xml: <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/NCT06037876</url>
    </required_header>
    <id_info>
      <org_study_id>BRCCH PII 2021</org_study_id>
      <nct_id>NCT06037876</nct_id>
    </id_info>
    <brief_title>Efficacy of Ivermectin-albendazole vs Albendazole Alone in School-aged Children Infected With Trichuris Trichiura</brief_title>
    <acronym>FACEITeffic</acronym>
    <official_title>Efficacy of the Combination Ivermectin and Albendazole vs Albendazole Alone in School-aged Children Infected With Trichuris Trichiura: a Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Jennifer Keiser</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Vector Borne &amp; Neglected Tropical Disease Control Division, Ministry of Health, Uganda</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Swiss Tropical &amp; Public Health Institute</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this parallel open-label randomized controlled superiority trial is to&#xD;
        demonstrate that co-administered ivermectin (200 µg/kg) plus albendazole (400 mg) is superior&#xD;
        to albendazole (400 mg) monotherapy in terms of cure rates against Trichuris trichiura&#xD;
        infections assessed by Kato-Katz at 14-21 days post-treatment in individuals aged 6-12 years.&#xD;
  &#xD;
        The main questions it aims to answer are:&#xD;
  &#xD;
          -  Is single oral dose combined ivermectin-albendazole superior to albendazole alone in&#xD;
             terms of cure rates and egg reduction rates against T. trichiura infections in children&#xD;
             aged 6-12 years in Uganda?&#xD;
  &#xD;
          -  Is single oral dose combined ivermectin-albendazole superior to albendazole alone in&#xD;
             terms of cure rates and egg reduction rates against co-infecting soil-transmitted&#xD;
             helminth infections such as Ascaris lumbricoides and hookworm in children aged 6-12&#xD;
             years in Uganda?&#xD;
  &#xD;
          -  Is single oral dose combined ivermectin-albendazole as tolerable and safe as albendazole&#xD;
             monotherapy in children aged 6-12 years in Uganda?&#xD;
  &#xD;
        Participants will be asked to provide two stool samples at baseline that will be subjected to&#xD;
        microscopic analysis using the Kato-Katz thick smear technique for detection of&#xD;
        soil-transmitted helminth eggs. T. trichiura-infected participants will be:&#xD;
  &#xD;
          -  clinically examined for general health, anthropometric parameters including height and&#xD;
             weight as well as temperature&#xD;
  &#xD;
          -  randomly assigned to either receive one single oral dose of combined ivermectin and&#xD;
             albendazole or albendazole monotherapy&#xD;
  &#xD;
          -  checked for any potential adverse events and will undergo a brief questionnaire on&#xD;
             specific symptoms 3h after drug administration&#xD;
  &#xD;
          -  asked to provide another two stool samples to be microscopically examined for helminth&#xD;
             eggs 14-21 days post-treatment Researchers will compare individuals treated with&#xD;
             ivermectin-albendazole and albendazole alone to see if the proportion of T. trichiura&#xD;
             egg-negative individuals and/or reduction in egg counts differs between these two groups&#xD;
             14-21 days after treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In view that efficacy of co-administered ivermectin (IVM) and albendazole (ALB) has been&#xD;
        found to vary between different settings the rationale of this parallel open-label randomized&#xD;
        controlled superiority trial is to provide evidence on the efficacy of co-administered&#xD;
        ivermectin and albendazole compared to albendazole monotherapy in school-aged children aged&#xD;
        6-12 years against infection with T. trichiura in Uganda.&#xD;
  &#xD;
        Our primary objective is to demonstrate superiority of&#xD;
  &#xD;
          1. Arm A: single dose of ivermectin (200 µg/kg, 3 mg tablets according to weight) / single&#xD;
             dose of albendazole (400 mg tablet) combination, compared to&#xD;
  &#xD;
          2. Arm B: single dose of albendazole (400 mg tablet)&#xD;
  &#xD;
        in terms of cure rate (CR) against T. trichiura infections in school-aged children aged 6-12&#xD;
        years assessed at 14-21 days post-treatment by Kato-Katz microscopy.&#xD;
  &#xD;
        The secondary objectives of the trial are:&#xD;
  &#xD;
          1. to determine the egg reduction rates (ERRs) of ivermectin/albendazole combination&#xD;
             therapy compared to albendazole monotherapy against T. trichiura&#xD;
  &#xD;
          2. to determine the CRs and ERRs of the study drugs against Ascaris lumbricoides and&#xD;
             hookworm in co-infected participants&#xD;
  &#xD;
          3. to evaluate the safety and tolerability of the treatment&#xD;
  &#xD;
        The study will be implemented as a school-based study and children aged 6-12 years from two&#xD;
        primary schools in Kabale district, southwestern Uganda will be invited for parasitological&#xD;
        examination after obtaining informed consent from parents/caregivers and assent by the minor&#xD;
        participants. Two stool samples will be collected, when possible, on two consecutive days.&#xD;
        Children found to be infected with T. trichiura based on quadruplicate Kato-Katz thick smear&#xD;
        readings will be enrolled into the actual trial. The medical history of the participants will&#xD;
        be assessed with a standardized questionnaire, in addition to a clinical examination carried&#xD;
        out by the study nurse/physician before treatment.&#xD;
  &#xD;
        All participants will be interviewed before treatment and after 3 and 24 hours (active&#xD;
        surveillance) for the occurrence of adverse events (AEs). Participants and their caregivers&#xD;
        will be told that any potential AEs happening between 24 hours and the respective follow-up&#xD;
        time point for stool collection should be reported to the local village health team (VHT)&#xD;
        members, which will be trained to handle the situation by taking the participant to a health&#xD;
        facility for timely treatment, or to local health workers directly.&#xD;
  &#xD;
        The efficacy of the treatment will be determined at 14-21 days post-treatment by collecting&#xD;
        another two stool samples.&#xD;
  &#xD;
        At both, baseline and follow-up (14-21 days post treatment) a portion of stool (1.5-2 g) from&#xD;
        all participants identified with T. trichiura infections will be preserved in 95% ethanol,&#xD;
        shipped to a reference laboratory in Switzerland and subjected to amplicon deep sequencing&#xD;
        for characterization of T. trichiura strains and investigation of potential resistance&#xD;
        markers.&#xD;
  &#xD;
        Study participants eligible for treatment will be randomly assigned to one of the two&#xD;
        treatment arms stratified by 2 levels of baseline infection intensity (light: 1-999 EPG, and&#xD;
        moderate plus heavy: ≥ 1000 EPG T. trichiura infections).&#xD;
  &#xD;
        The primary analysis will include all participants with primary end point data (available&#xD;
        case analysis). Supplementary, a per-protocol analysis will be conducted. CRs will be&#xD;
        calculated as the percentage of egg-positive subjects at baseline who become egg-negative&#xD;
        after treatment. Differences among CRs (between treatment arms) will be analyzed by using&#xD;
        crude and adjusted logistic regression modeling.&#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 differences in&#xD;
        ERRs.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 2023</completion_date>
    <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Parallel open-label randomized controlled superiority trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Allocation concealment will be warranted using sequential, opaque, sealed envelopes. Outcome assessors in the lab will be blinded.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Number of Participants T. Trichiura Egg Negative Post-Treatment (Cured)</measure>
      <time_frame>14-21 days after treatment</time_frame>
      <description>The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Egg Reduction Rate (ERR) against T. Trichiura</measure>
      <time_frame>14-21 days after 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. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants With Concomitant Soil-transmitted Helminth Infections Egg Negative Post-Treatment (Cured)</measure>
      <time_frame>14-21 days after treatment</time_frame>
      <description>Number of participants that converted from egg positive with Ascaris lumbricoides and/or hookworm infections to egg negative after 14-21 days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Egg-reduction Rates (ERRs) Against Concomitant Soil-transmitted Helminth Infections</measure>
      <time_frame>14-21 days after treatment</time_frame>
      <description>Percent change in geometric mean eggs per gram of stool from before to after treatment. ERRs will be calculated for Ascaris lumbricoides and hookworm infections as described in outcome 2.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Trichuriasis</condition>
    <arm_group>
      <arm_group_label>IVM (200 µg/kg) + ALB (400 mg)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A single tablet of albendazole (400mg) plus 200 µg/kg of ivermectin, provided as single oral dose.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>ALB (400mg)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>A single tablet of albendazole (400mg), provided as single oral dose.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>IVM (200 µg/kg) + ALB (400 mg)</intervention_name>
      <description>World Health Organization Pre-Qualification (WHO PQ) recommended ivermectin 3mg tablets will be used together with albendazole 400mg tablets as provided by WHO for Neglected Tropical Disease (NTD) programs.</description>
      <arm_group_label>IVM (200 µg/kg) + ALB (400 mg)</arm_group_label>
      <other_name>Zentel® and Stromectol®, Ivermectin Tablet 3mg</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ALB (400mg)</intervention_name>
      <description>Albendazole 400mg manufactured and donated by GlaxoSmithKline (GSK) to WHO</description>
      <arm_group_label>ALB (400mg)</arm_group_label>
      <other_name>Zentel®</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Written informed consent for participation signed from caregivers; and written assent&#xD;
               by participants.&#xD;
  &#xD;
            -  Agree to comply with study procedures, including provision of two stool samples at the&#xD;
               beginning (baseline) and at follow-up assessment 14-21 days after treatment.&#xD;
  &#xD;
            -  Willing to be examined by a study nurse/physician prior to treatment.&#xD;
  &#xD;
            -  At least two slides of the quadruple Kato-Katz thick smears positive for T. trichiura.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence or signs of major systemic illnesses, e.g. body temperature ≥ 38°C, clinical&#xD;
               malaria (fever + positive RDT) upon initial clinical assessment.&#xD;
  &#xD;
            -  Recent use of anthelmintic drug (within past 4 weeks).&#xD;
  &#xD;
            -  Attending other experimental research studies.&#xD;
  &#xD;
            -  Known allergy to study medications (i.e. benzimidazole or ivermectin).&#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_contact>
      <last_name>Jennifer Keiser, Prof</last_name>
      <phone>+41612848218</phone>
      <email>jennifer.keiser@swisstph.ch</email>
    </overall_contact>
    <location>
      <facility>
        <name>Vector Borne &amp; Neglected Tropical Disease Control Division, Ministry of Health</name>
        <address>
          <city>Kampala</city>
          <zip>P.O.Box 1661</zip>
          <country>Uganda</country>
        </address>
      </facility>
      <contact>
        <last_name>Prudence Beinamaryo</last_name>
        <phone>+256-789-548-930</phone>
        <email>prudenceb13@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Uganda</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</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>Prof. Dr.</investigator_title>
    </responsible_party>
    <keyword>Soil-transmitted helminths, Trichuris trichiura</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Trichuriasis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ivermectin</mesh_term>
      <mesh_term>Albendazole</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06037876
  org study id: BRCCH PII 2021
  nct id: NCT06037876
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this parallel open-label randomized controlled superiority trial is to
        demonstrate that co-administered ivermectin (200 µg/kg) plus albendazole (400 mg) is superior
        to albendazole (400 mg) monotherapy in terms of cure rates against Trichuris trichiura
        infections assessed by Kato-Katz at 14-21 days post-treatment in individuals aged 6-12 years.
  
        The main questions it aims to answer are:
  
          -  Is single oral dose combined ivermectin-albendazole superior to albendazole alone in
             terms of cure rates and egg reduction rates against T. trichiura infections in children
             aged 6-12 years in Uganda?
  
          -  Is single oral dose combined ivermectin-albendazole superior to albendazole alone in
             terms of cure rates and egg reduction rates against co-infecting soil-transmitted
             helminth infections such as Ascaris lumbricoides and hookworm in children aged 6-12
             years in Uganda?
  
          -  Is single oral dose combined ivermectin-albendazole as tolerable and safe as albendazole
             monotherapy in children aged 6-12 years in Uganda?
  
        Participants will be asked to provide two stool samples at baseline that will be subjected to
        microscopic analysis using the Kato-Katz thick smear technique for detection of
        soil-transmitted helminth eggs. T. trichiura-infected participants will be:
  
          -  clinically examined for general health, anthropometric parameters including height and
             weight as well as temperature
  
          -  randomly assigned to either receive one single oral dose of combined ivermectin and
             albendazole or albendazole monotherapy
  
          -  checked for any potential adverse events and will undergo a brief questionnaire on
             specific symptoms 3h after drug administration
  
          -  asked to provide another two stool samples to be microscopically examined for helminth
             eggs 14-21 days post-treatment Researchers will compare individuals treated with
             ivermectin-albendazole and albendazole alone to see if the proportion of T. trichiura
             egg-negative individuals and/or reduction in egg counts differs between these two groups
             14-21 days after treatment.
  In view that efficacy of co-administered ivermectin (IVM) and albendazole (ALB) has been
        found to vary between different settings the rationale of this parallel open-label randomized
        controlled superiority trial is to provide evidence on the efficacy of co-administered
        ivermectin and albendazole compared to albendazole monotherapy in school-aged children aged
        6-12 years against infection with T. trichiura in Uganda.
  
        Our primary objective is to demonstrate superiority of
  
          1. Arm A: single dose of ivermectin (200 µg/kg, 3 mg tablets according to weight) / single
             dose of albendazole (400 mg tablet) combination, compared to
  
          2. Arm B: single dose of albendazole (400 mg tablet)
  
        in terms of cure rate (CR) against T. trichiura infections in school-aged children aged 6-12
        years assessed at 14-21 days post-treatment by Kato-Katz microscopy.
  
        The secondary objectives of the trial are:
  
          1. to determine the egg reduction rates (ERRs) of ivermectin/albendazole combination
             therapy compared to albendazole monotherapy against T. trichiura
  
          2. to determine the CRs and ERRs of the study drugs against Ascaris lumbricoides and
             hookworm in co-infected participants
  
          3. to evaluate the safety and tolerability of the treatment
  
        The study will be implemented as a school-based study and children aged 6-12 years from two
        primary schools in Kabale district, southwestern Uganda will be invited for parasitological
        examination after obtaining informed consent from parents/caregivers and assent by the minor
        participants. Two stool samples will be collected, when possible, on two consecutive days.
        Children found to be infected with T. trichiura based on quadruplicate Kato-Katz thick smear
        readings will be enrolled into the actual trial. The medical history of the participants will
        be assessed with a standardized questionnaire, in addition to a clinical examination carried
        out by the study nurse/physician before treatment.
  
        All participants will be interviewed before treatment and after 3 and 24 hours (active
        surveillance) for the occurrence of adverse events (AEs). Participants and their caregivers
        will be told that any potential AEs happening between 24 hours and the respective follow-up
        time point for stool collection should be reported to the local village health team (VHT)
        members, which will be trained to handle the situation by taking the participant to a health
        facility for timely treatment, or to local health workers directly.
  
        The efficacy of the treatment will be determined at 14-21 days post-treatment by collecting
        another two stool samples.
  
        At both, baseline and follow-up (14-21 days post treatment) a portion of stool (1.5-2 g) from
        all participants identified with T. trichiura infections will be preserved in 95% ethanol,
        shipped to a reference laboratory in Switzerland and subjected to amplicon deep sequencing
        for characterization of T. trichiura strains and investigation of potential resistance
        markers.
  
        Study participants eligible for treatment will be randomly assigned to one of the two
        treatment arms stratified by 2 levels of baseline infection intensity (light: 1-999 EPG, and
        moderate plus heavy: ≥ 1000 EPG T. trichiura infections).
  
        The primary analysis will include all participants with primary end point data (available
        case analysis). Supplementary, a per-protocol analysis will be conducted. CRs will be
        calculated as the percentage of egg-positive subjects at baseline who become egg-negative
        after treatment. Differences among CRs (between treatment arms) will be analyzed by using
        crude and adjusted logistic regression modeling.
  
        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 differences in
        ERRs.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Parallel open-label randomized controlled superiority trial
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: Allocation concealment will be warranted using sequential, opaque, sealed envelopes. Outcome assessors in the lab will be blinded.
  measure: Number of Participants T. Trichiura Egg Negative Post-Treatment (Cured)
  time frame: 14-21 days after treatment
  description: The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR).
  measure: Egg Reduction Rate (ERR) against T. Trichiura
  time frame: 14-21 days after 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. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.
  measure: Number of Participants With Concomitant Soil-transmitted Helminth Infections Egg Negative Post-Treatment (Cured)
  time frame: 14-21 days after treatment
  description: Number of participants that converted from egg positive with Ascaris lumbricoides and/or hookworm infections to egg negative after 14-21 days.
  measure: Egg-reduction Rates (ERRs) Against Concomitant Soil-transmitted Helminth Infections
  time frame: 14-21 days after treatment
  description: Percent change in geometric mean eggs per gram of stool from before to after treatment. ERRs will be calculated for Ascaris lumbricoides and hookworm infections as described in outcome 2.
  arm group label: IVM (200 µg/kg) + ALB (400 mg)
  arm group type: Experimental
  description: A single tablet of albendazole (400mg) plus 200 µg/kg of ivermectin, provided as single oral dose.
  arm group label: ALB (400mg)
  arm group type: Active Comparator
  description: A single tablet of albendazole (400mg), provided as single oral dose.
  intervention type: Drug
  intervention name: IVM (200 µg/kg) + ALB (400 mg)
  description: World Health Organization Pre-Qualification (WHO PQ) recommended ivermectin 3mg tablets will be used together with albendazole 400mg tablets as provided by WHO for Neglected Tropical Disease (NTD) programs.
  arm group label: IVM (200 µg/kg) + ALB (400 mg)
  other name: Zentel® and Stromectol®, Ivermectin Tablet 3mg
  intervention type: Drug
  intervention name: ALB (400mg)
  description: Albendazole 400mg manufactured and donated by GlaxoSmithKline (GSK) to WHO
  arm group label: ALB (400mg)
  other name: Zentel®
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 12 Years
  healthy volunteers: No
  last name: Jennifer Keiser, Prof
  phone: +41612848218
  email: jennifer.keiser@swisstph.ch
  facility: 
  contact: 
  country: Uganda
  responsible party type: Sponsor-Investigator
  investigator affiliation: Swiss Tropical & Public Health Institute
  investigator full name: Jennifer Keiser
  investigator title: Prof. Dr.
  mesh term: Trichuriasis
  mesh term: Ivermectin
  mesh term: Albendazole
  sharing ipd: Undecided