<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/NCT03832023</url>
  </required_header>
  <id_info>
    <org_study_id>EG0211</org_study_id>
    <nct_id>NCT03832023</nct_id>
  </id_info>
  <brief_title>Community-based Tuberculosis Tracing and Preventive Therapy</brief_title>
  <acronym>CONTACT</acronym>
  <official_title>Community Intervention for Tuberculosis Active Contact Tracing and Preventive Therapy - a Cluster Randomized Study (CONTACT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Elizabeth Glaser Pediatric AIDS Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Epicentre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Sheffield</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut de Recherche pour le Developpement</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Elizabeth Glaser Pediatric AIDS Foundation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The many gaps observed in the cascade of care of tuberculosis (TB) child contacts occur&#xD;
      mostly in the screening, preventive therapy (PT) initiation and PT completion steps and the&#xD;
      main drivers of these gaps are considered to be the health system infrastructure, limited&#xD;
      worker resources and parents' reluctance to bring their children to the facility for&#xD;
      screening. There would be great advantages of using a symptom-based screening at community&#xD;
      level where only the symptomatic contacts are referred to hospital for further evaluation and&#xD;
      asymptomatic contacts are started on PT in the community. Household or community-based&#xD;
      screening is likely to improve the uptake and acceptability of child contact screening and&#xD;
      management as well as adherence to PT and to reduce cost and workload at facility level.&#xD;
&#xD;
      This study proposes to compare the cascade of care between two models for TB screening and&#xD;
      management of household TB child contacts in two high TB burden and limited resource&#xD;
      countries, Cameroon and Uganda. In the facility-based model, children will be screened at&#xD;
      facility (Cameroon) or household level (Uganda) and preventive therapy initiation, refills of&#xD;
      PT therapy and follow-up will be done at facility level. In the intervention group&#xD;
      (community-based model), child contacts will be screened in the household by a community&#xD;
      health worker (CHW). Those with symptoms suggestive of TB will be referred to the facility&#xD;
      for TB investigations. Asymptomatic child contacts from high risk groups (under-5 years or&#xD;
      HIV infected 5-14) will be initiated on PT (3 months isoniazid-rifampicin) in the household.&#xD;
      Refills of PT therapy will also be done in the communities by the CHW. In both models,&#xD;
      symptomatic children requiring further investigations for TB diagnosis will be referred to a&#xD;
      health facility.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary study objective is to compare the proportion of household child TB contacts&#xD;
      eligible for PT (under-5 years and HIV-infected children 5-14 years without active TB) who&#xD;
      initiate and complete PT using facility-based and decentralized community-based models of&#xD;
      care for contact screening and management.&#xD;
&#xD;
      Secondary objectives are:&#xD;
&#xD;
        1. To compare the facility and community-based models in terms of:&#xD;
&#xD;
             -  The full cascade of care for the initiation and completion of PT in child TB&#xD;
                contacts &lt; 5 years or HIV+ children 5-14 years .&#xD;
&#xD;
             -  Cascade of care for the detection and treatment of TB in child contacts (all ages):&#xD;
&#xD;
             -  PT tolerability and adherence among eligible child contacts initiated on PT.&#xD;
&#xD;
             -  Treatment uptake and outcomes for child contacts diagnosed with TB .&#xD;
&#xD;
             -  Child contact outcomes at 6 months after enrollment for all child contacts.&#xD;
&#xD;
             -  Acceptability by the parents/guardians, health personnel and community of the&#xD;
                different models of care.&#xD;
&#xD;
             -  Cost and cost-effectiveness of the different models.&#xD;
&#xD;
             -  Fidelity of the implementation of the model activities as compared to the protocol.&#xD;
&#xD;
        2. To assess the number of adult contact cases diagnosed with TB through the&#xD;
           community-based screening.&#xD;
&#xD;
        3. To compare between the pre- (baseline assessment) and post-intervention (by model of&#xD;
           care) data related to:&#xD;
&#xD;
             -  Children diagnosed with TB and registered at facility level and their treatment&#xD;
                outcome.&#xD;
&#xD;
             -  Adults diagnosed with TB and registered at facility level and their treatment&#xD;
                outcome.&#xD;
&#xD;
             -  PT initiation and outcomes.&#xD;
&#xD;
      This study will be implemented under the frame of the Catalyzing Pediatric TB Innovation (CaP&#xD;
      TB) Project, funded by Unitaid and implemented by the Elizabeth Glaser Pediatric AIDS&#xD;
      Foundation (EGPAF). The goal of CaP TB is to improve the pediatric TB morbidity and mortality&#xD;
      by catalyzing the wide uptake of the new first-line fixed dose combination drugs for children&#xD;
      and optimizing the use of these drugs through improved case detection and innovative models&#xD;
      of care. In both models of care, contacts with TB suggestive symptoms will be investigated&#xD;
      for TB at the cluster facility that is supported by EGPAF within the CaP TB project. In&#xD;
      Cameroon the CaP TB project will be implemented in the Central and Littoral regions and in&#xD;
      Uganda in the South-West region.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2019</start_date>
  <completion_date type="Actual">August 1, 2022</completion_date>
  <primary_completion_date type="Actual">August 1, 2022</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>Clusters were selected among facilities participating in the first phase of the CAP-TB project following an initial facility assessment for participating in the CAP-TB project. Facilities with diagnostic and treatment capacity and detecting and minimum of 50 bacteriologically confirmed pulmonary TB cases per year in a rural/semi-rural or semi-urban setting were selected. The facilities correspond to district hospitals in Cameroon and health center IV or district hospitals in Uganda.&#xD;
Twenty clusters will be randomized between the intervention and the facility-based model. The randomization unit (cluster) will be the facility where TB cases (index cases) are diagnosed and its catchment area.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Completion of preventive therapy</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of child TB contacts &lt;5 years of age and HIV-infected children of 5-14 years of age who initiate and complete the PT of all child contacts &lt;5 years of age and HIV-infected children of 5-14 years of age declared by the index case</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of children screened</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children screened among child contacts &lt;5 years or HIV-infected 5-14 years declared by the index case</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children eligible for PT</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children eligible for PT among screened children</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children started on PT</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children started on PT among those eligible for PT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children who did not complete PT</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children who did not complete PT among those started on PT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children with presumptive TB</measure>
    <time_frame>1 month</time_frame>
    <description>Number of children with symptoms suggestive of TB among screened children (&lt; 15 years)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children investigated for TB</measure>
    <time_frame>1 month</time_frame>
    <description>Number of children with presumptive TB investigated for TB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children diagnosed with TB</measure>
    <time_frame>1 month</time_frame>
    <description>Number of children diagnosed with TB among those with symptoms suggestive of TB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children started on TB treatment</measure>
    <time_frame>1 month</time_frame>
    <description>Number of children with TB diagnosis who are started on TB treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of adult contacts screened</measure>
    <time_frame>1 month</time_frame>
    <description>Number of adult contacts screened among household identified adult contacts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of adults presumptive TB cases</measure>
    <time_frame>1 month</time_frame>
    <description>Number of adults with symptoms suggestive of TB among those screened for TB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of adults diagnosed with TB</measure>
    <time_frame>1 month</time_frame>
    <description>Number of adults presumptive TB cases diagnosed with TB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children with serious adverse events</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children with serious adverse events among children started on PT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children with adverse event of interest</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children with adverse event of interest (peripheral neuropathy, clinical hepatotoxicity) among children on PT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment adherence</measure>
    <time_frame>6 months</time_frame>
    <description>Ratio of PT dose taken by the child over the total number of doses prescribed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment outcomes of children started on TB treatment</measure>
    <time_frame>6 months</time_frame>
    <description>Cured&#xD;
Treatment completed&#xD;
Failure&#xD;
Death&#xD;
Lost to follow up&#xD;
Transferred out</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children diagnosed with TB</measure>
    <time_frame>6 months</time_frame>
    <description>Number of children diagnosed with TB after initiation of PT or children not initiated on PT and not diagnosed with TB at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TB case detection during pre-intervention period</measure>
    <time_frame>2 years</time_frame>
    <description>Number of patients registered in the facility TB register one year before intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children among all registered TB cases during pre-intervention period</measure>
    <time_frame>2 years</time_frame>
    <description>Number of children among all patients diagnosed with TB and registered in the facility TB register one year before intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TB treatment outcome of registered TB patients during pre-intervention period</measure>
    <time_frame>2 years</time_frame>
    <description>Cured&#xD;
Treatment completed&#xD;
Failure&#xD;
Death&#xD;
Lost to follow up&#xD;
Transferred out</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of children started on PT during pre-intervention period</measure>
    <time_frame>2 years</time_frame>
    <description>Number of children started on PT from the facility PT register one year before intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Completion rate of children started on PT intervention during pre-intervention period</measure>
    <time_frame>2 years</time_frame>
    <description>Number of children who completed PT among those started on PT from the facility PT register one year before</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of household visits by CHW</measure>
    <time_frame>2 years</time_frame>
    <description>Number of visits by the CHW to the household for contact screening per household</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of parents/guardians who accept household visit</measure>
    <time_frame>2 years</time_frame>
    <description>Acceptability of household visit for contact screening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reasons of refusal of household visit</measure>
    <time_frame>2 years</time_frame>
    <description>Description of screening failures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preference for household visit versus facility visit</measure>
    <time_frame>2 years</time_frame>
    <description>This outcome measures whether the parent/guardian prefers bringing child to the facility rather than having someone coming to his household</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Critical events experienced by CHW during household visit</measure>
    <time_frame>2 years</time_frame>
    <description>Description of critical events during house visit and how these where dealt with</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transport cost for household visit by CHW</measure>
    <time_frame>2 years</time_frame>
    <description>Cost of transportation for the CHW to go from the health facility to a household</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transport cost for parents/guardian for facility-based screening</measure>
    <time_frame>2 years</time_frame>
    <description>Cost supported by families to bring child contact to the facility for screening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time spent to perform household contact screening visit</measure>
    <time_frame>2 years</time_frame>
    <description>It includes the time to reach the household, the time spent in the household and the time to go back to the facility for CHW</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of delivered activities compared to the intended activities of the model</measure>
    <time_frame>2 years</time_frame>
    <description>This outcome will assess fidelity to study procedures</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1400</enrollment>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Facility-based model</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care of each country</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Community-based model</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Screening and initiating preventive therapy in communities</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Screening and initiating preventive therapy in communities</intervention_name>
    <description>Symptom-based screening of tuberculosis household child contacts by community health workers; initiation of preventive therapy (3 months of a fixed-dose combination of rifampicin-isoniazid or 6 months isoniazid for HIV+ children on protease inhibitors) in the household by a nurse; follow-up of children under preventive therapy by a community health worker for eligible children at community level, and referral of presumptive tuberculosis cases (children and adults) to the facility.</description>
    <arm_group_label>Community-based model</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inclusion of the index cases&#xD;
&#xD;
               -  Age &gt; 15 years&#xD;
&#xD;
               -  Newly bacteriologically confirmed TB case (less than a month since diagnosis)&#xD;
&#xD;
               -  Reports child contact(s)&#xD;
&#xD;
               -  Written informed consent signed by the index case and by parents/guardians for&#xD;
                  minors or incapacitated people&#xD;
&#xD;
          -  Inclusion of contacts&#xD;
&#xD;
               -  Household contact&#xD;
&#xD;
               -  Age&#xD;
&#xD;
               -  Facility-based model in Cameroon: &lt; 5 years or HIV infected 5-14 years and all&#xD;
                  self-referred adults or children*.&#xD;
&#xD;
               -  Facility-based model in Uganda and community-based model on both countries: all&#xD;
                  ages&#xD;
&#xD;
               -  Written informed consent signed by adult contacts and by parents/guardians for&#xD;
                  minors or incapacitated people&#xD;
&#xD;
               -  Written assent for children &gt; 7 years in Cameroon and ≥8 years in Uganda&#xD;
&#xD;
        Under the facility-based model in Cameroon, although there is no systematic request to&#xD;
        screen adults or HIV-negative child contacts 5-14 years old, first inclusions showed that&#xD;
        some of them came by themselves for TB screening. This justifies their inclusion in the&#xD;
        study in order to ensure the completeness of data for all contacts screened under the&#xD;
        facility-based model.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Exclusion of index cases&#xD;
&#xD;
          -  Index cases who do not have child household contacts living in the catchment area of&#xD;
             one of the study clusters&#xD;
&#xD;
          -  Index cases diagnosed with rifampicin resistance, multidrug-resistant (MDR) or&#xD;
             extensively drug-resistant (XDR) TB *Index cases from a household screened within the&#xD;
             CONTACT study and that does not declare child contacts from another household.*&#xD;
&#xD;
          -  Index cases that are prisoners&#xD;
&#xD;
        TB confirmed adult contacts cases living in the same household as an index case already&#xD;
        enrolled in the study will not be included as new index cases unless they declare&#xD;
        additional contacts from another household&#xD;
&#xD;
        - Exclusion of the contacts&#xD;
&#xD;
          -  If the contact is already on PT or on TB treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boris Tchounga, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Elisabeth Glaser Pediatric AIDS Foundation</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daniel Atwine, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Epicentre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital de district Bonassama</name>
      <address>
        <city>Bonabéri</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district Log-Baba</name>
      <address>
        <city>Douala</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Médical d'arrondissement Delangue</name>
      <address>
        <city>Edéa</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district Mbalmayo</name>
      <address>
        <city>Mbalmayo</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district Mfou</name>
      <address>
        <city>Mfou</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital régional Nkongsamba</name>
      <address>
        <city>Nkongsamba</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district Okola</name>
      <address>
        <city>Okola</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district Olembe</name>
      <address>
        <city>Olembe</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district St Jean de Malte</name>
      <address>
        <city>Penja</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de district Yoko</name>
      <address>
        <city>Yoko</city>
        <country>Cameroon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ishongororo HC IV</name>
      <address>
        <city>Ibanda</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruhoko HC IV</name>
      <address>
        <city>Ibanda</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kabwohe Clinical Research Center HC II</name>
      <address>
        <city>Kabwohe</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kabwohe HC IV</name>
      <address>
        <city>Kabwohe</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kitagata Hospital</name>
      <address>
        <city>Kitagata</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bubaare HC III</name>
      <address>
        <city>Mbarara</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bwizibwera HC IV</name>
      <address>
        <city>Mbarara</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kakoba HC III</name>
      <address>
        <city>Mbarara</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mbarara Municipal Council HC IV</name>
      <address>
        <city>Mbarara</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bwongyera HC III</name>
      <address>
        <city>Ntungamo</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Itojo Hospital</name>
      <address>
        <city>Ntungamo</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kitwe HC IV</name>
      <address>
        <city>Ntungamo</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ntungamo Ngoma HC III</name>
      <address>
        <city>Ntungamo</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rubaare HC IV</name>
      <address>
        <city>Ntungamo</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rwashamaire HC IV</name>
      <address>
        <city>Ntungamo</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Cameroon</country>
    <country>Uganda</country>
  </location_countries>
  <reference>
    <citation>Mandalakas AM, Kirchner HL, Walzl G, Gie RP, Schaaf HS, Cotton MF, Grewal HM, Hesseling AC. Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting. Am J Respir Crit Care Med. 2015 Apr 1;191(7):820-30. doi: 10.1164/rccm.201406-1165OC.</citation>
    <PMID>25622087</PMID>
  </reference>
  <reference>
    <citation>Rutherford ME, Hill PC, Triasih R, Sinfield R, van Crevel R, Graham SM. Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions. Trop Med Int Health. 2012 Oct;17(10):1264-73. doi: 10.1111/j.1365-3156.2012.03053.x. Epub 2012 Aug 5.</citation>
    <PMID>22862994</PMID>
  </reference>
  <reference>
    <citation>Triasih R, Robertson CF, Duke T, Graham SM. A prospective evaluation of the symptom-based screening approach to the management of children who are contacts of tuberculosis cases. Clin Infect Dis. 2015 Jan 1;60(1):12-8. doi: 10.1093/cid/ciu748. Epub 2014 Sep 30.</citation>
    <PMID>25270649</PMID>
  </reference>
  <reference>
    <citation>Mandalakas AM, Hesseling AC, Gie RP, Schaaf HS, Marais BJ, Sinanovic E. Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting. Thorax. 2013 Mar;68(3):247-55. doi: 10.1136/thoraxjnl-2011-200933. Epub 2012 Jun 20.</citation>
    <PMID>22717944</PMID>
  </reference>
  <reference>
    <citation>Szkwarko D, Hirsch-Moverman Y, Du Plessis L, Du Preez K, Carr C, Mandalakas AM. Child contact management in high tuberculosis burden countries: A mixed-methods systematic review. PLoS One. 2017 Aug 1;12(8):e0182185. doi: 10.1371/journal.pone.0182185. eCollection 2017.</citation>
    <PMID>28763500</PMID>
  </reference>
  <reference>
    <citation>Graham SM. The management of infection with Mycobacterium tuberculosis in young children post-2015: an opportunity to close the policy-practice gap. Expert Rev Respir Med. 2017 Jan;11(1):41-49. doi: 10.1080/17476348.2016.1267572. Epub 2016 Dec 10.</citation>
    <PMID>27910720</PMID>
  </reference>
  <reference>
    <citation>Egere U, Sillah A, Togun T, Kandeh S, Cole F, Jallow A, Able-Thomas A, Hoelscher M, Heinrich N, Hill PC, Kampmann B. Isoniazid preventive treatment among child contacts of adults with smear-positive tuberculosis in The Gambia. Public Health Action. 2016 Dec 21;6(4):226-231. doi: 10.5588/pha.16.0073.</citation>
    <PMID>28123958</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institut de Recherche pour le Developpement</investigator_affiliation>
    <investigator_full_name>Maryline Bonnet</investigator_full_name>
    <investigator_title>Research Director, MD PhD</investigator_title>
  </responsible_party>
  <keyword>Children</keyword>
  <keyword>Contact tracing</keyword>
  <keyword>Preventive therapy</keyword>
  <keyword>Prophylaxis</keyword>
  <keyword>Community health workers</keyword>
  <keyword>Community-based distribution</keyword>
  <keyword>Standard of care</keyword>
  <keyword>Screening</keyword>
  <keyword>Randomized controlled trial</keyword>
  <keyword>Cameroon</keyword>
  <keyword>Uganda</keyword>
  <keyword>Patient outcome assessment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03832023
org study id: EG0211
nct id: NCT03832023
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The many gaps observed in the cascade of care of tuberculosis (TB) child contacts occur
      mostly in the screening, preventive therapy (PT) initiation and PT completion steps and the
      main drivers of these gaps are considered to be the health system infrastructure, limited
      worker resources and parents' reluctance to bring their children to the facility for
      screening. There would be great advantages of using a symptom-based screening at community
      level where only the symptomatic contacts are referred to hospital for further evaluation and
      asymptomatic contacts are started on PT in the community. Household or community-based
      screening is likely to improve the uptake and acceptability of child contact screening and
      management as well as adherence to PT and to reduce cost and workload at facility level.

      This study proposes to compare the cascade of care between two models for TB screening and
      management of household TB child contacts in two high TB burden and limited resource
      countries, Cameroon and Uganda. In the facility-based model, children will be screened at
      facility (Cameroon) or household level (Uganda) and preventive therapy initiation, refills of
      PT therapy and follow-up will be done at facility level. In the intervention group
      (community-based model), child contacts will be screened in the household by a community
      health worker (CHW). Those with symptoms suggestive of TB will be referred to the facility
      for TB investigations. Asymptomatic child contacts from high risk groups (under-5 years or
      HIV infected 5-14) will be initiated on PT (3 months isoniazid-rifampicin) in the household.
      Refills of PT therapy will also be done in the communities by the CHW. In both models,
      symptomatic children requiring further investigations for TB diagnosis will be referred to a
      health facility.
The primary study objective is to compare the proportion of household child TB contacts
      eligible for PT (under-5 years and HIV-infected children 5-14 years without active TB) who
      initiate and complete PT using facility-based and decentralized community-based models of
      care for contact screening and management.

      Secondary objectives are:

        1. To compare the facility and community-based models in terms of:

             -  The full cascade of care for the initiation and completion of PT in child TB
                contacts < 5 years or HIV+ children 5-14 years .

             -  Cascade of care for the detection and treatment of TB in child contacts (all ages):

             -  PT tolerability and adherence among eligible child contacts initiated on PT.

             -  Treatment uptake and outcomes for child contacts diagnosed with TB .

             -  Child contact outcomes at 6 months after enrollment for all child contacts.

             -  Acceptability by the parents/guardians, health personnel and community of the
                different models of care.

             -  Cost and cost-effectiveness of the different models.

             -  Fidelity of the implementation of the model activities as compared to the protocol.

        2. To assess the number of adult contact cases diagnosed with TB through the
           community-based screening.

        3. To compare between the pre- (baseline assessment) and post-intervention (by model of
           care) data related to:

             -  Children diagnosed with TB and registered at facility level and their treatment
                outcome.

             -  Adults diagnosed with TB and registered at facility level and their treatment
                outcome.

             -  PT initiation and outcomes.

      This study will be implemented under the frame of the Catalyzing Pediatric TB Innovation (CaP
      TB) Project, funded by Unitaid and implemented by the Elizabeth Glaser Pediatric AIDS
      Foundation (EGPAF). The goal of CaP TB is to improve the pediatric TB morbidity and mortality
      by catalyzing the wide uptake of the new first-line fixed dose combination drugs for children
      and optimizing the use of these drugs through improved case detection and innovative models
      of care. In both models of care, contacts with TB suggestive symptoms will be investigated
      for TB at the cluster facility that is supported by EGPAF within the CaP TB project. In
      Cameroon the CaP TB project will be implemented in the Central and Littoral regions and in
      Uganda in the South-West region.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Clusters were selected among facilities participating in the first phase of the CAP-TB project following an initial facility assessment for participating in the CAP-TB project. Facilities with diagnostic and treatment capacity and detecting and minimum of 50 bacteriologically confirmed pulmonary TB cases per year in a rural/semi-rural or semi-urban setting were selected. The facilities correspond to district hospitals in Cameroon and health center IV or district hospitals in Uganda.
Twenty clusters will be randomized between the intervention and the facility-based model. The randomization unit (cluster) will be the facility where TB cases (index cases) are diagnosed and its catchment area.
primary purpose: Health Services Research
masking: None (Open Label)
measure: Completion of preventive therapy
time frame: 6 months
description: Proportion of child TB contacts <5 years of age and HIV-infected children of 5-14 years of age who initiate and complete the PT of all child contacts <5 years of age and HIV-infected children of 5-14 years of age declared by the index case
measure: Proportion of children screened
time frame: 6 months
description: Number of children screened among child contacts <5 years or HIV-infected 5-14 years declared by the index case
measure: Proportion of children eligible for PT
time frame: 6 months
description: Number of children eligible for PT among screened children
measure: Proportion of children started on PT
time frame: 6 months
description: Number of children started on PT among those eligible for PT
measure: Proportion of children who did not complete PT
time frame: 6 months
description: Number of children who did not complete PT among those started on PT
measure: Proportion of children with presumptive TB
time frame: 1 month
description: Number of children with symptoms suggestive of TB among screened children (< 15 years)
measure: Proportion of children investigated for TB
time frame: 1 month
description: Number of children with presumptive TB investigated for TB
measure: Proportion of children diagnosed with TB
time frame: 1 month
description: Number of children diagnosed with TB among those with symptoms suggestive of TB
measure: Proportion of children started on TB treatment
time frame: 1 month
description: Number of children with TB diagnosis who are started on TB treatment
measure: Proportion of adult contacts screened
time frame: 1 month
description: Number of adult contacts screened among household identified adult contacts
measure: Proportion of adults presumptive TB cases
time frame: 1 month
description: Number of adults with symptoms suggestive of TB among those screened for TB
measure: Proportion of adults diagnosed with TB
time frame: 1 month
description: Number of adults presumptive TB cases diagnosed with TB
measure: Proportion of children with serious adverse events
time frame: 6 months
description: Number of children with serious adverse events among children started on PT
measure: Proportion of children with adverse event of interest
time frame: 6 months
description: Number of children with adverse event of interest (peripheral neuropathy, clinical hepatotoxicity) among children on PT
measure: Treatment adherence
time frame: 6 months
description: Ratio of PT dose taken by the child over the total number of doses prescribed
measure: Treatment outcomes of children started on TB treatment
time frame: 6 months
description: Cured
Treatment completed
Failure
Death
Lost to follow up
Transferred out
measure: Proportion of children diagnosed with TB
time frame: 6 months
description: Number of children diagnosed with TB after initiation of PT or children not initiated on PT and not diagnosed with TB at baseline
measure: TB case detection during pre-intervention period
time frame: 2 years
description: Number of patients registered in the facility TB register one year before intervention
measure: Proportion of children among all registered TB cases during pre-intervention period
time frame: 2 years
description: Number of children among all patients diagnosed with TB and registered in the facility TB register one year before intervention
measure: TB treatment outcome of registered TB patients during pre-intervention period
time frame: 2 years
description: Cured
Treatment completed
Failure
Death
Lost to follow up
Transferred out
measure: Number of children started on PT during pre-intervention period
time frame: 2 years
description: Number of children started on PT from the facility PT register one year before intervention
measure: Completion rate of children started on PT intervention during pre-intervention period
time frame: 2 years
description: Number of children who completed PT among those started on PT from the facility PT register one year before
measure: Number of household visits by CHW
time frame: 2 years
description: Number of visits by the CHW to the household for contact screening per household
measure: Proportion of parents/guardians who accept household visit
time frame: 2 years
description: Acceptability of household visit for contact screening
measure: Reasons of refusal of household visit
time frame: 2 years
description: Description of screening failures
measure: Preference for household visit versus facility visit
time frame: 2 years
description: This outcome measures whether the parent/guardian prefers bringing child to the facility rather than having someone coming to his household
measure: Critical events experienced by CHW during household visit
time frame: 2 years
description: Description of critical events during house visit and how these where dealt with
measure: Transport cost for household visit by CHW
time frame: 2 years
description: Cost of transportation for the CHW to go from the health facility to a household
measure: Transport cost for parents/guardian for facility-based screening
time frame: 2 years
description: Cost supported by families to bring child contact to the facility for screening
measure: Time spent to perform household contact screening visit
time frame: 2 years
description: It includes the time to reach the household, the time spent in the household and the time to go back to the facility for CHW
measure: Proportion of delivered activities compared to the intended activities of the model
time frame: 2 years
description: This outcome will assess fidelity to study procedures
arm group label: Facility-based model
arm group type: No Intervention
description: Standard of care of each country
arm group label: Community-based model
arm group type: Experimental
description: Screening and initiating preventive therapy in communities
intervention type: Other
intervention name: Screening and initiating preventive therapy in communities
description: Symptom-based screening of tuberculosis household child contacts by community health workers; initiation of preventive therapy (3 months of a fixed-dose combination of rifampicin-isoniazid or 6 months isoniazid for HIV+ children on protease inhibitors) in the household by a nurse; follow-up of children under preventive therapy by a community health worker for eligible children at community level, and referral of presumptive tuberculosis cases (children and adults) to the facility.
arm group label: Community-based model
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Boris Tchounga, MD, PHD
role: Principal Investigator
affiliation: Elisabeth Glaser Pediatric AIDS Foundation
last name: Daniel Atwine, MD, PhD
role: Principal Investigator
affiliation: Epicentre
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Cameroon
country: Uganda
citation: Mandalakas AM, Kirchner HL, Walzl G, Gie RP, Schaaf HS, Cotton MF, Grewal HM, Hesseling AC. Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting. Am J Respir Crit Care Med. 2015 Apr 1;191(7):820-30. doi: 10.1164/rccm.201406-1165OC.
PMID: 25622087
citation: Rutherford ME, Hill PC, Triasih R, Sinfield R, van Crevel R, Graham SM. Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions. Trop Med Int Health. 2012 Oct;17(10):1264-73. doi: 10.1111/j.1365-3156.2012.03053.x. Epub 2012 Aug 5.
PMID: 22862994
citation: Triasih R, Robertson CF, Duke T, Graham SM. A prospective evaluation of the symptom-based screening approach to the management of children who are contacts of tuberculosis cases. Clin Infect Dis. 2015 Jan 1;60(1):12-8. doi: 10.1093/cid/ciu748. Epub 2014 Sep 30.
PMID: 25270649
citation: Mandalakas AM, Hesseling AC, Gie RP, Schaaf HS, Marais BJ, Sinanovic E. Modelling the cost-effectiveness of strategies to prevent tuberculosis in child contacts in a high-burden setting. Thorax. 2013 Mar;68(3):247-55. doi: 10.1136/thoraxjnl-2011-200933. Epub 2012 Jun 20.
PMID: 22717944
citation: Szkwarko D, Hirsch-Moverman Y, Du Plessis L, Du Preez K, Carr C, Mandalakas AM. Child contact management in high tuberculosis burden countries: A mixed-methods systematic review. PLoS One. 2017 Aug 1;12(8):e0182185. doi: 10.1371/journal.pone.0182185. eCollection 2017.
PMID: 28763500
citation: Graham SM. The management of infection with Mycobacterium tuberculosis in young children post-2015: an opportunity to close the policy-practice gap. Expert Rev Respir Med. 2017 Jan;11(1):41-49. doi: 10.1080/17476348.2016.1267572. Epub 2016 Dec 10.
PMID: 27910720
citation: Egere U, Sillah A, Togun T, Kandeh S, Cole F, Jallow A, Able-Thomas A, Hoelscher M, Heinrich N, Hill PC, Kampmann B. Isoniazid preventive treatment among child contacts of adults with smear-positive tuberculosis in The Gambia. Public Health Action. 2016 Dec 21;6(4):226-231. doi: 10.5588/pha.16.0073.
PMID: 28123958
responsible party type: Principal Investigator
investigator affiliation: Institut de Recherche pour le Developpement
investigator full name: Maryline Bonnet
investigator title: Research Director, MD PhD
mesh term: Tuberculosis
sharing ipd: No