<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/NCT03028129</url>
  </required_header>
  <id_info>
    <org_study_id>U1111-1189-0829</org_study_id>
    <nct_id>NCT03028129</nct_id>
  </id_info>
  <brief_title>Prevention of Tuberculosis in Prisons</brief_title>
  <official_title>Primary Prophylaxis for Prevention of TB in Prison's Populations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal University of Mato Grosso</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oswaldo Cruz Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Federal University of Mato Grosso</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 purpose of this study is to determine if the isoniazid is effective in the prevention of&#xD;
      tuberculosis in a prison population, exposed to the high endemicity of the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite being a known disease of mankind over 9000 years, tuberculosis (TB) is still a major&#xD;
      public health problem in developing countries, mainly due to so-called highly endemic sites,&#xD;
      such as prisons.&#xD;
&#xD;
      It is Infectious disease, with airborne transmission, TB can present both the active or&#xD;
      latent form. Despite the biological aspect of transmission, unhealthy environmental&#xD;
      conditions (room without direct sunlight, poor ventilation and overcrowded) and individual&#xD;
      factors (malnutrition, immunosuppression, use of alcohol and other drugs) have significant&#xD;
      influence on transferability and infectivity.&#xD;
&#xD;
      With the discovery of drugs active against Mycobacterium tuberculosis, it was observed a&#xD;
      reduction of disease incidence in the world. Despite this declining incidence, World Health&#xD;
      Organization (WHO) classifies TB as a public health problem due to the emergence of multidrug&#xD;
      strains or extensively resistant to treatment, added to the cases of latent TB reactivation,&#xD;
      observed with the advent of HIV/AIDS.&#xD;
&#xD;
      Studies show a direct relationship between the incidence of TB and the prison environment.&#xD;
      Nevertheless, the presence of prisons in one location increases the incidence of this&#xD;
      disease, indicating that there is an exchange of disease between the prison and the&#xD;
      community.&#xD;
&#xD;
      Currently, control of TB in the prison system is based on the tracking of individuals with&#xD;
      active TB and / or latent and, in their respective treatment. For the identification of&#xD;
      individuals with active disease, it is necessary the recognition of respiratory symptoms&#xD;
      (cough mainly) and sputum smear microscopy and sputum culture, and chest X-ray. As the search&#xD;
      of individuals with latent form, must be carried to the skin test with Purified Protein&#xD;
      Derived (PPD).&#xD;
&#xD;
      Most of the units of the Brazilian's prison system these diagnostic methods are not available&#xD;
      and hence the transport of individuals for their realization is necessary, generating an&#xD;
      additional cost, in most cases, unfeasible process execution.&#xD;
&#xD;
      With the completion of this study, it seek to determine the effectiveness of primary&#xD;
      prophylaxis in the prison population in order to gather new scientific evidence, to bring&#xD;
      affordable methods for the control of TB in prisons.&#xD;
&#xD;
      Despite advances in diagnosis and treatment TB, this is the third leading cause of death from&#xD;
      infectious diseases worldwide (Naghavi et al, 2015). In 2015, the WHO estimated incidence of&#xD;
      9.6 million new cases of TB in the world, with about 1.1 million deaths. For Brazil it was&#xD;
      estimated incidence of 44 cases per 100,000 (WHO, 2015). The incidence of TB has declined&#xD;
      about 2% per year, but this rate is not homogeneous in the global context.&#xD;
&#xD;
      Brazil occupies the 22nd place in the ranking of the WHO with an estimated annual rate of&#xD;
      83,310 cases of the disease (Zumla et al, 2015). In the past seven years, it is estimated&#xD;
      that the incidence declined only 0.7% (per year). A key factor in this slow progress in TB&#xD;
      control in Brazil, and other emerging countries is the existence of high-risk subpopulations,&#xD;
      including slums and prisons, which act as reservoirs and amplifiers for the transmission of&#xD;
      the disease (Basu; Stückler; Mckee 2011; Dowdy et al, 2012). A recent systematic review&#xD;
      showed that the average incidence of TB in the prison population can be up to 23 times that&#xD;
      recorded in the general population (Baussano et al, 2010).&#xD;
&#xD;
      With the fourth largest prison populations in the world, is observed in Brazil, the increased&#xD;
      incidence of TB among prisoners in the last seven years. Although prisoners represent only&#xD;
      0.3% of the population, the increase in the prison population over this period resulted in&#xD;
      almost doubling the proportion of all TB cases that occur among prisoners (4.1% in 2007, 8,&#xD;
      1% in 2013).&#xD;
&#xD;
      The arrests are in an ideal environment for the spread of TB, since they show individuals&#xD;
      users of tobacco and alcohol in high doses, in addition to drug abuse in overcrowded cells&#xD;
      with poor ventilation and with limited access to care health and diagnosis of TB. Currently,&#xD;
      the Ministry of Health recommends active search for TB at the entrance to the prison and once&#xD;
      a year by chest X-ray. Due to the cost and logistics, most prisons do not adhere to this&#xD;
      recommendation. There is also a clear recommendation not to use the tuberculin skin test or&#xD;
      perform the treatment for latent tuberculosis. If the procedures for active case detection&#xD;
      and / or prophylactic treatment would impact the high transmission in prisons is a question&#xD;
      that still remains open (Al-Darraji; Kamarulzamn; Altice, 2012).&#xD;
&#xD;
      The concentration of cases of TB in prisons can represent both an obstacle and an opportunity&#xD;
      to control the disease, depending on the effectiveness of interventions in these&#xD;
      environments.&#xD;
&#xD;
      Preliminary studies show high annual rate of TB infection (26%) among the prison population&#xD;
      of 12 penitentiaries of Mato Grosso do Sul. Besides the large burden of disease in this&#xD;
      population is significant dispersion of the TB prison to the community (Sacchi et al, 2015).&#xD;
      Cross-sectional studies show high yield annual screening for TB, however, the effectiveness&#xD;
      of this measure combined with other interventions remains unclear (Ferreira et al, 1996;&#xD;
      Fournet et al, 2006; Lemos et al, 2014; Vieira et al, 2010; Sanches et al, 2013; Walnut;&#xD;
      Abrahão; Galesi, 2012; Kuhleis et al, 2012; Estevan; Oliveira; Croda, 2013). Due to the&#xD;
      combination of high force of infection in prisons and short prison term, primary prophylaxis&#xD;
      may be an effective intervention. This new approach has never been evaluated in the context&#xD;
      of prisons in low and middle income countries; to assess the impact of program strategies for&#xD;
      TB screening and prophylaxis, longitudinal data will be essential. Given the infrastructure&#xD;
      that was created for long-term prospective studies in Brazil, there is an excellent&#xD;
      opportunity to close the critical knowledge gaps that have been barriers to effective&#xD;
      implementation of TB control in high transmission prisons.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Interim analysis showed efficacy less than 2.5%.&#xD;
  </why_stopped>
  <start_date type="Actual">September 4, 2017</start_date>
  <completion_date type="Actual">August 10, 2019</completion_date>
  <primary_completion_date type="Actual">August 10, 2019</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.</measure>
    <time_frame>up to 6 months</time_frame>
    <description>Number of participants who had a Quantiferon TB Gold Plus (QIAGEN®) score greater than or equal to 0.35 international units per milliliter, at the time of the premature exclusion visit, on all participants in the group.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">467</enrollment>
  <condition>Tuberculosis, Pulmonary</condition>
  <condition>Antibiotic Prophylaxis</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoniazid 900 milligrams</intervention_name>
    <description>Oral tablet, with the isoniazid 900mg, given two weekly. The administration will be supervised.</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Antibiotic Treatment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral tablet, without the active ingredient, similar in size, weight, color, taste and odor.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Placebo Treatment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Age above 18 and under 45 at the time of inclusion;&#xD;
&#xD;
          -  Sign the informed consent form.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Be indigenous;&#xD;
&#xD;
          -  Active TB or previous use of isoniazid;&#xD;
&#xD;
          -  Score Alcohol Use Disorders Identification Test ≥15.&#xD;
&#xD;
          -  Reactive serology for HIV, hepatitis B and C;&#xD;
&#xD;
          -  Reactive result for quantiferon, considering as positive the result of Tube 1 and / or&#xD;
             Tube22 above 0.2 IU / mL;&#xD;
&#xD;
          -  Liver enzymes (Aspartate aminotransferase and Alanate aminotransferase) three times&#xD;
             the upper limit;&#xD;
&#xD;
          -  History or treatment for epilepsy;&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Flora MF Moreira, Graduate</last_name>
    <role>Study Chair</role>
    <affiliation>MsC Student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andrea SS Carbone, MsC</last_name>
    <role>Study Chair</role>
    <affiliation>PhD student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Flavia PC Sacchi, MsC</last_name>
    <role>Study Chair</role>
    <affiliation>PhD student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paulo CP Santos, Graduate</last_name>
    <role>Study Chair</role>
    <affiliation>MsC Student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rafaele CP Araújo, MsC</last_name>
    <role>Study Chair</role>
    <affiliation>PhD student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alessandra C Leite, MsC</last_name>
    <role>Study Chair</role>
    <affiliation>PhD student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cassia B Reis, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Pos doc Student</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Valeria C Rolla, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jason R Andrews, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roberto Oliveira</name>
      <address>
        <city>Dourados</city>
        <state>Mato Grosso Do Sul</state>
        <zip>78824210</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>http://www.prisonstudies.org/country/brazil</url>
    <description>World Prison Brief: Brazil.</description>
  </link>
  <link>
    <url>https://www.sealedenvelope.com/power/binary-superiority</url>
    <description>Power calculator for binary outcome superiority trial.</description>
  </link>
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    <citation>THOREN M, HINSHAW HC. Therapy of pulmonary tuberculosis with isoniazid alone and in combination with streptomycin and with para-amino-salicylic acid. Stanford Med Bull. 1952 Nov;10(4):316-8. No abstract available.</citation>
    <PMID>13015302</PMID>
  </reference>
  <reference>
    <citation>Urrego J, Ko AI, da Silva Santos Carbone A, Paiao DS, Sgarbi RV, Yeckel CW, Andrews JR, Croda J. The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in Brazilian Prisons. Am J Trop Med Hyg. 2015 Oct;93(4):739-46. doi: 10.4269/ajtmh.15-0166. Epub 2015 Jul 20.</citation>
    <PMID>26195459</PMID>
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    <citation>Vieira AA, Ribeiro SA, de Siqueira AM, Galesi VM, dos Santos LA, Golub JE. Prevalence of patients with respiratory symptoms through active case finding and diagnosis of pulmonary tuberculosis among prisoners and related predictors in a jail in the city of Carapicuiba, Brazil. Rev Bras Epidemiol. 2010 Dec;13(4):641-50. doi: 10.1590/s1415-790x2010000400009.</citation>
    <PMID>21180853</PMID>
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    <citation>Zumla A, George A, Sharma V, Herbert RH; Baroness Masham of Ilton; Oxley A, Oliver M. The WHO 2014 global tuberculosis report--further to go. Lancet Glob Health. 2015 Jan;3(1):e10-2. doi: 10.1016/S2214-109X(14)70361-4. No abstract available.</citation>
    <PMID>25539957</PMID>
  </reference>
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    <citation>Al-Darraji HA, Kamarulzaman A, Altice FL. Isoniazid preventive therapy in correctional facilities: a systematic review. Int J Tuberc Lung Dis. 2012 Jul;16(7):871-9. doi: 10.5588/ijtld.11.0447. Epub 2012 Mar 7.</citation>
    <PMID>22410101</PMID>
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    <citation>Barrera, L. The basics of clinical bacteriology Tuberculosis (2007): 93-112.</citation>
  </reference>
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    <citation>Daniel TM. The history of tuberculosis. Respir Med. 2006 Nov;100(11):1862-70. doi: 10.1016/j.rmed.2006.08.006. Epub 2006 Sep 1.</citation>
    <PMID>16949809</PMID>
  </reference>
  <reference>
    <citation>Porter JD, McAdam KP. The re-emergence of tuberculosis. Annu Rev Public Health. 1994;15:303-23. doi: 10.1146/annurev.pu.15.050194.001511.</citation>
    <PMID>8054087</PMID>
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    <citation>Nunn P, Williams B, Floyd K, Dye C, Elzinga G, Raviglione M. Tuberculosis control in the era of HIV. Nat Rev Immunol. 2005 Oct;5(10):819-26. doi: 10.1038/nri1704.</citation>
    <PMID>16200083</PMID>
  </reference>
  <reference>
    <citation>Schluger NW, Rom WN. The host immune response to tuberculosis. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):679-91. doi: 10.1164/ajrccm.157.3.9708002. No abstract available.</citation>
    <PMID>9517576</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <results_first_submitted>September 3, 2019</results_first_submitted>
  <results_first_submitted_qc>October 2, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 25, 2019</results_first_posted>
  <last_update_submitted>October 2, 2019</last_update_submitted>
  <last_update_submitted_qc>October 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Federal University of Mato Grosso</investigator_affiliation>
    <investigator_full_name>Roberto D Oliveira</investigator_full_name>
    <investigator_title>PhD Student</investigator_title>
  </responsible_party>
  <keyword>Tuberculosis</keyword>
  <keyword>Primary prevention</keyword>
  <keyword>Prisoners</keyword>
  <keyword>Controlled Clinical Trial</keyword>
  <keyword>Isoniazid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Tuberculosis, Pulmonary</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Isoniazid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03028129/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03028129/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Eligible participants were interviewed for eligibility criteria (age, race, alcohol use, comorbidities) and laboratory tests (HIV, hepatitis B and C, liver enzymes, interferon gamma dosing for tuberculosis antigens and active tuberculosis).</recruitment_details>
      <pre_assignment_details>Study was discontinued at ninth month after interim analysis and showed efficacy in intervention group less than 2.5%</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment</title>
          <description>Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Each subject received two weekly supervised oral doses of placebo, without the active ingredient, similar in size, weight, color, taste and odor.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="258"/>
                <participants group_id="P2" count="209"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="132"/>
                <participants group_id="P2" count="122"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="87"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="38"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received at least one dose of isoniazid or placebo.</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment</title>
          <description>Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="258"/>
            <count group_id="B2" value="209"/>
            <count group_id="B3" value="467"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.2" spread="6.7"/>
                    <measurement group_id="B2" value="29.0" spread="7.1"/>
                    <measurement group_id="B3" value="29.1" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="258"/>
                    <measurement group_id="B2" value="209"/>
                    <measurement group_id="B3" value="467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="130"/>
                    <measurement group_id="B2" value="109"/>
                    <measurement group_id="B3" value="239"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="105"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="195"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Brazil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="258"/>
                    <measurement group_id="B2" value="209"/>
                    <measurement group_id="B3" value="467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.</title>
        <description>Number of participants who had a Quantiferon TB Gold Plus (QIAGEN®) score greater than or equal to 0.35 international units per milliliter, at the time of the premature exclusion visit, on all participants in the group.</description>
        <time_frame>up to 6 months</time_frame>
        <population>All participants who received at least one dose of isoniazid or placebo and who had blood sample collected to QFT examination at premature exclusion visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment</title>
            <description>Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).</description>
          </group>
        </group_list>
        <measure>
          <title>Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.</title>
          <description>Number of participants who had a Quantiferon TB Gold Plus (QIAGEN®) score greater than or equal to 0.35 international units per milliliter, at the time of the premature exclusion visit, on all participants in the group.</description>
          <population>All participants who received at least one dose of isoniazid or placebo and who had blood sample collected to QFT examination at premature exclusion visit.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="132"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 months</time_frame>
      <desc>On the intervention days, all participants were asked about the presence of any unusual signs and / or symptoms. Data were recorded in a log containing start and end date, event description, degree and intervention performed.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment</title>
          <description>Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="258"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="209"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="258"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated SGOT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="258"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="190" subjects_at_risk="258"/>
                <counts group_id="E2" subjects_affected="109" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastric pain</sub_title>
                <counts group_id="E1" events="27" subjects_affected="27" subjects_at_risk="258"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="209"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="258"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="29" subjects_affected="29" subjects_at_risk="258"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Flu syndrome</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="258"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="27" subjects_affected="27" subjects_at_risk="258"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="209"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="30" subjects_affected="30" subjects_at_risk="258"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="258"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="21" subjects_affected="21" subjects_at_risk="258"/>
                <counts group_id="E2" events="24" subjects_affected="24" subjects_at_risk="209"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="258"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="209"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Loss to follow-up Interruption of the study Arms presented differential group allocation Statistical power to detect the primary endpoint was 73%, lower than estimated in our sample size calculation</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Julio Croda</name_or_title>
      <organization>Federal University of Mato Grosso do Sul</organization>
      <phone>+5567981229959</phone>
      <email>julio.croda@ufms.br</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03028129
org study id: U1111-1189-0829
nct id: NCT03028129
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to determine if the isoniazid is effective in the prevention of
      tuberculosis in a prison population, exposed to the high endemicity of the disease.
Despite being a known disease of mankind over 9000 years, tuberculosis (TB) is still a major
      public health problem in developing countries, mainly due to so-called highly endemic sites,
      such as prisons.

      It is Infectious disease, with airborne transmission, TB can present both the active or
      latent form. Despite the biological aspect of transmission, unhealthy environmental
      conditions (room without direct sunlight, poor ventilation and overcrowded) and individual
      factors (malnutrition, immunosuppression, use of alcohol and other drugs) have significant
      influence on transferability and infectivity.

      With the discovery of drugs active against Mycobacterium tuberculosis, it was observed a
      reduction of disease incidence in the world. Despite this declining incidence, World Health
      Organization (WHO) classifies TB as a public health problem due to the emergence of multidrug
      strains or extensively resistant to treatment, added to the cases of latent TB reactivation,
      observed with the advent of HIV/AIDS.

      Studies show a direct relationship between the incidence of TB and the prison environment.
      Nevertheless, the presence of prisons in one location increases the incidence of this
      disease, indicating that there is an exchange of disease between the prison and the
      community.

      Currently, control of TB in the prison system is based on the tracking of individuals with
      active TB and / or latent and, in their respective treatment. For the identification of
      individuals with active disease, it is necessary the recognition of respiratory symptoms
      (cough mainly) and sputum smear microscopy and sputum culture, and chest X-ray. As the search
      of individuals with latent form, must be carried to the skin test with Purified Protein
      Derived (PPD).

      Most of the units of the Brazilian's prison system these diagnostic methods are not available
      and hence the transport of individuals for their realization is necessary, generating an
      additional cost, in most cases, unfeasible process execution.

      With the completion of this study, it seek to determine the effectiveness of primary
      prophylaxis in the prison population in order to gather new scientific evidence, to bring
      affordable methods for the control of TB in prisons.

      Despite advances in diagnosis and treatment TB, this is the third leading cause of death from
      infectious diseases worldwide (Naghavi et al, 2015). In 2015, the WHO estimated incidence of
      9.6 million new cases of TB in the world, with about 1.1 million deaths. For Brazil it was
      estimated incidence of 44 cases per 100,000 (WHO, 2015). The incidence of TB has declined
      about 2% per year, but this rate is not homogeneous in the global context.

      Brazil occupies the 22nd place in the ranking of the WHO with an estimated annual rate of
      83,310 cases of the disease (Zumla et al, 2015). In the past seven years, it is estimated
      that the incidence declined only 0.7% (per year). A key factor in this slow progress in TB
      control in Brazil, and other emerging countries is the existence of high-risk subpopulations,
      including slums and prisons, which act as reservoirs and amplifiers for the transmission of
      the disease (Basu; Stückler; Mckee 2011; Dowdy et al, 2012). A recent systematic review
      showed that the average incidence of TB in the prison population can be up to 23 times that
      recorded in the general population (Baussano et al, 2010).

      With the fourth largest prison populations in the world, is observed in Brazil, the increased
      incidence of TB among prisoners in the last seven years. Although prisoners represent only
      0.3% of the population, the increase in the prison population over this period resulted in
      almost doubling the proportion of all TB cases that occur among prisoners (4.1% in 2007, 8,
      1% in 2013).

      The arrests are in an ideal environment for the spread of TB, since they show individuals
      users of tobacco and alcohol in high doses, in addition to drug abuse in overcrowded cells
      with poor ventilation and with limited access to care health and diagnosis of TB. Currently,
      the Ministry of Health recommends active search for TB at the entrance to the prison and once
      a year by chest X-ray. Due to the cost and logistics, most prisons do not adhere to this
      recommendation. There is also a clear recommendation not to use the tuberculin skin test or
      perform the treatment for latent tuberculosis. If the procedures for active case detection
      and / or prophylactic treatment would impact the high transmission in prisons is a question
      that still remains open (Al-Darraji; Kamarulzamn; Altice, 2012).

      The concentration of cases of TB in prisons can represent both an obstacle and an opportunity
      to control the disease, depending on the effectiveness of interventions in these
      environments.

      Preliminary studies show high annual rate of TB infection (26%) among the prison population
      of 12 penitentiaries of Mato Grosso do Sul. Besides the large burden of disease in this
      population is significant dispersion of the TB prison to the community (Sacchi et al, 2015).
      Cross-sectional studies show high yield annual screening for TB, however, the effectiveness
      of this measure combined with other interventions remains unclear (Ferreira et al, 1996;
      Fournet et al, 2006; Lemos et al, 2014; Vieira et al, 2010; Sanches et al, 2013; Walnut;
      Abrahão; Galesi, 2012; Kuhleis et al, 2012; Estevan; Oliveira; Croda, 2013). Due to the
      combination of high force of infection in prisons and short prison term, primary prophylaxis
      may be an effective intervention. This new approach has never been evaluated in the context
      of prisons in low and middle income countries; to assess the impact of program strategies for
      TB screening and prophylaxis, longitudinal data will be essential. Given the infrastructure
      that was created for long-term prospective studies in Brazil, there is an excellent
      opportunity to close the critical knowledge gaps that have been barriers to effective
      implementation of TB control in high transmission prisons.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Quantiferon TB Gold Plus (QIAGEN®) Conversion at the Premature Exclusion Visit.
time frame: up to 6 months
description: Number of participants who had a Quantiferon TB Gold Plus (QIAGEN®) score greater than or equal to 0.35 international units per milliliter, at the time of the premature exclusion visit, on all participants in the group.
arm group label: Treatment
arm group type: Experimental
description: Each subject received two oral supervised weekly doses of isoniazid 900 milligrams.
arm group label: Control
arm group type: Placebo Comparator
description: Each subject received two oral supervised weekly doses of placebo (oral tablet, without the active ingredient, similar in size, weight, color, taste and odor).
intervention type: Drug
intervention name: Isoniazid 900 milligrams
description: Oral tablet, with the isoniazid 900mg, given two weekly. The administration will be supervised.
arm group label: Treatment
other name: Antibiotic Treatment
intervention type: Drug
intervention name: Placebo
description: Oral tablet, without the active ingredient, similar in size, weight, color, taste and odor.
arm group label: Control
other name: Placebo Treatment
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Flora MF Moreira, Graduate
role: Study Chair
affiliation: MsC Student
last name: Andrea SS Carbone, MsC
role: Study Chair
affiliation: PhD student
last name: Flavia PC Sacchi, MsC
role: Study Chair
affiliation: PhD student
last name: Paulo CP Santos, Graduate
role: Study Chair
affiliation: MsC Student
last name: Rafaele CP Araújo, MsC
role: Study Chair
affiliation: PhD student
last name: Alessandra C Leite, MsC
role: Study Chair
affiliation: PhD student
last name: Cassia B Reis, PhD
role: Study Chair
affiliation: Pos doc Student
last name: Valeria C Rolla, PhD
role: Study Chair
affiliation: Professor
last name: Jason R Andrews, PhD
role: Study Chair
affiliation: Professor
facility: 
country: Brazil
url: http://www.prisonstudies.org/country/brazil
description: World Prison Brief: Brazil.
url: https://www.sealedenvelope.com/power/binary-superiority
description: Power calculator for binary outcome superiority trial.
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responsible party type: Principal Investigator
investigator affiliation: Federal University of Mato Grosso
investigator full name: Roberto D Oliveira
investigator title: PhD Student
mesh term: Tuberculosis
mesh term: Tuberculosis, Pulmonary
mesh term: Anti-Bacterial Agents
mesh term: Isoniazid
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Loss to follow-up Interruption of the study Arms presented differential group allocation Statistical power to detect the primary endpoint was 73%, lower than estimated in our sample size calculation
point of contact: 