xml: <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/NCT05996094</url>
    </required_header>
    <id_info>
      <org_study_id>3578141P111242020012800013</org_study_id>
      <nct_id>NCT05996094</nct_id>
    </id_info>
    <brief_title>Antiretroviral Adherence and Drug-level Monitoring</brief_title>
    <official_title>Adherence and Pharmacokinetics Measures in People Living With HIV Receiving Tenofovir Disoproxil Fumarate-based Regimens in Indonesia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zamrotul Izzah</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Universitas Airlangga</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Groningen</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>
        This observational study aims to investigate medication adherence and drug-level monitoring&#xD;
        of antiretroviral agents in a cohort of people living with HIV in Indonesia. The study is&#xD;
        conducted in outpatients receiving tenofovir-based regimens in a university medical centre.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Optimal adherence is critical to achieve and sustain viral suppression. Currently, there is&#xD;
        no gold standard measure of antiretroviral adherence and exposure in clinical practice.&#xD;
        Recent studies have evaluated the use of emerging biological matrices such as dried blood&#xD;
        spots, urine, and saliva as means of objective adherence measures. For drug-level monitoring,&#xD;
        tenofovir is selected as a drug of interest and thus only people receiving tenofovir&#xD;
        disoproxil fumarate-based regimens will be monitored. Some studies have reported that higher&#xD;
        plasma trough concentrations of tenofovir were associated with renal toxicity. Therefore,&#xD;
        this project aims to measure level of adherence and tenofovir concentrations in plasma and&#xD;
        emerging matrices among people living with HIV in Indonesia. Primary outcome is adherence to&#xD;
        ART that will be measured using multi methods, including self-report questionnaire, pill&#xD;
        counting, electronic monitoring, and drug-level testing. Secondary outcomes include tenofovir&#xD;
        concentrations in plasma, urine, saliva, and dried blood spots and clinical outcomes (viral&#xD;
        load and CD4 count). Assays for measuring tenofovir concentrations will be developed using&#xD;
        high-performance liquid chromatography-tandem mass spectrometry. Concentrations derived from&#xD;
        dried blood spots, saliva, and urine will be compared to plasma concentrations.&#xD;
        Pharmacokinetic models will be used to interpret drug-level monitoring. The association of&#xD;
        adherence measures as well as drug concentrations and clinical outcomes will be examined.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">October 16, 2020</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</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>Adherence to antiretroviral therapy</measure>
      <time_frame>Baseline and 6 months</time_frame>
      <description>Adherence to antiretroviral therapy (ART) will be assessed using a validated Bahasa Indonesia version of self-reported adherence questionnaire. The questionnaire will recall ART use in the past week, past month, and past three months. The percentages of adherence will be calculated by the formula: (total number of dosage units prescribed - total number of times reported) / (total number of dosage units prescribed) × 100. The adherence scales range from 0 to 100% with higher scales denote higher adherence. Being highly adherent to ART is defined by having an adherence higher than 80%.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Tenofovir concentrations</measure>
      <time_frame>Baseline (pre-dose, 1, and 4 h post-dose) and 6 months (random 3 - 16 h post-dose)</time_frame>
      <description>Concentrations of tenofovir in plasma, saliva, urine, and dried blood spots</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Viral load</measure>
      <time_frame>Baseline and 6 months</time_frame>
      <description>The viral load test will measure the number of HIV copies in plasma (in copies/ml).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CD4 cell count</measure>
      <time_frame>Baseline and 6 months</time_frame>
      <description>The cluster of differentiation 4 (CD4) cell count test will quantify CD4 cells in plasma (in cells/mm^3).</description>
    </secondary_outcome>
    <enrollment type="Anticipated">100</enrollment>
    <condition>HIV Infections</condition>
    <condition>AIDS</condition>
    <condition>Antiretroviral Therapy, Highly Active</condition>
    <condition>Adherence, Medication</condition>
    <condition>Drug-level Monitoring</condition>
    <eligibility>
      <study_pop>
        <textblock>
          All people living with HIV receiving antiretroviral therapy who regularly visit the HIV&#xD;
          clinic at a university medical centre in Surabaya, Indonesia, during study period.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults with HIV who have been receiving antiretroviral therapy containing&#xD;
               tenofovir-based regimens for at least six months&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant and breastfeeding women, people with kidney failure, undergoing hemodialysis&#xD;
               or peritoneal dialysis, uncontrolled diabetes, uncontrolled hypertension, and&#xD;
               hypersensitivity to tenofovir&#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>Zamrotul Izzah</last_name>
      <role>Principal Investigator</role>
      <affiliation>Universitas Airlangga</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zamrotul Izzah</last_name>
      <phone>6285655191257</phone>
      <email>zamrotulizzah@ff.unair.ac.id</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Tri Pudy Asmarawati</last_name>
      <email>tpasmarawati@fk.unair.ac.id</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Universitas Airlangga Hospital</name>
        <address>
          <city>Surabaya</city>
          <state>East Java</state>
          <zip>60115</zip>
          <country>Indonesia</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tri Pudy Asmarawati, MD</last_name>
        <email>tpasmarawati@fk.unair.ac.id</email>
      </contact>
      <contact_backup>
        <last_name>Dwi Suyanti</last_name>
      </contact_backup>
    </location>
    <location_countries>
      <country>Indonesia</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Groningen</investigator_affiliation>
      <investigator_full_name>Zamrotul Izzah</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Adherence</keyword>
    <keyword>Adult</keyword>
    <keyword>Pharmacokinetics</keyword>
    <keyword>Tenofovir</keyword>
    <keyword>Viral Load</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>HIV Infections</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>De-identified data will be available for analysing and reporting purposes and for other parties upon formal request to the principal investigators.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05996094
  org study id: 3578141P111242020012800013
  nct id: NCT05996094
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This observational study aims to investigate medication adherence and drug-level monitoring
        of antiretroviral agents in a cohort of people living with HIV in Indonesia. The study is
        conducted in outpatients receiving tenofovir-based regimens in a university medical centre.
  Optimal adherence is critical to achieve and sustain viral suppression. Currently, there is
        no gold standard measure of antiretroviral adherence and exposure in clinical practice.
        Recent studies have evaluated the use of emerging biological matrices such as dried blood
        spots, urine, and saliva as means of objective adherence measures. For drug-level monitoring,
        tenofovir is selected as a drug of interest and thus only people receiving tenofovir
        disoproxil fumarate-based regimens will be monitored. Some studies have reported that higher
        plasma trough concentrations of tenofovir were associated with renal toxicity. Therefore,
        this project aims to measure level of adherence and tenofovir concentrations in plasma and
        emerging matrices among people living with HIV in Indonesia. Primary outcome is adherence to
        ART that will be measured using multi methods, including self-report questionnaire, pill
        counting, electronic monitoring, and drug-level testing. Secondary outcomes include tenofovir
        concentrations in plasma, urine, saliva, and dried blood spots and clinical outcomes (viral
        load and CD4 count). Assays for measuring tenofovir concentrations will be developed using
        high-performance liquid chromatography-tandem mass spectrometry. Concentrations derived from
        dried blood spots, saliva, and urine will be compared to plasma concentrations.
        Pharmacokinetic models will be used to interpret drug-level monitoring. The association of
        adherence measures as well as drug concentrations and clinical outcomes will be examined.
  observational model: Cohort
  time perspective: Prospective
  measure: Adherence to antiretroviral therapy
  time frame: Baseline and 6 months
  description: Adherence to antiretroviral therapy (ART) will be assessed using a validated Bahasa Indonesia version of self-reported adherence questionnaire. The questionnaire will recall ART use in the past week, past month, and past three months. The percentages of adherence will be calculated by the formula: (total number of dosage units prescribed - total number of times reported) / (total number of dosage units prescribed) × 100. The adherence scales range from 0 to 100% with higher scales denote higher adherence. Being highly adherent to ART is defined by having an adherence higher than 80%.
  measure: Tenofovir concentrations
  time frame: Baseline (pre-dose, 1, and 4 h post-dose) and 6 months (random 3 - 16 h post-dose)
  description: Concentrations of tenofovir in plasma, saliva, urine, and dried blood spots
  measure: Viral load
  time frame: Baseline and 6 months
  description: The viral load test will measure the number of HIV copies in plasma (in copies/ml).
  measure: CD4 cell count
  time frame: Baseline and 6 months
  description: The cluster of differentiation 4 (CD4) cell count test will quantify CD4 cells in plasma (in cells/mm^3).
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Zamrotul Izzah
  role: Principal Investigator
  affiliation: Universitas Airlangga
  last name: Zamrotul Izzah
  phone: 6285655191257
  email: zamrotulizzah@ff.unair.ac.id
  last name: Tri Pudy Asmarawati
  email: tpasmarawati@fk.unair.ac.id
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: Indonesia
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Groningen
  investigator full name: Zamrotul Izzah
  investigator title: Principal Investigator
  mesh term: HIV Infections
  sharing ipd: No
  ipd description: De-identified data will be available for analysing and reporting purposes and for other parties upon formal request to the principal investigators.