<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/NCT03245398</url>
  </required_header>
  <id_info>
    <org_study_id>TRIPLEMEB_PEMBA</org_study_id>
    <nct_id>NCT03245398</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of a Multi-dose Regimen of Mebendazole Against Hookworm in Children</brief_title>
  <official_title>Efficacy and Safety of a Single-dose Regimen and a Multi-dose Regimen of Mebendazole Against Hookworm Infections in School Children: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jennifer Keiser</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PATH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Public Health Laboratory Ivo de Carneri</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Swiss Tropical &amp; Public Health Institute</source>
  <oversight_info>
    <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>
      This study is a double-blind randomized clinical trial which aims at providing evidence on&#xD;
      the efficacy and safety of two regimens of mebendazole in school-aged children. Thus, our&#xD;
      primary objective is to assess the efficacy and safety of: i) 100 mg solid tablets twice a&#xD;
      day for 3 days, and ii) one dose of 500 mg solid tablets of mebendazole in participants aged&#xD;
      6-12, inclusive, infected with hookworm.&#xD;
&#xD;
      The primary endpoint of the trial is the cure rate (CR) of the 3-day regimen of mebendazole&#xD;
      against hookworm and a single dose mebendazole treatment.&#xD;
&#xD;
      The secondary objectives are to determine if the multi-dose regimen is superior to the single&#xD;
      dose regimen, evaluate the efficacy against concomitant soil-transmitted helminth infections,&#xD;
      and assess the safety of both mebendazole regimens.&#xD;
&#xD;
      After obtaining informed consent from children's caregiver, the medical history of the&#xD;
      participating individuals will be assessed with a standardized questionnaire, in addition to&#xD;
      a clinical examination carried out by the study physician on the treatment day. Enrollment&#xD;
      will be based on two stool samples which will be collected, if possible, on two consecutive&#xD;
      days or otherwise within a maximum of 5 days apart. All stool samples will be examined with&#xD;
      duplicated Kato-Katz thick smears by experienced laboratory technicians.&#xD;
&#xD;
      Randomization of participants into the two treatment arms will be stratified according to&#xD;
      intensity of infection. Participants will be interviewed before treatment for clinical&#xD;
      symptoms and 3 hours after every morning treatment and 24 hours after every morning treatment&#xD;
      about the occurrence of adverse events. The efficacy of the treatment will be determined&#xD;
      14-21 days post-treatment by collecting another two stool samples.&#xD;
&#xD;
      The primary analysis will include all participants with primary end point data (available&#xD;
      case analysis). Supplementary, two sensitivity analyses will be conducted imputing all&#xD;
      missing endpoint data as treatment failures or all as treatment success. CRs will be&#xD;
      calculated as the percentage of egg-positive participants at baseline who become egg-negative&#xD;
      after treatment. CRs will be compared by using unadjusted logistic regression. To assess&#xD;
      model robustness with respect to covariates, adjusted logistic regressions (adjustment for&#xD;
      age, sex, school, weight and strata) will be performed.&#xD;
&#xD;
      Geometric and arithmetic mean egg counts will be calculated for the different treatment arms&#xD;
      before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with&#xD;
      5,000 replicates will be used to calculate 95% confidence intervals (CIs) for ERRs and the&#xD;
      difference of the ERRs.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 25, 2017</start_date>
  <completion_date type="Actual">September 15, 2017</completion_date>
  <primary_completion_date type="Actual">September 15, 2017</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Participants, physicians, nurses and investigators will all be blinded. Based on the randomization list, individual envelopes with the correct combination of mebendazole tablets and placebos will be prepared. The randomization code is then sealed in an envelope. Unblinding will only occur in case of a SAE, SUSAR or other kind of emergency.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cure Rate (CR) of Mebendazole Against Hookworm</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens of Mebendazole Against Hookworm</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CR of Both Mebendazole Regimens Against Trichuris Trichiura</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric ERR of Both Mebendazole Regimens Against Trichuris Trichiura</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides.</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arithmetic ERR of the Two Regimens of Mebendazole Against Hookworm</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arithmetic ERR of Both Mebendazole Regimens Against Trichuris Trichiura</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arithmetic ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides</measure>
    <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
    <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Comparison of the Sensitivity of Kato Katz to Quantitative Polymerase Chain Reaction (PCR) Assays</measure>
    <time_frame>1 year</time_frame>
    <description>Two aliquots (about 1 g of stool each) of positive samples will be stored in ethanol and transported to the Swiss Tropical Public Health Institute for subsequent DNA extraction and diagnostic.</description>
  </other_outcome>
  <other_outcome>
    <measure>Prevalence of Genetic Resistance Markers Among Participants</measure>
    <time_frame>2 years</time_frame>
    <description>The same two aliquots of stool will be used in this section.. Additionally, a Harada Mori culture will be prepared from one of the stool samples of each child at baseline and at follow-up to extract hatched larvae. Larvae will be stored in ethanol. Both stool and larvae samples will undergo an assessment of drug resistance-associated single-nucleotide polymorphisms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Distribution of Hookworm Species Among Participants</measure>
    <time_frame>1 year</time_frame>
    <description>Genetic differentiation between Necator americanus and Ancylostoma duodenale using PCRs will allow us to identify which of the species is most prevalent.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">186</enrollment>
  <condition>Hookworm</condition>
  <arm_group>
    <arm_group_label>Single dose of mebendazole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In day 1 each child in this treatment arm will receive a 500 mg tablet of mebendazole plus one 100 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the placebo. In day 2 and 3 each child will receive one placebo twice a day (in the morning and in the evening)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple dose of mebendazole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In day 1 each child in this treatment arm will receive a 100 mg tablet of mebendazole plus one 500 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the 100 mg tablet of mebendazole. In day 2 and 3 each child will receive one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment with one of the two regimens of mebendazole</intervention_name>
    <description>Once in the morning and once in the evening for 3 consecutive days</description>
    <arm_group_label>Multiple dose of mebendazole</arm_group_label>
    <arm_group_label>Single dose of mebendazole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent signed by parents and/or caregiver; and oral assent by&#xD;
             participant.&#xD;
&#xD;
          -  Able and willing to be examined by a study physician at the beginning of the study.&#xD;
&#xD;
          -  Able and willing to provide two stool samples at the beginning (baseline) and&#xD;
             approximately three weeks after treatment (follow-up).&#xD;
&#xD;
          -  Positive for hookworm eggs in the stool (≥ 100 EPG and at least two Kato-Katz thick&#xD;
             smears slides with more than one hookworm egg).&#xD;
&#xD;
          -  Absence of major systemic illnesses, e.g. diabetes, severe anemia (HB&lt;8.0 g/l) as&#xD;
             assessed by a medical doctor at school, upon initial clinical assessment.&#xD;
&#xD;
          -  No known or reported history of chronical illness as cancer, diabetes, chronic heart,&#xD;
             liver or renal disease.&#xD;
&#xD;
          -  No recent anthelminthic treatment (within past 4 weeks). No known allergy to study&#xD;
             medications (mebendazole and albendazole).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        No written informed consent by parents and/or caregiver; no oral assent by participant.&#xD;
&#xD;
          -  Menarche, based on self-report&#xD;
&#xD;
          -  Presence of major systemic illnesses, e.g. diabetes, severe anemia (HB&lt;8.0 g/l) as&#xD;
             assessed by a medical doctor, upon initial clinical assessment.&#xD;
&#xD;
          -  History of acute or severe chronic disease.&#xD;
&#xD;
          -  Recent use of anthelminthic drug (within past 4 weeks).&#xD;
&#xD;
          -  Attending other clinical trials during the study.&#xD;
&#xD;
          -  Negative diagnostic result for hookworm eggs in the stool (&lt; 100 EPG (total of the&#xD;
             four slides) and/or only one Kato-Katz thick smear slide with more than one hookworm&#xD;
             egg).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer Keiser, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Swiss Tropical &amp; Public Health Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Public Health Laboratory Ivo de Carneri, P.O. Box 122</name>
      <address>
        <city>Chake Chake</city>
        <state>Pemba</state>
        <country>Tanzania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Tanzania</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>July 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <results_first_submitted>November 21, 2018</results_first_submitted>
  <results_first_submitted_qc>March 14, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 17, 2019</results_first_posted>
  <last_update_submitted>March 14, 2019</last_update_submitted>
  <last_update_submitted_qc>March 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Swiss Tropical &amp; Public Health Institute</investigator_affiliation>
    <investigator_full_name>Jennifer Keiser</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hookworm Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mebendazole</mesh_term>
    <mesh_term>Piperazine</mesh_term>
    <mesh_term>Piperazine citrate</mesh_term>
    <mesh_term>DMP 777</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03245398/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Single 500 mg Dose of Mebendazole</title>
          <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
        </group>
        <group group_id="P2">
          <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
          <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="93"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="92"/>
                <participants group_id="P2" count="93"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Travelled to another island</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Single 500 mg Dose of Mebendazole</title>
          <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
        </group>
        <group group_id="B2">
          <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
          <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</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="93"/>
            <count group_id="B2" value="93"/>
            <count group_id="B3" value="186"/>
          </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="10.1" spread="1.6"/>
                    <measurement group_id="B2" value="10.1" spread="1.6"/>
                    <measurement group_id="B3" value="10.1" spread="1.6"/>
                  </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="39"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="93"/>
                    <measurement group_id="B3" value="186"/>
                  </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>Tanzania</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="93"/>
                    <measurement group_id="B3" value="186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean weight (kg)</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.7" spread="5.3"/>
                    <measurement group_id="B2" value="26.2" spread="5.1"/>
                    <measurement group_id="B3" value="26.4" spread="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean height (cm)</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="132.0" spread="10.2"/>
                    <measurement group_id="B2" value="131.8" spread="9.6"/>
                    <measurement group_id="B3" value="131.9" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Infected with hookworm</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="93"/>
                    <measurement group_id="B3" value="186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Median EPG hookworm</title>
          <units>Eggs per gram (EPG)</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="222" lower_limit="78" upper_limit="534"/>
                    <measurement group_id="B2" value="222" lower_limit="96" upper_limit="606"/>
                    <measurement group_id="B3" value="222" lower_limit="90" upper_limit="582"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EPG hookworm (geometric mean)</title>
          <units>EPG</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="219" lower_limit="172" upper_limit="279"/>
                    <measurement group_id="B2" value="234" lower_limit="185" upper_limit="297"/>
                    <measurement group_id="B3" value="226" lower_limit="191" upper_limit="268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Light hookworm infection (1-1999 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="179"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Moderate hookworm infection (2000-3999 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Heavy hookworm infection (≥4000 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Infected with T. trichiura</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="88"/>
                    <measurement group_id="B2" value="91"/>
                    <measurement group_id="B3" value="179"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EPG T. trichiura (geometric mean)</title>
          <units>EPG</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="661.8" lower_limit="541" upper_limit="809"/>
                    <measurement group_id="B2" value="725.7" lower_limit="574" upper_limit="918"/>
                    <measurement group_id="B3" value="693" lower_limit="595" upper_limit="808"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Light T. trichiura infection (1-999 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="115"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Moderate T. trichiura infection (1000-9999 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Heavy T. trichiura infection (≥10,000 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <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>Infected with A. lumbricoides</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EPG A. lumbricoides (geometric mean)</title>
          <units>EPG</units>
          <param>Geometric Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2691.2" lower_limit="1379" upper_limit="5251"/>
                    <measurement group_id="B2" value="4095.9" lower_limit="2233" upper_limit="7513"/>
                    <measurement group_id="B3" value="3349" lower_limit="2148" upper_limit="5219"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Light A. lumbricoides infection (1-4999 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Moderate A. lumbricoides infection (5000-49,999 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Heavy A. lumbricoides infection (≥50,000 EPG)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cure Rate (CR) of Mebendazole Against Hookworm</title>
        <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Cure Rate (CR) of Mebendazole Against Hookworm</title>
          <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
          <units>percentage of participants cured</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13" lower_limit="6.9" upper_limit="21.7"/>
                    <measurement group_id="O2" value="97.9" lower_limit="92.4" upper_limit="99.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens of Mebendazole Against Hookworm</title>
        <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens of Mebendazole Against Hookworm</title>
          <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
          <units>percentage change</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-68.0" lower_limit="-78.6" upper_limit="-51.5"/>
                    <measurement group_id="O2" value="-100" lower_limit="-100" upper_limit="-99.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CR of Both Mebendazole Regimens Against Trichuris Trichiura</title>
        <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>CR of Both Mebendazole Regimens Against Trichuris Trichiura</title>
          <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
          <units>percentage of participants cured</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" lower_limit="4.6" upper_limit="17.8"/>
                    <measurement group_id="O2" value="42.9" lower_limit="33.8" upper_limit="54.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Geometric ERR of Both Mebendazole Regimens Against Trichuris Trichiura</title>
        <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric ERR of Both Mebendazole Regimens Against Trichuris Trichiura</title>
          <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
          <units>percentage of change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-71.7" lower_limit="-78.5" upper_limit="-56.7"/>
                    <measurement group_id="O2" value="-98.1" lower_limit="-98.7" upper_limit="-96.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides</title>
        <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides</title>
          <description>Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.</description>
          <units>percentage of participants cured</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="100" upper_limit="100"/>
                    <measurement group_id="O2" value="98" lower_limit="94.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Geometric ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides.</title>
        <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Geometric ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides.</title>
          <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-100" lower_limit="-100" upper_limit="-100"/>
                    <measurement group_id="O2" value="-100" lower_limit="-100" upper_limit="-100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Arithmetic ERR of the Two Regimens of Mebendazole Against Hookworm</title>
        <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Dose of Mebendazole</title>
            <description>In day 1 each child in this treatment arm will receive a 500 mg tablet of mebendazole plus one 100 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the placebo. In day 2 and 3 each child will receive one placebo twice a day (in the morning and in the evening)&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple Dose of Mebendazole</title>
            <description>In day 1 each child in this treatment arm will receive a 100 mg tablet of mebendazole plus one 500 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the 100 mg tablet of mebendazole. In day 2 and 3 each child will receive one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Arithmetic ERR of the Two Regimens of Mebendazole Against Hookworm</title>
          <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-52.7" lower_limit="-63.6" upper_limit="-40.3"/>
                    <measurement group_id="O2" value="-99.8" lower_limit="-100" upper_limit="-99.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Arithmetic ERR of Both Mebendazole Regimens Against Trichuris Trichiura</title>
        <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Arithmetic ERR of Both Mebendazole Regimens Against Trichuris Trichiura</title>
          <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-49.1" lower_limit="-61.0" upper_limit="-31.7"/>
                    <measurement group_id="O2" value="-91.6" lower_limit="-94.6" upper_limit="-88.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Arithmetic ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides</title>
        <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
        <time_frame>baseline (before treatment) and 18 to 22 days post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single 500 mg Dose of Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
          <group group_id="O2">
            <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
            <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
          </group>
        </group_list>
        <measure>
          <title>Arithmetic ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides</title>
          <description>Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the &quot;outcome measure&quot; entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-100" lower_limit="-100" upper_limit="-100"/>
                    <measurement group_id="O2" value="-99.1" lower_limit="-100" upper_limit="-96.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Comparison of the Sensitivity of Kato Katz to Quantitative Polymerase Chain Reaction (PCR) Assays</title>
        <description>Two aliquots (about 1 g of stool each) of positive samples will be stored in ethanol and transported to the Swiss Tropical Public Health Institute for subsequent DNA extraction and diagnostic.</description>
        <time_frame>1 year</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Prevalence of Genetic Resistance Markers Among Participants</title>
        <description>The same two aliquots of stool will be used in this section.. Additionally, a Harada Mori culture will be prepared from one of the stool samples of each child at baseline and at follow-up to extract hatched larvae. Larvae will be stored in ethanol. Both stool and larvae samples will undergo an assessment of drug resistance-associated single-nucleotide polymorphisms.</description>
        <time_frame>2 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Distribution of Hookworm Species Among Participants</title>
        <description>Genetic differentiation between Necator americanus and Ancylostoma duodenale using PCRs will allow us to identify which of the species is most prevalent.</description>
        <time_frame>1 year</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data collected 3h after the first treatment time point</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Single 500 mg Dose of Mebendazole</title>
          <description>In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
        </group>
        <group group_id="E2">
          <title>Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole</title>
          <description>In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).&#xD;
Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days</description>
        </group>
      </group_list>
      <serious_events>
        <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="93"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="93"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="2" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="93"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="93"/>
              </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>
    <point_of_contact>
      <name_or_title>Dr Jennifer Keiser</name_or_title>
      <organization>Swiss Tropical and Public Health Institute</organization>
      <phone>+41 61 284 8218</phone>
      <email>jennifer.keiser@swisstph.ch</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/NCT03245398
org study id: TRIPLEMEB_PEMBA
nct id: NCT03245398
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study is a double-blind randomized clinical trial which aims at providing evidence on
      the efficacy and safety of two regimens of mebendazole in school-aged children. Thus, our
      primary objective is to assess the efficacy and safety of: i) 100 mg solid tablets twice a
      day for 3 days, and ii) one dose of 500 mg solid tablets of mebendazole in participants aged
      6-12, inclusive, infected with hookworm.

      The primary endpoint of the trial is the cure rate (CR) of the 3-day regimen of mebendazole
      against hookworm and a single dose mebendazole treatment.

      The secondary objectives are to determine if the multi-dose regimen is superior to the single
      dose regimen, evaluate the efficacy against concomitant soil-transmitted helminth infections,
      and assess the safety of both mebendazole regimens.

      After obtaining informed consent from children's caregiver, the medical history of the
      participating individuals will be assessed with a standardized questionnaire, in addition to
      a clinical examination carried out by the study physician on the treatment day. Enrollment
      will be based on two stool samples which will be collected, if possible, on two consecutive
      days or otherwise within a maximum of 5 days apart. All stool samples will be examined with
      duplicated Kato-Katz thick smears by experienced laboratory technicians.

      Randomization of participants into the two treatment arms will be stratified according to
      intensity of infection. Participants will be interviewed before treatment for clinical
      symptoms and 3 hours after every morning treatment and 24 hours after every morning treatment
      about the occurrence of adverse events. The efficacy of the treatment will be determined
      14-21 days post-treatment by collecting another two stool samples.

      The primary analysis will include all participants with primary end point data (available
      case analysis). Supplementary, two sensitivity analyses will be conducted imputing all
      missing endpoint data as treatment failures or all as treatment success. CRs will be
      calculated as the percentage of egg-positive participants at baseline who become egg-negative
      after treatment. CRs will be compared by using unadjusted logistic regression. To assess
      model robustness with respect to covariates, adjusted logistic regressions (adjustment for
      age, sex, school, weight and strata) will be performed.

      Geometric and arithmetic mean egg counts will be calculated for the different treatment arms
      before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with
      5,000 replicates will be used to calculate 95% confidence intervals (CIs) for ERRs and the
      difference of the ERRs.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Participants, physicians, nurses and investigators will all be blinded. Based on the randomization list, individual envelopes with the correct combination of mebendazole tablets and placebos will be prepared. The randomization code is then sealed in an envelope. Unblinding will only occur in case of a SAE, SUSAR or other kind of emergency.
measure: Cure Rate (CR) of Mebendazole Against Hookworm
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
measure: Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens of Mebendazole Against Hookworm
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).
measure: CR of Both Mebendazole Regimens Against Trichuris Trichiura
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
measure: Geometric ERR of Both Mebendazole Regimens Against Trichuris Trichiura
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).
measure: Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
measure: Geometric ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides.
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).
measure: Arithmetic ERR of the Two Regimens of Mebendazole Against Hookworm
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).
measure: Arithmetic ERR of Both Mebendazole Regimens Against Trichuris Trichiura
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).
measure: Arithmetic ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides
time frame: baseline (before treatment) and 18 to 22 days post-treatment
description: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).
measure: Comparison of the Sensitivity of Kato Katz to Quantitative Polymerase Chain Reaction (PCR) Assays
time frame: 1 year
description: Two aliquots (about 1 g of stool each) of positive samples will be stored in ethanol and transported to the Swiss Tropical Public Health Institute for subsequent DNA extraction and diagnostic.
measure: Prevalence of Genetic Resistance Markers Among Participants
time frame: 2 years
description: The same two aliquots of stool will be used in this section.. Additionally, a Harada Mori culture will be prepared from one of the stool samples of each child at baseline and at follow-up to extract hatched larvae. Larvae will be stored in ethanol. Both stool and larvae samples will undergo an assessment of drug resistance-associated single-nucleotide polymorphisms.
measure: Distribution of Hookworm Species Among Participants
time frame: 1 year
description: Genetic differentiation between Necator americanus and Ancylostoma duodenale using PCRs will allow us to identify which of the species is most prevalent.
arm group label: Single dose of mebendazole
arm group type: Active Comparator
description: In day 1 each child in this treatment arm will receive a 500 mg tablet of mebendazole plus one 100 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the placebo. In day 2 and 3 each child will receive one placebo twice a day (in the morning and in the evening)
arm group label: Multiple dose of mebendazole
arm group type: Active Comparator
description: In day 1 each child in this treatment arm will receive a 100 mg tablet of mebendazole plus one 500 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the 100 mg tablet of mebendazole. In day 2 and 3 each child will receive one 100 mg tablet of mebendazole twice a day (in the morning and in the evening).
intervention type: Drug
intervention name: Treatment with one of the two regimens of mebendazole
description: Once in the morning and once in the evening for 3 consecutive days
arm group label: Multiple dose of mebendazole
arm group label: Single dose of mebendazole
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: No
last name: Jennifer Keiser, PhD
role: Principal Investigator
affiliation: Swiss Tropical & Public Health Institute
facility: 
country: Tanzania
responsible party type: Sponsor-Investigator
investigator affiliation: Swiss Tropical & Public Health Institute
investigator full name: Jennifer Keiser
investigator title: Dr.
mesh term: Hookworm Infections
mesh term: Mebendazole
mesh term: Piperazine
mesh term: Piperazine citrate
mesh term: DMP 777
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 