<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/NCT02206555</url>
  </required_header>
  <id_info>
    <org_study_id>HEPP 1403</org_study_id>
    <secondary_id>14/098</secondary_id>
    <nct_id>NCT02206555</nct_id>
  </id_info>
  <brief_title>PrEP Demonstration Project (PRELUDE Study)</brief_title>
  <acronym>PRELUDE</acronym>
  <official_title>Implementation of HIV Preexposure Prophylaxis With Antiretroviral Medications Among People at High Risk for HIV Infection: A Demonstration Project</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kirby Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kirby Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Significant increases in HIV diagnoses among gay and other homosexually active men, in&#xD;
      Australia and internationally, have been observed since the late 1990s. The levels of high&#xD;
      HIV risk sexual practices among gay men have also increased, particularly unprotected anal&#xD;
      intercourse (UAI). Nationally, over three quarters of the new HIV infections diagnosed&#xD;
      annually are among men who have sex with men (MSM). The proportion of heterosexual men and&#xD;
      women among those diagnosed with HIV annually has also increased in recent years. Despite&#xD;
      successes in some situations, HIV transmission has not been adequately reduced by the&#xD;
      prevention methods available to those at risk, such as education, condoms, and treatment of&#xD;
      sexually transmitted infections (STIs).&#xD;
&#xD;
      The effectiveness of daily oral antiretroviral medications (ARVs) as preexposure prophylaxis&#xD;
      of HIV (PrEP) has now been established by clinical trials in both heterosexual adults and&#xD;
      homosexual men. Whether PrEP confers high rates of protection in real life situations and is&#xD;
      a feasible strategy to implement still requires further investigation. Through its &quot;HIV&#xD;
      prevention strategy 2015: New era,&quot; NSW Health committed to consider how to most&#xD;
      appropriately and efficiently implement PrEP in line with evidence. This commitment&#xD;
      translated in the support to this PrEP demonstration project.&#xD;
&#xD;
      This demonstration project is designed to evaluate the off-label provision of daily&#xD;
      combination of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC, known as TRUVADA) as&#xD;
      PrEP to a sample of sero-negative individuals at high risk for HIV infection in clinical&#xD;
      settings in New South Wales. The project will inform policy development regarding primary HIV&#xD;
      prevention with PrEP.&#xD;
&#xD;
      This is an open-label, single-arm treatment evaluation study. All consenting and eligible HIV&#xD;
      negative participants will receive TRUVADA prescribed for daily administration orally. At&#xD;
      each followup visit, the following procedures will be conducted: clinical evaluations/&#xD;
      procedures, laboratory evaluations/ procedures, testing for HIV, STIs, hepatic and renal&#xD;
      function, assessment for adherence to the prescribed medication, side effects, eligibility&#xD;
      for next TRUVADA prescription, and willingness to continue on PrEP.&#xD;
&#xD;
      As a study requirement, participants will be offered a self-administered assessment of&#xD;
      behaviour, lifestyle and attitudes which will be conducted ideally within two and no more&#xD;
      than seven days of the clinic visit in the participant's private space.&#xD;
&#xD;
      Analyses will include: the feasibility of PrEP delivery, adherence to the study medication,&#xD;
      safety and tolerability, the effects of PrEP use on behavior, and statistical analyses of the&#xD;
      risk of HIV seroconversion.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 14, 2014</start_date>
  <completion_date type="Actual">December 20, 2017</completion_date>
  <primary_completion_date type="Actual">November 28, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to accrual</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>Time to accrual of 300 person-years of follow-up on TRUVADA. Each participant will receive TRUVADA for a maximum of 12 months, and will be followed for an additional three months after discontinuation. (Primary endpoint: feasibility of the process of PrEP delivery in health care settings in NSW)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Seroconversion-free time on PrEP</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>Seroconversion-free time on PrEP (Primary endpoint: feasibility of the process of PrEP delivery in health care settings in NSW)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to TRUVADA discontinuation</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>Time to TRUVADA discontinuation (primary endpoint: adherence)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prescribed doses taken</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>Percentage of prescribed doses taken orally in the prescribed period (primary endpoint: adherence)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidents of HIV seroconversion</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Incidence of HIV seroconversion among study participants during the course of their study participation and in six months following PrEP discontinuation (primary endpoint: safety and side effects)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidents of rectal gonorrhea and chlamydia</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>New rectal gonorrhoea and chlamydia infections (primary endpoint: behavioral effects of PrEP use)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious adverse reactions</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>(primary endpoint: safety and side effects)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Approximately 18 months</time_frame>
    <description>Any adverse events leading to interruption or discontinuation of the study product (TRUVADA) (primary endpoint: safety and side effects)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">327</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Treatment group (TRUVADA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Homosexual men and heterosexual men and women at high risk of HIV infection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>emtricitabine/tenofovir disoproxil fumarate</intervention_name>
    <arm_group_label>Treatment group (TRUVADA)</arm_group_label>
    <other_name>TRUVADA</other_name>
    <other_name>FTC/TDF</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV negative at enrollment (per algorithm provided in protocol)&#xD;
&#xD;
          -  At high and ongoing risk for acquiring HIV infection (per algorithm provided in&#xD;
             protocol)&#xD;
&#xD;
          -  Aged 18 years or over&#xD;
&#xD;
          -  Resident of NSW (or elsewhere in Australia if they visit NSW with sufficient frequency&#xD;
             to allow participation)&#xD;
&#xD;
          -  Medicare eligible (to have Medicare coverage for the standard-of-care services)&#xD;
&#xD;
          -  Willing and able to provide informed consent&#xD;
&#xD;
          -  Willing and able to take part in all required study procedures&#xD;
&#xD;
          -  Proficiency in written and spoken English (necessary to complete attitude, behavioural&#xD;
             and lifestyle surveys)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infected or has symptoms consistent with acute viral infection (If HIV positive&#xD;
             status is not confirmed by testing, delay starting PrEP for at least one month and&#xD;
             reconfirm negative HIV-1 status).&#xD;
&#xD;
          -  Having an estimated creatinine clearance (glomerular filtration rate [GFR]) &lt;60ml/min&#xD;
&#xD;
          -  Having or developing clinical symptoms suggestive of lactic acidosis or pronounced&#xD;
             hepatotoxicity (including nausea, vomiting, unusual or unexpected stomach discomfort,&#xD;
             and weakness)&#xD;
&#xD;
          -  Concurrently taking a nephrotoxic agent (e.g., high-dose non-steroidal&#xD;
             anti-inflammatory drugs / NSAIDs)&#xD;
&#xD;
          -  Allergic to tenofovir disoproxil fumarate and/or emtricitabine (based on self-report&#xD;
             or recorded)&#xD;
&#xD;
          -  Concurrently taking prescribed products containing emtricitabine or tenofovir&#xD;
             disoproxil fumarate including ATRIPLA®, COMPLERA®, EMTRIVA, STRIBILD®, VIREAD; other&#xD;
             drugs containing lamivudine; HEPSERA&#xD;
&#xD;
          -  Mental health issues, memory loss or other cognitive impairment or intellectual&#xD;
             disability that may compromise participant safety and/or regimen adherence&#xD;
&#xD;
          -  Factors or conditions that may compromise a participant's retention in the study&#xD;
             (incarceration, planned relocation or potential absence from NSW for a period of 3&#xD;
             months or longer during the course of the study)&#xD;
&#xD;
          -  Unwilling to adhere to any of the required study procedures&#xD;
&#xD;
          -  Currently breastfeeding&#xD;
&#xD;
        Note: Safety for infants exposed to TRUVADA during pregnancy is not fully assessed but no&#xD;
        harm has been reported. Therefore, planning to become pregnant or currently being pregnant&#xD;
        is not an exclusion criterion for this study. However, women who are pregnant should learn&#xD;
        about the risks and benefits of TRUVADA to reduce the risk of acquiring HIV during their&#xD;
        pregnancy. Site investigators will review the risks and benefits of TRUVADA and of&#xD;
        potential HIV infection with pregnant women and women who plan to become pregnant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Iryna Zablotska, MD, MPH, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>The Kirby Institute for Infection and Immunity in Society</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>RPA Sexual Health</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holdsworth House Medical Practice</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital HIV, Immunology and Infectious Disease Unit</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Sydney Sexual Health Centre</name>
      <address>
        <city>Parramatta</city>
        <state>New South Wales</state>
        <zip>2150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sydney Sexual Health Centre</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>November 28, 2019</last_update_submitted>
  <last_update_submitted_qc>November 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>prevention</keyword>
  <keyword>prophylaxis</keyword>
  <keyword>antiretroviral</keyword>
  <keyword>biomedical</keyword>
  <keyword>bio-behavioural</keyword>
  <keyword>evaluation</keyword>
  <keyword>demonstration study</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
    <mesh_term>Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02206555
org study id: HEPP 1403
secondary id: 14/098
nct id: NCT02206555
lead sponsor: 
has dmc: Yes
Significant increases in HIV diagnoses among gay and other homosexually active men, in
      Australia and internationally, have been observed since the late 1990s. The levels of high
      HIV risk sexual practices among gay men have also increased, particularly unprotected anal
      intercourse (UAI). Nationally, over three quarters of the new HIV infections diagnosed
      annually are among men who have sex with men (MSM). The proportion of heterosexual men and
      women among those diagnosed with HIV annually has also increased in recent years. Despite
      successes in some situations, HIV transmission has not been adequately reduced by the
      prevention methods available to those at risk, such as education, condoms, and treatment of
      sexually transmitted infections (STIs).

      The effectiveness of daily oral antiretroviral medications (ARVs) as preexposure prophylaxis
      of HIV (PrEP) has now been established by clinical trials in both heterosexual adults and
      homosexual men. Whether PrEP confers high rates of protection in real life situations and is
      a feasible strategy to implement still requires further investigation. Through its "HIV
      prevention strategy 2015: New era," NSW Health committed to consider how to most
      appropriately and efficiently implement PrEP in line with evidence. This commitment
      translated in the support to this PrEP demonstration project.

      This demonstration project is designed to evaluate the off-label provision of daily
      combination of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC, known as TRUVADA) as
      PrEP to a sample of sero-negative individuals at high risk for HIV infection in clinical
      settings in New South Wales. The project will inform policy development regarding primary HIV
      prevention with PrEP.

      This is an open-label, single-arm treatment evaluation study. All consenting and eligible HIV
      negative participants will receive TRUVADA prescribed for daily administration orally. At
      each followup visit, the following procedures will be conducted: clinical evaluations/
      procedures, laboratory evaluations/ procedures, testing for HIV, STIs, hepatic and renal
      function, assessment for adherence to the prescribed medication, side effects, eligibility
      for next TRUVADA prescription, and willingness to continue on PrEP.

      As a study requirement, participants will be offered a self-administered assessment of
      behaviour, lifestyle and attitudes which will be conducted ideally within two and no more
      than seven days of the clinic visit in the participant's private space.

      Analyses will include: the feasibility of PrEP delivery, adherence to the study medication,
      safety and tolerability, the effects of PrEP use on behavior, and statistical analyses of the
      risk of HIV seroconversion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Time to accrual
time frame: Approximately 18 months
description: Time to accrual of 300 person-years of follow-up on TRUVADA. Each participant will receive TRUVADA for a maximum of 12 months, and will be followed for an additional three months after discontinuation. (Primary endpoint: feasibility of the process of PrEP delivery in health care settings in NSW)
measure: Seroconversion-free time on PrEP
time frame: Approximately 18 months
description: Seroconversion-free time on PrEP (Primary endpoint: feasibility of the process of PrEP delivery in health care settings in NSW)
measure: Time to TRUVADA discontinuation
time frame: Approximately 18 months
description: Time to TRUVADA discontinuation (primary endpoint: adherence)
measure: Prescribed doses taken
time frame: Approximately 18 months
description: Percentage of prescribed doses taken orally in the prescribed period (primary endpoint: adherence)
measure: Incidents of HIV seroconversion
time frame: Approximately 24 months
description: Incidence of HIV seroconversion among study participants during the course of their study participation and in six months following PrEP discontinuation (primary endpoint: safety and side effects)
measure: Incidents of rectal gonorrhea and chlamydia
time frame: Approximately 18 months
description: New rectal gonorrhoea and chlamydia infections (primary endpoint: behavioral effects of PrEP use)
measure: Serious adverse reactions
time frame: Approximately 18 months
description: (primary endpoint: safety and side effects)
measure: Adverse events
time frame: Approximately 18 months
description: Any adverse events leading to interruption or discontinuation of the study product (TRUVADA) (primary endpoint: safety and side effects)
arm group label: Treatment group (TRUVADA)
arm group type: Experimental
description: Homosexual men and heterosexual men and women at high risk of HIV infection
intervention type: Drug
intervention name: emtricitabine/tenofovir disoproxil fumarate
arm group label: Treatment group (TRUVADA)
other name: TRUVADA
other name: FTC/TDF
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Iryna Zablotska, MD, MPH, PhD
role: Study Chair
affiliation: The Kirby Institute for Infection and Immunity in Society
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Tenofovir
mesh term: Emtricitabine
mesh term: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination