 3 x l09 neutrophils/L, <100 x l09 platelets/L, < 125 x l09 reticulocytes/L, 20% drop in [Hb] or an absolute value of <4.5 g/dL, 50% rise in creatinine or absolute increase of >0.4 mg/dL, 100% rise in ALT,GI disturbance, or rash or hair loss not attributable to other causes). Maximum dose is 35 mg/kg.
measure: Phase II: Number of emergency department and hospital visits
time frame: Baseline, 6 months, 1 year
measure: Phase II: Mean corpuscular volume
time frame: Baseline, 6 months, 1 year
measure: Phase II: Total hemoglobin
time frame: Baseline, 6 months, 1 year
measure: Phase II: White blood cell count
time frame: Baseline, 6 months, 1 year
measure: Phase II: Reticulocyte count
time frame: Baseline, 6 months, 1 year
measure: Phase II: Quality of life measures
time frame: Baseline, 6 months, 1 year
description: Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me), Patient Reported Outcomes Measurement Information System (PROMIS)
measure: Phase II: Patient activation measures
time frame: Baseline, 6 months, 1 year
description: Patient Activation Measure
measure: Phase II: Patient knowledge measures
time frame: 1 year
description: Assessment of Sickle Cell Knowledge - University of Florida (UF-ASCK) (unpublished)
measure: Phase II: Health care knowledge and skills, self-efficacy, sickle cell stress measures
time frame: Baseline, 6 months, 1 year
description: Sickle Cell Transition intervention Program (TIP) Survey (non-validated)
measure: Phase II: Social support measures
time frame: Baseline, 6 months, 1 year
description: Sickle Cell Transition intervention Program (TIP) Survey (non-validated) and Multidimensional Scale of Perceived Social Support
measure: Phase II: Coping strategies
time frame: Baseline, 6 months, 1 year
description: Coping Strategies Questionnaire for SCD
measure: Phase II: Associated pain conditions and comorbidities
time frame: Baseline, 6 months, 1 year
description: Chart Review, Self Report and Surveys: Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me), Patient Reported Outcomes Measurement Information System (PROMIS)
measure: Phase II: Blood transfusion measures (if applicable)
time frame: 6 months, 1 year
description: Chart review
measure: Phase II: Patient Navigator Satisfaction (if applicable)
time frame: 1 year
description: Patient Navigator Satisfaction Surveys, 12 month follow up, Patient Study Experience Review for Patient Navigators
arm group label: Phase I: Recruitment into Specialty Care
arm group type: Experimental
description: Participants in the Phase I Experimental Arm are enrolled into SCD specialty care. PN's will contact patient up to 3 times to assure patients have had an initial visit by 3 months time.
arm group label: Phase II: Patient Navigator Arm
arm group type: Experimental
description: Participants in the Phase II Experimental Arm follow routine clinical care and are assigned a Patient Navigator. A specially trained (SCD specefic)PN will work with participants for one year. Participants will be contacted by their Navigator weekly for the first 6 months, then biweekly for the second 6 months.
arm group label: Phase II: Passenger Arm
arm group type: No Intervention
description: No Intervention. Participants in the Phase II Passenger Arm follow routine clinical care.
intervention type: Behavioral
intervention name: Patient Navigator
description: A specially trained (SCD knowledgable) Patient Navigator will act as a liaison who assists participants in increasing adherence to HU through disease education, addressing barriers to care and improving adherence to HU. PN utilize various techniques geared toward the individual patients needs. Interventions utilized by a PN include improving disease management skills, educational materials about disease, HU adherence, motivational interviewing, care coordination and social support.
arm group label: Phase II: Patient Navigator Arm
other name: Public Health Worker
other name: Community Health Worker
intervention type: Behavioral
intervention name: Recruitment into Specialty Care
description: A specially trained (SCD knowledgeable) Patient Navigator will act as a liaison to participants in increasing adherence to Hydroxyurea. Interventions utilized by a PN include teaching disease management skills, addressing barriers to care, disease education, HU management, motivational interviewing, care coordination and social support.
arm group label: Phase I: Recruitment into Specialty Care
other name: Sickle Cell Disease Specialty Care
criteria: 
gender: All
minimum age: 15 Years
maximum age: N/A
healthy volunteers: No
last name: Wally R Smith, MD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: No
provided document: 