<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/NCT03281135</url>
  </required_header>
  <id_info>
    <org_study_id>058/17/SPH</org_study_id>
    <nct_id>NCT03281135</nct_id>
  </id_info>
  <brief_title>Optimizing Cervical Cancer Screening Modalities</brief_title>
  <official_title>Optimizing Cervical Cancer Screening Modalities and Identifying the Molecular Epidemiology of Human Papilloma Virus in Ethiopia: A Cluster Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Addis Ababa University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Martin-Luther-Universität Halle-Wittenberg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Addis Ababa University</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 project aims to optimize cervical cancer screening adherence comparing Arm A (VIA) and&#xD;
      Arm B self-sampled Human Papilloma Virus (HPV) testing and determine the molecular&#xD;
      epidemiology of HPV, persistence level and identify factors responsible for persistence, and&#xD;
      also characterizing the potential dysplasia by biomarkers that describe the disease stage in&#xD;
      a population of Ethiopia.&#xD;
&#xD;
      A cluster-randomized trial will be used in this study. The total number of ten&#xD;
      kebele's(Smallest administrative unit) will be randomly classified in to two arms(VIA and&#xD;
      HPV+VIA).Community health workers will be used as a cluster for randomization. Community&#xD;
      sensitization and awareness creation will be performed at health facilities and in&#xD;
      communities at social, business or religious gatherings, about cervical cancer and its&#xD;
      prevention for eligible women in both arms. Women will be educated about cervical cancer and&#xD;
      advice for testing at the Hospital offering VIA (arm A). Women will also be instructed to&#xD;
      undergo HPV self-sampling at nearby health posts with a vaginal evalyn brush (arm B). All&#xD;
      eligible women on each cluster will be included in the study at both arms. Based on the&#xD;
      community health workers number and structure study area there will be about 22 clusters with&#xD;
      80 eligible women on each cluster. Brushes will be sent to the Microbiology Laboratory of&#xD;
      Department of Microbiology,Immunology and Parasitology,College of Health Sciences, Addis&#xD;
      Ababa University, Addis Ababa, where the laboratory service is sated-up . Trained&#xD;
      Microbiologists will perform the laboratory analysis at the HPV laboratory. Only women with&#xD;
      samples positive for high-risk HPV (hrHPV) will be contacted and informed to go to the&#xD;
      Hospital offering VIA. Further tests will also be performed from the brushes at the&#xD;
      collaborators' HPV laboratory, Germany to better characterize the dysplesia.&#xD;
&#xD;
      The women found positive for VIA or hrHPV+VIA will receive cryo treatment at Butajira&#xD;
      Hospital. To evaluate the long-term effect and factors for persistence, all eligible women&#xD;
      within the catchment area will be visited after 2 years door to-door and asked for a vaginal&#xD;
      self-sample and HPV-genotype test. The impact of intervention, factors associated with HPV&#xD;
      infection, persistence, clearance, and adherence to the screening service will be seen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cervical cancer is the second most common cancer in women worldwide but the commonest in&#xD;
      developing countries. In Ethiopia, cervical cancer is the leading cause of morbidity and&#xD;
      mortality from all cancers. The Human Papilloma Viruses (HPV) is a necessary cause for&#xD;
      cervical cancer (CC). HPVs 16, 18, 31, 33, 35 and 39 are considered as high risk types which&#xD;
      are mainly responsible in cervical carcinogenesis.&#xD;
&#xD;
      In developing countries, including Ethiopia, almost all women with cancers present to health&#xD;
      care facilities at late stages with advanced disease and poor prognosis. Unlike other&#xD;
      reproductive health cancers, cervical cancer can be prevented and even possible to be cured&#xD;
      if identified in its early stages. Currently cervical cancer screening by visual inspection&#xD;
      with acetic acid (VIA) and immediate treatment with cryotherapy is recommended by World&#xD;
      Health Organization(WHO) for low and middle income countries as this method does not require&#xD;
      especially trained professionals and more resources and results are available immediately&#xD;
      which reduces the attrition rate. However, yet accessing VIA is difficult for many rural&#xD;
      women as the service is only available at least at district Hospital level in very few&#xD;
      places. Although VIA is accepted by the government in many low income countries, training ,&#xD;
      maintaining quality assurance, the invasiveness of a pelvic examination and user variability&#xD;
      of the test remain critical barriers. Moreover, the short comings of this method includes&#xD;
      having of low positive predictive value and lack of evidence on periodic screening&#xD;
      performance.&#xD;
&#xD;
      Detection of High risk Human Papilloma Viruses (HrHPV) in the cervix has been recommended in&#xD;
      settings wherever possible. World Health Organization (WHO) primarily recommends the HPV test&#xD;
      which is very sensitive and a convenient molecular test for cervical cancer screening. This&#xD;
      approach is found to be less examiner-dependent, reduce the burden in health system, enhance&#xD;
      the accuracy, efficiency and reduce cultural barriers. Therefore, HPV test might be a future&#xD;
      option in low and middle income countries.&#xD;
&#xD;
      In Ethiopia, screening with VIA followed by cryotherapy started in 2009 first for women with&#xD;
      HIV in selected 14 hospitals and subsequently the service was expanded to 10 additional&#xD;
      health institution. Currently the federal ministry of health in Ethiopia has scaled up the&#xD;
      service to the general public into public health facilities. However, still majority of women&#xD;
      in Ethiopia are residing in rural area where access to screening and treatment facilities is&#xD;
      limited or lacking.&#xD;
&#xD;
      So far few studies have been conducted in African settings for assessing the uptake and&#xD;
      acceptability of independent screening approaches. Study in Sub Saharan Africa reported&#xD;
      higher acceptance of HPV based cervical cancer screening than visual inspection with acetic&#xD;
      acid. In Ethiopia there is no adequate information on women uptake, acceptability, adherence&#xD;
      and potential barriers of cervical cancer screening for different screening modalities.&#xD;
      Moreover, data on HPV prevalence and genotype distribution are rare.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 2018</start_date>
  <completion_date type="Anticipated">May 2019</completion_date>
  <primary_completion_date type="Anticipated">May 2019</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>
    <intervention_model_description>A cluster randomized trial will be conducted in the Health and Demographic Surveillance Site (HDSS) of Addis Ababa University, School of Public Health which is located in Butajira district. The study population consists of women aged 30-49 who are found among the catchment population of ten Kebele's(Smallest Administrative Unit). Each Kebele will have 2 or more clusters based on the community health workers structure and size. A total of 22 clusters will then be randomized in to two arms. A total of 1760 women will be grouped in to 22 clusters, each comprises 80 women.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adherence to the procedures</measure>
    <time_frame>With in 1 year period</time_frame>
    <description>Proportions of women who adhered in the screening and subsequent follow up based on HPV testing using self-sampling versus an offer of attending for a VIA.&#xD;
This will be compared based on: A women who accessed the HPV self sampling at health post and accessed VIA and treated for positive result plus untreated for negative result divided by the eligible women in the arm versus A women who accessed the VIA at health facility and treated for positive result plus untreated for negative result divided by the eligible women in the arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of women that participate in Cervical Cancer Screening in the control (VIA) compared with the number of women that participate in the intervention(Self sampling HPV testing)</measure>
    <time_frame>With in 1 year period</time_frame>
    <description>This will be measured based on the number of women who attended only the screening procedure after the first sensitization program</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Demographic and socio cultural factors associated with uptake and adherence of two different cervical cancer screening procedures</measure>
    <time_frame>With in 1 year period</time_frame>
    <description>Here we will try to identify and explore socio economic and cultural barriers related with each screening approach.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HPV genotypes among rural women</measure>
    <time_frame>With in 1 year period</time_frame>
    <description>We will identify HPV genotypes from all collected samples of the study population. Samples will be collected from the community and analyzed centrally in Addis Ababa.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1760</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>HPV testing</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This is an experimental arm for the primary outcome, 'adherence to the procedures'. In this group self sampling will be done using the Evalyn brush for HPV testing.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care: VIA screening</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Control Arm, in which women's are invited to cervical cancer screening as per standard Ethiopian cervical cancer prevention and control guideline. Uptake of screening in this group will be compared with the HPV testing arm group to test for significant differences in adherence.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HPV testing</intervention_name>
    <description>Clusters randomly allocated to this arm of the study will be sensitized to be showed up in nearby health posts for self sampling with Evalyn brush for HPV testing.</description>
    <arm_group_label>HPV testing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women aged between 30 and 49&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  women with History of hysterectomy or cervical cancer, pregnant women, not meet the&#xD;
             eligibility criteria and unable to give consent.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>September 12, 2017</last_update_submitted>
  <last_update_submitted_qc>September 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Addis Ababa University</investigator_affiliation>
    <investigator_full_name>Muluken Gizaw Turago</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Cervical cancer screening</keyword>
  <keyword>Adherance</keyword>
  <keyword>HPV typing</keyword>
  <keyword>HDSS</keyword>
  <keyword>Ethiopia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>We will see</ipd_description>
  </patient_data>
  <!-- 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/NCT03281135
org study id: 058/17/SPH
nct id: NCT03281135
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This project aims to optimize cervical cancer screening adherence comparing Arm A (VIA) and
      Arm B self-sampled Human Papilloma Virus (HPV) testing and determine the molecular
      epidemiology of HPV, persistence level and identify factors responsible for persistence, and
      also characterizing the potential dysplasia by biomarkers that describe the disease stage in
      a population of Ethiopia.

      A cluster-randomized trial will be used in this study. The total number of ten
      kebele's(Smallest administrative unit) will be randomly classified in to two arms(VIA and
      HPV+VIA).Community health workers will be used as a cluster for randomization. Community
      sensitization and awareness creation will be performed at health facilities and in
      communities at social, business or religious gatherings, about cervical cancer and its
      prevention for eligible women in both arms. Women will be educated about cervical cancer and
      advice for testing at the Hospital offering VIA (arm A). Women will also be instructed to
      undergo HPV self-sampling at nearby health posts with a vaginal evalyn brush (arm B). All
      eligible women on each cluster will be included in the study at both arms. Based on the
      community health workers number and structure study area there will be about 22 clusters with
      80 eligible women on each cluster. Brushes will be sent to the Microbiology Laboratory of
      Department of Microbiology,Immunology and Parasitology,College of Health Sciences, Addis
      Ababa University, Addis Ababa, where the laboratory service is sated-up . Trained
      Microbiologists will perform the laboratory analysis at the HPV laboratory. Only women with
      samples positive for high-risk HPV (hrHPV) will be contacted and informed to go to the
      Hospital offering VIA. Further tests will also be performed from the brushes at the
      collaborators' HPV laboratory, Germany to better characterize the dysplesia.

      The women found positive for VIA or hrHPV+VIA will receive cryo treatment at Butajira
      Hospital. To evaluate the long-term effect and factors for persistence, all eligible women
      within the catchment area will be visited after 2 years door to-door and asked for a vaginal
      self-sample and HPV-genotype test. The impact of intervention, factors associated with HPV
      infection, persistence, clearance, and adherence to the screening service will be seen.
Cervical cancer is the second most common cancer in women worldwide but the commonest in
      developing countries. In Ethiopia, cervical cancer is the leading cause of morbidity and
      mortality from all cancers. The Human Papilloma Viruses (HPV) is a necessary cause for
      cervical cancer (CC). HPVs 16, 18, 31, 33, 35 and 39 are considered as high risk types which
      are mainly responsible in cervical carcinogenesis.

      In developing countries, including Ethiopia, almost all women with cancers present to health
      care facilities at late stages with advanced disease and poor prognosis. Unlike other
      reproductive health cancers, cervical cancer can be prevented and even possible to be cured
      if identified in its early stages. Currently cervical cancer screening by visual inspection
      with acetic acid (VIA) and immediate treatment with cryotherapy is recommended by World
      Health Organization(WHO) for low and middle income countries as this method does not require
      especially trained professionals and more resources and results are available immediately
      which reduces the attrition rate. However, yet accessing VIA is difficult for many rural
      women as the service is only available at least at district Hospital level in very few
      places. Although VIA is accepted by the government in many low income countries, training ,
      maintaining quality assurance, the invasiveness of a pelvic examination and user variability
      of the test remain critical barriers. Moreover, the short comings of this method includes
      having of low positive predictive value and lack of evidence on periodic screening
      performance.

      Detection of High risk Human Papilloma Viruses (HrHPV) in the cervix has been recommended in
      settings wherever possible. World Health Organization (WHO) primarily recommends the HPV test
      which is very sensitive and a convenient molecular test for cervical cancer screening. This
      approach is found to be less examiner-dependent, reduce the burden in health system, enhance
      the accuracy, efficiency and reduce cultural barriers. Therefore, HPV test might be a future
      option in low and middle income countries.

      In Ethiopia, screening with VIA followed by cryotherapy started in 2009 first for women with
      HIV in selected 14 hospitals and subsequently the service was expanded to 10 additional
      health institution. Currently the federal ministry of health in Ethiopia has scaled up the
      service to the general public into public health facilities. However, still majority of women
      in Ethiopia are residing in rural area where access to screening and treatment facilities is
      limited or lacking.

      So far few studies have been conducted in African settings for assessing the uptake and
      acceptability of independent screening approaches. Study in Sub Saharan Africa reported
      higher acceptance of HPV based cervical cancer screening than visual inspection with acetic
      acid. In Ethiopia there is no adequate information on women uptake, acceptability, adherence
      and potential barriers of cervical cancer screening for different screening modalities.
      Moreover, data on HPV prevalence and genotype distribution are rare.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A cluster randomized trial will be conducted in the Health and Demographic Surveillance Site (HDSS) of Addis Ababa University, School of Public Health which is located in Butajira district. The study population consists of women aged 30-49 who are found among the catchment population of ten Kebele's(Smallest Administrative Unit). Each Kebele will have 2 or more clusters based on the community health workers structure and size. A total of 22 clusters will then be randomized in to two arms. A total of 1760 women will be grouped in to 22 clusters, each comprises 80 women.
primary purpose: Screening
masking: None (Open Label)
measure: Adherence to the procedures
time frame: With in 1 year period
description: Proportions of women who adhered in the screening and subsequent follow up based on HPV testing using self-sampling versus an offer of attending for a VIA.
This will be compared based on: A women who accessed the HPV self sampling at health post and accessed VIA and treated for positive result plus untreated for negative result divided by the eligible women in the arm versus A women who accessed the VIA at health facility and treated for positive result plus untreated for negative result divided by the eligible women in the arm.
measure: Number of women that participate in Cervical Cancer Screening in the control (VIA) compared with the number of women that participate in the intervention(Self sampling HPV testing)
time frame: With in 1 year period
description: This will be measured based on the number of women who attended only the screening procedure after the first sensitization program
measure: Demographic and socio cultural factors associated with uptake and adherence of two different cervical cancer screening procedures
time frame: With in 1 year period
description: Here we will try to identify and explore socio economic and cultural barriers related with each screening approach.
measure: HPV genotypes among rural women
time frame: With in 1 year period
description: We will identify HPV genotypes from all collected samples of the study population. Samples will be collected from the community and analyzed centrally in Addis Ababa.
arm group label: HPV testing
arm group type: Other
description: This is an experimental arm for the primary outcome, 'adherence to the procedures'. In this group self sampling will be done using the Evalyn brush for HPV testing.
arm group label: Standard care: VIA screening
arm group type: No Intervention
description: Control Arm, in which women's are invited to cervical cancer screening as per standard Ethiopian cervical cancer prevention and control guideline. Uptake of screening in this group will be compared with the HPV testing arm group to test for significant differences in adherence.
intervention type: Other
intervention name: HPV testing
description: Clusters randomly allocated to this arm of the study will be sensitized to be showed up in nearby health posts for self sampling with Evalyn brush for HPV testing.
arm group label: HPV testing
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Principal Investigator
investigator affiliation: Addis Ababa University
investigator full name: Muluken Gizaw Turago
investigator title: Assistant Professor
mesh term: Uterine Cervical Neoplasms
sharing ipd: Undecided
ipd description: We will see