<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/NCT01721798</url>
  </required_header>
  <id_info>
    <org_study_id>10369</org_study_id>
    <nct_id>NCT01721798</nct_id>
  </id_info>
  <brief_title>Comparison of Two IUDs Among Cape Town HIV-positive Women</brief_title>
  <official_title>Comparison of Two IUDs Among Cape Town HIV-positive Women: A Randomized Controlled Trial Assessing Safety of Registered Products in South Africa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>FHI 360</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Cape Town</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>City University of New York, School of Public Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>FHI 360</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will inform international medical guidelines as to whether the Levonorgestrel&#xD;
      intrauterine device (LNG IUD), a highly effective long-acting reversible contraceptive&#xD;
      method, is safe and acceptable as compared to the copper intrauterine device (C-IUD) for&#xD;
      HIV-positive women in Cape Town, South Africa. If the LNG IUD is found to be safe and&#xD;
      acceptable, the introduction of this method to HIV positive women in developing countries&#xD;
      could significantly reduce unplanned pregnancy and mother-to-child transmission of HIV, and&#xD;
      confer non-contraceptive benefits to HIV-positive women in Sub-Saharan Africa.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design: Single site, double-blind, randomized controlled trial&#xD;
&#xD;
      Population: HIV-positive South African women between the ages of 18 and 40 years&#xD;
&#xD;
      Study size: At least 166 women&#xD;
&#xD;
      Study intervention: Levonorgestrel intrauterine device (LNG IUD) or the copper T-380&#xD;
      intrauterine device (C-IUD)&#xD;
&#xD;
      Duration &amp; Follow-up: Approximately 48 months in total. Recruitment will take approximately&#xD;
      24 months. After enrollment, each participant will be followed for 24 months.&#xD;
&#xD;
      Primary Objectives: To compare LNG IUD safety to the safety of the C-IUD with respect to&#xD;
      genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the&#xD;
      presence and absence of ART.&#xD;
&#xD;
      Secondary Objectives: 1) To compare LNG IUD safety to the safety of the C-IUD with respect to&#xD;
      HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two&#xD;
      pre-ART study arms. 2) To explore LNG IUD safety with respect to non-HIV related outcomes,&#xD;
      including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic&#xD;
      inflammatory disease (PID). 3) To measure LNG IUD acceptability through device continuation&#xD;
      and other measures for the LNG IUD as compared to the C-IUD. 4) To compare three genital&#xD;
      tract sampling methods to determine which provides optimal recovery of HIV RNA and immune&#xD;
      mediators over a series of three visits.&#xD;
&#xD;
      Primary Endpoints: Change in detection and quantity of HIV RNA genital VL measures between&#xD;
      study arms at baseline and 6 months, and over 24 months following IUD insertion.&#xD;
&#xD;
      Secondary Endpoints: 1) Measures of HIV disease progression, including CD4 change, time to&#xD;
      ART initiation, and mean plasma VL change from baseline to 6 and through 24 months among&#xD;
      pre-ART women. 2) Hemoglobin change and incidence of STIs and PID for all participants&#xD;
      through 24 months. 3) IUD continuation and expulsion rates between study arms comparing&#xD;
      different IUDs over a 24-month period and acceptability measures through quantitative and&#xD;
      qualitative methods. 4) Comparison of female genital tract sampling methods for recovery of&#xD;
      HIV RNA as measured by VL and immune mediators (e.g. cytokines).&#xD;
&#xD;
      Study Site: Gugulethu Community Health Centre (GCHC), Cape Town, South Africa&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 10, 2013</start_date>
  <completion_date type="Actual">July 13, 2018</completion_date>
  <primary_completion_date type="Actual">July 13, 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>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Compare LNG IUD safety to the safety of the C-IUD with respect to genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the presence and absence of ART.</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare LNG IUD safety to the safety of the C-IUD with respect to HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two pre-ART study arms.</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Explore LNG IUD safety with respect to non-HIV related outcomes, including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic inflammatory disease (PID).</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure LNG IUD acceptability through device continuation and other measures for the LNG IUD as compared to the C-IUD.</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare three genital tract sampling methods to determine which provides optimal recovery of HIV RNA and immune mediators over a series of three visits.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">205</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Copper T-380a IUD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Copper T-380a IUD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mirena Levonorgestrel IUD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mirena levonorgestrel IUD</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mirena levonorgestrel IUD</intervention_name>
    <description>Intrauterine contraception system</description>
    <arm_group_label>Mirena Levonorgestrel IUD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Copper T-380a IUD</intervention_name>
    <description>intrauterine contraception system</description>
    <arm_group_label>Copper T-380a IUD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Willing and able to provide written informed consent (IC) to be screened for and to&#xD;
             participate in the trial&#xD;
&#xD;
          -  Interested and willing to use the IUD as a family planning method.&#xD;
&#xD;
          -  Between 18 to 40 years of age (inclusive): This age range includes women during their&#xD;
             years of greatest fertility and 18 is the age of majority for research consent in&#xD;
             South Africa.&#xD;
&#xD;
          -  Willing to participate in all aspects of the study and to comply with study procedures&#xD;
             and visits, for 24 months, including:&#xD;
&#xD;
               -  Be randomized&#xD;
&#xD;
               -  Adhere to follow-up schedule and willing to be contacted by site staff between&#xD;
                  study visits (by phone and/or in person)&#xD;
&#xD;
               -  Provide contact/locator information&#xD;
&#xD;
               -  Agree for site staff to review clinic chart to confirm HIV status&#xD;
&#xD;
          -  Has documented HIV infection&#xD;
&#xD;
          -  For pre-ART entrants:&#xD;
&#xD;
               -  ART-ineligible at screening, based on current South African ART guidelines&#xD;
&#xD;
               -  Be at least 6 months post-delivery and not pregnant or desiring pregnancy for the&#xD;
                  next 30 months.&#xD;
&#xD;
          -  For ART-using entrants:&#xD;
&#xD;
               -  ART-use demonstrated by clinical records reflecting laboratory measures&#xD;
                  consistent with ART use and evidence of viral suppression (plasma VL&lt;1000&#xD;
                  copies/mL) at the most recent VL measure.&#xD;
&#xD;
               -  Be at least 6 weeks post-delivery and not pregnant or desiring pregnancy for the&#xD;
                  next 30 months.&#xD;
&#xD;
          -  Intending residence in Cape Town area for next 30 months&#xD;
&#xD;
          -  No documented or known history of infertility or sterilization&#xD;
&#xD;
          -  No gross evidence of cervical neoplasia on examination&#xD;
&#xD;
          -  No prior history of ectopic pregnancy&#xD;
&#xD;
          -  No history of or suspected hormonally-dependent neoplasm or undiagnosed abnormal&#xD;
             vaginal bleeding&#xD;
&#xD;
          -  Local language fluency and comprehension&#xD;
&#xD;
          -  Not participating in any other clinical trial with a biomedical intervention&#xD;
&#xD;
          -  Have no condition that, based on the opinion of the Site PI, would preclude provision&#xD;
             of informed consent, make participation in the study unsafe, or complicate&#xD;
             interpretation of data.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>B Landon Myer, MBChB, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cape Town</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Catherine Todd, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>FHI 360</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Cape Town</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape Province</state>
        <zip>7701</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>August 17, 2018</last_update_submitted>
  <last_update_submitted_qc>August 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AE adverse event</keyword>
  <keyword>AIDS acquired immunodeficiency syndrome</keyword>
  <keyword>ALT (SGPT) alanine aminotransferase</keyword>
  <keyword>ART antiretroviral therapy</keyword>
  <keyword>AST (SGOT) aspartate aminotransferase</keyword>
  <keyword>DCF data collection forms</keyword>
  <keyword>DMC Data Monitoring Committee</keyword>
  <keyword>FDA (U.S.) Food and Drug Administration</keyword>
  <keyword>GCP Good Clinical Practice guidelines</keyword>
  <keyword>HB sAg Hepatitis B surface antigen</keyword>
  <keyword>ICH International Council for Harmonization</keyword>
  <keyword>IND Investigational New Drug Application</keyword>
  <keyword>IRB Institutional Review Board</keyword>
  <keyword>IU International units</keyword>
  <keyword>mg milligram(s)</keyword>
  <keyword>mm3 cubic millimeter(s)</keyword>
  <keyword>PCR polymerase chain reaction</keyword>
  <keyword>SAE serious adverse event</keyword>
  <keyword>µg microgram</keyword>
  <keyword>ULN upper limit of the normal range</keyword>
  <keyword>WB Western Blot</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Seropositivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Copper</mesh_term>
    <mesh_term>Levonorgestrel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 16, 2022</submitted>
    <returned>March 31, 2023</returned>
    <submitted>May 30, 2023</submitted>
  </pending_results>
  <!-- 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/NCT01721798
org study id: 10369
nct id: NCT01721798
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study will inform international medical guidelines as to whether the Levonorgestrel
      intrauterine device (LNG IUD), a highly effective long-acting reversible contraceptive
      method, is safe and acceptable as compared to the copper intrauterine device (C-IUD) for
      HIV-positive women in Cape Town, South Africa. If the LNG IUD is found to be safe and
      acceptable, the introduction of this method to HIV positive women in developing countries
      could significantly reduce unplanned pregnancy and mother-to-child transmission of HIV, and
      confer non-contraceptive benefits to HIV-positive women in Sub-Saharan Africa.
Design: Single site, double-blind, randomized controlled trial

      Population: HIV-positive South African women between the ages of 18 and 40 years

      Study size: At least 166 women

      Study intervention: Levonorgestrel intrauterine device (LNG IUD) or the copper T-380
      intrauterine device (C-IUD)

      Duration & Follow-up: Approximately 48 months in total. Recruitment will take approximately
      24 months. After enrollment, each participant will be followed for 24 months.

      Primary Objectives: To compare LNG IUD safety to the safety of the C-IUD with respect to
      genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the
      presence and absence of ART.

      Secondary Objectives: 1) To compare LNG IUD safety to the safety of the C-IUD with respect to
      HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two
      pre-ART study arms. 2) To explore LNG IUD safety with respect to non-HIV related outcomes,
      including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic
      inflammatory disease (PID). 3) To measure LNG IUD acceptability through device continuation
      and other measures for the LNG IUD as compared to the C-IUD. 4) To compare three genital
      tract sampling methods to determine which provides optimal recovery of HIV RNA and immune
      mediators over a series of three visits.

      Primary Endpoints: Change in detection and quantity of HIV RNA genital VL measures between
      study arms at baseline and 6 months, and over 24 months following IUD insertion.

      Secondary Endpoints: 1) Measures of HIV disease progression, including CD4 change, time to
      ART initiation, and mean plasma VL change from baseline to 6 and through 24 months among
      pre-ART women. 2) Hemoglobin change and incidence of STIs and PID for all participants
      through 24 months. 3) IUD continuation and expulsion rates between study arms comparing
      different IUDs over a 24-month period and acceptability measures through quantitative and
      qualitative methods. 4) Comparison of female genital tract sampling methods for recovery of
      HIV RNA as measured by VL and immune mediators (e.g. cytokines).

      Study Site: Gugulethu Community Health Centre (GCHC), Cape Town, South Africa
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Compare LNG IUD safety to the safety of the C-IUD with respect to genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the presence and absence of ART.
time frame: 24 months
measure: Compare LNG IUD safety to the safety of the C-IUD with respect to HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two pre-ART study arms.
time frame: 24 months
measure: Explore LNG IUD safety with respect to non-HIV related outcomes, including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic inflammatory disease (PID).
time frame: 24 months
measure: Measure LNG IUD acceptability through device continuation and other measures for the LNG IUD as compared to the C-IUD.
time frame: 24 months
measure: Compare three genital tract sampling methods to determine which provides optimal recovery of HIV RNA and immune mediators over a series of three visits.
time frame: 6 months
arm group label: Copper T-380a IUD
arm group type: Active Comparator
description: Copper T-380a IUD
arm group label: Mirena Levonorgestrel IUD
arm group type: Active Comparator
description: Mirena levonorgestrel IUD
intervention type: Device
intervention name: Mirena levonorgestrel IUD
description: Intrauterine contraception system
arm group label: Mirena Levonorgestrel IUD
intervention type: Device
intervention name: Copper T-380a IUD
description: intrauterine contraception system
arm group label: Copper T-380a IUD
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: B Landon Myer, MBChB, PhD
role: Principal Investigator
affiliation: University of Cape Town
last name: Catherine Todd, MD, MPH
role: Principal Investigator
affiliation: FHI 360
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: HIV Seropositivity
mesh term: Copper
mesh term: Levonorgestrel
sharing ipd: No
submitted: June 16, 2022
returned: March 31, 2023
submitted: May 30, 2023