<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/NCT01723956</url>
  </required_header>
  <id_info>
    <org_study_id>ZA.09.0265</org_study_id>
    <nct_id>NCT01723956</nct_id>
  </id_info>
  <brief_title>Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women</brief_title>
  <acronym>VICAR2</acronym>
  <official_title>Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Witwatersrand, South Africa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Witwatersrand, South Africa</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the efficacy of cryotherapy and large loop excision of the transformation zone&#xD;
      (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia&#xD;
      (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and Human Papillomavirus.&#xD;
&#xD;
      Hypothesis: LEEP will be more effective than cryotherapy in removing CIN 2/3 lesions in HIV&#xD;
      positive women in South Africa&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cervical cancer is the most common cancer in HIV positive women. This is due to&#xD;
      immunosuppression and lack of organized and effective screening and treatment programs in&#xD;
      Africa. Other screening and treatment modalities need to be evaluated in resource limited&#xD;
      countries as there is not capacity in most of these countries to implement a&#xD;
      cytology/histology based program. The treatment modality of cryotherapy is easy to train and&#xD;
      perform and can be done by a nurse. LEEP requires significant training usually doctors and&#xD;
      skills in administering local anaesthetic. This study compares the two modalities of&#xD;
      cryotherapy vs LEEP in a randomized controlled study in HIV positive women in South Africa.&#xD;
&#xD;
      A. PRIMARY AIMS (S.A.):&#xD;
&#xD;
        1. To compare the efficacy of cryotherapy and large loop excision of the transformation&#xD;
           zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial&#xD;
           neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.&#xD;
&#xD;
        2. To determine the utility of subsequent HPV DNA testing as a marker of effective&#xD;
           treatment following the treatment of CIN 2/3 among HIV-seropositive women.&#xD;
&#xD;
        3. To compare the safety of cryotherapy versus LLETZ in HIV seropositive women.&#xD;
&#xD;
      SECONDARY AIMS:&#xD;
&#xD;
      1. To describe HIV disease status (CD4, HIV viral load), demographics, and sexual behavior in&#xD;
      each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.&#xD;
&#xD;
      3. To determine the cervical disease recurrence rates with cryotherapy and LLETZ.&#xD;
&#xD;
      4. To evaluate the relationship between HIV status, demographics, HPV, and sexual behavior&#xD;
      with the clearance of cervical disease at the ectocervical and endocervical margins in HIV&#xD;
      seropositive women.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2010</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Compare efficacy of cryotherapy and LEEP</measure>
    <time_frame>1 year</time_frame>
    <description>To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The ability to use Human Papillomavirus as the measure of treatment success</measure>
    <time_frame>1 year</time_frame>
    <description>To determine the utility of subsequent HPV DNA testing as a marker of effective treatment following the treatment of CIN 2/3 among HIV-seropositive women.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the safety of cryotherapy versus LLETZ in HIV seropositive women</measure>
    <time_frame>1 month, 6 months and 12 months</time_frame>
    <description>To compare the safety of cryotherapy versus LLETZ in HIV seropositive women by evaluating adverse events as measured by the Division of AIDS toxicity table 2004 (revised August 2010)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Describe factors associated with successful treatment of CIN 2/3</measure>
    <time_frame>1 year</time_frame>
    <description>To describe HIV disease status (CD4, HIV viral load), demographics, tissue margins and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the cervical disease recurrence rates with cryotherapy and LLETZ.</measure>
    <time_frame>6 months and 12 months</time_frame>
    <description>To determine the cervical disease recurrence rates with cryotherapy and LLETZ at 6 months and 12 months by colposcopy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">166</enrollment>
  <condition>Cervical Intraepithelial Neoplasia</condition>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>LEEP treatment of CIN 2/3 cervical lesion in HIV positive women (standard of Care)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cryotherapy treatment of CIN 2/3 cervical lesions</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cryotherapy</intervention_name>
    <description>This is involves freezing the lesions with a cryo gun using Nitrous Oxide for 3 minutes-- wait 5 minutes and then refreezing for 3 more minutes. This procedure uses the Wallach cryogun</description>
    <arm_group_label>Arm A</arm_group_label>
    <other_name>This is a study using Freezing with a cryogun</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>LEEP</intervention_name>
    <description>The cervix is anaesthetized with lidocaine and then a electric loop is applied to the cervical lesion which is cut with one pass. The LEEP machine used is the automatic Finesse Machine.</description>
    <arm_group_label>Arm B</arm_group_label>
    <other_name>Loop Electric Excision Procedure</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women 18-65 years of age&#xD;
&#xD;
          -  Not menstruating (if menstruating, the patient can be screened at another date)&#xD;
&#xD;
          -  Able to sign consent&#xD;
&#xD;
          -  Able to follow the study protocol&#xD;
&#xD;
          -  HIV positive (by two different criteria; either 2 different rapid HPV tests of&#xD;
             different manufacturers, a HIV viral load ≥5,000,ELISA, Western blot documented in&#xD;
             VICAR 1)&#xD;
&#xD;
          -  Participant with histology-proven CIN 2 or 3 disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Clinically active sexually transmitted disease determined by clinical history and/or&#xD;
             physical exam (may participate after adequate treatment by syndromic treatment&#xD;
             management)&#xD;
&#xD;
          -  Known and previous treatment for high grade squamouse intraepithelial lesion by any&#xD;
             method (cryotherapy, LLETZ or cone biopsy)&#xD;
&#xD;
          -  Previous hysterectomy with removal of the cervix&#xD;
&#xD;
          -  Significant medical illness/mental illness that the investigator feels would prevent&#xD;
             the participant from complying with the protocol or place the participant at medical&#xD;
             risk&#xD;
&#xD;
          -  Cervical dysplastic lesions that are not appropriate for cryotherapy, defined as the&#xD;
             following:&#xD;
&#xD;
               1. Lesion is greater than ≥75% cervix&#xD;
&#xD;
               2. Lesion entering into the cervical canal and the complete lesion cannot be&#xD;
                  visualized&#xD;
&#xD;
               3. Presence of abnormal vasculature&#xD;
&#xD;
               4. Lesion bigger that the cryotherapy probe&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cynthia S Firnhaber, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Witwatersrand, South Africa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helen Joseph Hospital</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2092</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>September 19, 2014</last_update_submitted>
  <last_update_submitted_qc>September 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 22, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Witwatersrand, South Africa</investigator_affiliation>
    <investigator_full_name>Cynthia S Firnhaber</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Cervical Dysplasia</keyword>
  <keyword>Cin 2</keyword>
  <keyword>Cin 3</keyword>
  <keyword>HIV positive women</keyword>
  <keyword>South Africa</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Seropositivity</mesh_term>
    <mesh_term>Uterine Cervical Dysplasia</mesh_term>
  </condition_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/NCT01723956
org study id: ZA.09.0265
nct id: NCT01723956
lead sponsor: 
has dmc: Yes
To compare the efficacy of cryotherapy and large loop excision of the transformation zone
      (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia
      (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and Human Papillomavirus.

      Hypothesis: LEEP will be more effective than cryotherapy in removing CIN 2/3 lesions in HIV
      positive women in South Africa
Cervical cancer is the most common cancer in HIV positive women. This is due to
      immunosuppression and lack of organized and effective screening and treatment programs in
      Africa. Other screening and treatment modalities need to be evaluated in resource limited
      countries as there is not capacity in most of these countries to implement a
      cytology/histology based program. The treatment modality of cryotherapy is easy to train and
      perform and can be done by a nurse. LEEP requires significant training usually doctors and
      skills in administering local anaesthetic. This study compares the two modalities of
      cryotherapy vs LEEP in a randomized controlled study in HIV positive women in South Africa.

      A. PRIMARY AIMS (S.A.):

        1. To compare the efficacy of cryotherapy and large loop excision of the transformation
           zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial
           neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.

        2. To determine the utility of subsequent HPV DNA testing as a marker of effective
           treatment following the treatment of CIN 2/3 among HIV-seropositive women.

        3. To compare the safety of cryotherapy versus LLETZ in HIV seropositive women.

      SECONDARY AIMS:

      1. To describe HIV disease status (CD4, HIV viral load), demographics, and sexual behavior in
      each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.

      3. To determine the cervical disease recurrence rates with cryotherapy and LLETZ.

      4. To evaluate the relationship between HIV status, demographics, HPV, and sexual behavior
      with the clearance of cervical disease at the ectocervical and endocervical margins in HIV
      seropositive women.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Compare efficacy of cryotherapy and LEEP
time frame: 1 year
description: To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.
measure: The ability to use Human Papillomavirus as the measure of treatment success
time frame: 1 year
description: To determine the utility of subsequent HPV DNA testing as a marker of effective treatment following the treatment of CIN 2/3 among HIV-seropositive women.
measure: To compare the safety of cryotherapy versus LLETZ in HIV seropositive women
time frame: 1 month, 6 months and 12 months
description: To compare the safety of cryotherapy versus LLETZ in HIV seropositive women by evaluating adverse events as measured by the Division of AIDS toxicity table 2004 (revised August 2010)
measure: Describe factors associated with successful treatment of CIN 2/3
time frame: 1 year
description: To describe HIV disease status (CD4, HIV viral load), demographics, tissue margins and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.
measure: To determine the cervical disease recurrence rates with cryotherapy and LLETZ.
time frame: 6 months and 12 months
description: To determine the cervical disease recurrence rates with cryotherapy and LLETZ at 6 months and 12 months by colposcopy
arm group label: Arm B
arm group type: Active Comparator
description: LEEP treatment of CIN 2/3 cervical lesion in HIV positive women (standard of Care)
arm group label: Arm A
arm group type: Experimental
description: Cryotherapy treatment of CIN 2/3 cervical lesions
intervention type: Procedure
intervention name: Cryotherapy
description: This is involves freezing the lesions with a cryo gun using Nitrous Oxide for 3 minutes-- wait 5 minutes and then refreezing for 3 more minutes. This procedure uses the Wallach cryogun
arm group label: Arm A
other name: This is a study using Freezing with a cryogun
intervention type: Procedure
intervention name: LEEP
description: The cervix is anaesthetized with lidocaine and then a electric loop is applied to the cervical lesion which is cut with one pass. The LEEP machine used is the automatic Finesse Machine.
arm group label: Arm B
other name: Loop Electric Excision Procedure
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Cynthia S Firnhaber, MD
role: Principal Investigator
affiliation: University of Witwatersrand, South Africa
facility: 
country: South Africa
responsible party type: Principal Investigator
investigator affiliation: University of Witwatersrand, South Africa
investigator full name: Cynthia S Firnhaber
investigator title: Associate Professor of Medicine
mesh term: HIV Seropositivity
mesh term: Uterine Cervical Dysplasia