<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/NCT03278431</url>
  </required_header>
  <id_info>
    <org_study_id>TRICOMBI01032017</org_study_id>
    <nct_id>NCT03278431</nct_id>
  </id_info>
  <brief_title>Triple Combinations Against Hookworm Infections in Lao</brief_title>
  <acronym>Tricombi</acronym>
  <official_title>Different Drug Combinations Against Hookworm Infection in School-aged Children in the Lao People's Democratic Republic, a Single Blind, Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Swiss Tropical &amp; Public Health Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      More than one billion people are infected with soil-transmitted helminths (STH, A.&#xD;
      lumbricoides, hookworm or Trichuris trichiura). Preventive chemotherapy - i.e. annual or&#xD;
      biannual treatment of at-risk populations with albendazole or mebendazole is the current&#xD;
      strategy against STH. However, the efficacy of both drugs is only moderate against hookworm&#xD;
      and low against T. trichiura. For increasing the efficacy and to avoid drug resistance, new&#xD;
      drugs or the combination of different drugs is the way forward.&#xD;
&#xD;
      In this randomised controlled trial, we assess the efficacy (based on cure rates) of&#xD;
      different drug combinations in school-aged children in Lao. 420 hookworm positive children&#xD;
      will be treated: 140 with albendazole-oxantel pamoate, 140 with albendazole-pyrantel&#xD;
      pamoate-oxantel pamoate treatment arms, 70 with pyrantel pamoate-oxantel pamoate and 70 with&#xD;
      mebendazole-pyrantel pamoate-oxantel pamoate. Two stool samples will be collected at baseline&#xD;
      and follow-up (14-21 days after treatment) and analysed with Kato-Katz.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      More than one billion people are infected with A. lumbricoides, hookworm or Trichuris&#xD;
      trichiura, the so-called soil-transmitted helminths (STH). Preventive chemotherapy - i.e.&#xD;
      annual or biannual treatment of at-risk populations, is the current strategy against STH&#xD;
      advocated by the World Health Organization. However, the currently used drugs albendazole and&#xD;
      mebendazole have only moderate efficacy against hookworm and low against T. trichiura. The&#xD;
      main challenge is their temporal decrease in efficacy, which might be associated with drug&#xD;
      resistance, as it was shown in veterinary medicine. For increasing the efficacy and to avoid&#xD;
      drug resistance, new drugs or the combination of different drugs is the way forward.&#xD;
&#xD;
      The primary objective of this study is to assess the efficacy (based on cure rates [CR]) of&#xD;
      the three combinations, i.e. albendazole-oxantel pamoate, pyrantel pamoate-oxantel pamoate&#xD;
      and albendazole-pyrantel pamoate-oxantel pamoate in school-aged children infected with&#xD;
      hookworms in Laos. Secondary objectives include; i) a proof of concept, investigating the&#xD;
      difference between the two triple combinations albendazole-pyrantel pamoate-oxantel pamoate&#xD;
      versus mebendazole-pyrantel pamoate-oxantel pamoate (based on CRs), ii) egg reduction rates&#xD;
      (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura and iii)&#xD;
      tolerability of the 4 combinations.&#xD;
&#xD;
      Two stool samples will be collected from school-aged children (age 6-15) at baseline. 420&#xD;
      hookworm positive children will be treated: 140 with albendazole-oxantel pamoate, 140 with&#xD;
      albendazole-pyrantel pamoate-oxantel pamoate, 70 with pyrantel pamoate-oxantel pamoate and 70&#xD;
      with mebendazole-pyrantel pamoate-oxantel pamoate treatment arms The medical history of the&#xD;
      participating children will be assessed with a standardized questionnaire, in addition to a&#xD;
      clinical examination carried out by the study physician on the treatment day. Children will&#xD;
      be interviewed before treatment for clinical symptoms and 3 and 24 hours after 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. All stool samples will be&#xD;
      examined with duplicated Kato-Katz thick smears.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 27, 2017</start_date>
  <completion_date type="Actual">December 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 17, 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>Single (Participant)</masking>
    <masking_description>Single-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cure rates of three drug combinations</measure>
    <time_frame>14-21 days after treatment</time_frame>
    <description>to comparatively assess the efficacy (based on cure rates, CR) i) albendazole-oxantel pamoate, ii) pyrantel pamoate-oxantel pamoate, iii) albendazole-pyrantel pamoate-oxantel pamoate in school-aged children infected with hookworms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cure rates against hookworm of the two triple combinations</measure>
    <time_frame>14-21 days after treatment</time_frame>
    <description>To assess the CRs against hookworm of albendazole-pyrantel pamoate-oxantel pamoate versus mebendazole-pyrantel pamoate-oxantel pamoate (proof of concept)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Egg reduction rates (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura</measure>
    <time_frame>14-21 days after treatment</time_frame>
    <description>Assessing the egg reduction rates (ERR) against hookworm and ERRs and cure rates (CR) against A. lumbricoides and T. trichiura</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events 3 and 24 hours after treatment</measure>
    <time_frame>3 and 24 hours after treatment</time_frame>
    <description>Participants will be interviewed using a standardized questionnaire, before treatment for clinical symptoms and 3 and 24 hours after treatment about the occurrence of adverse events.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">420</enrollment>
  <condition>Hookworm Infection</condition>
  <arm_group>
    <arm_group_label>Albendazole triple combi</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Albendazole (400 mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pyrantel pamoate double combi</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Albendazole double combi</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Albendazole (400 mg) + oxantel pamoate (20 mg/kg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mebendazole triple combi</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mebendazole (500mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albendazole</intervention_name>
    <description>Albendazole (400 mg) from Janssen, donated by the World Health Organization</description>
    <arm_group_label>Albendazole double combi</arm_group_label>
    <arm_group_label>Albendazole triple combi</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pyrantel Pamoate</intervention_name>
    <description>Pyrantel pamoate (20 mg/kg), will be purchased by the World Health Organization</description>
    <arm_group_label>Albendazole triple combi</arm_group_label>
    <arm_group_label>Mebendazole triple combi</arm_group_label>
    <arm_group_label>Pyrantel pamoate double combi</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxantel Pamoate</intervention_name>
    <description>Oxantel pamoate (20mg/kg) will be produced by the University of Basel</description>
    <arm_group_label>Albendazole double combi</arm_group_label>
    <arm_group_label>Albendazole triple combi</arm_group_label>
    <arm_group_label>Mebendazole triple combi</arm_group_label>
    <arm_group_label>Pyrantel pamoate double combi</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mebendazole</intervention_name>
    <description>Mebendazole (500 mg) from GlaxoSmithKline, donated by the World Health Organization</description>
    <arm_group_label>Mebendazole triple combi</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent signed by parents and/or legal representative; and a verbal&#xD;
             assent (children &lt;12 years) or signed assent (children ≥12 years), according to Lao&#xD;
             regulations.&#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 two to&#xD;
             three weeks after treatment (follow-up).&#xD;
&#xD;
          -  Positive for hookworm eggs in the stool.&#xD;
&#xD;
          -  Absence of major systemic illnesses, e.g. diabetes, severe anemia as assessed by a&#xD;
             medical doctor, 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).&#xD;
&#xD;
          -  No known allergy to study medications (e.g. albendazole, mebendazole, pyrantel&#xD;
             pamoate, oxantel pamoate).&#xD;
&#xD;
          -  Negative pregnancy test (girls ≥12 years)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No written informed consent by parents and/or legal representative and no verbal&#xD;
             assent (children &lt;12 years) or signed assent (children ≥12 years).&#xD;
&#xD;
          -  Presence of major systemic illnesses, e.g. diabetes, severe anemia as assessed by a&#xD;
             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.&#xD;
&#xD;
          -  Positive pregnancy test (girls ≥12 years)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Nambak District Hospital</name>
      <address>
        <city>Luang Prabang</city>
        <zip>0604</zip>
        <country>Lao People's Democratic Republic</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lao People's Democratic Republic</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 6, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>May 7, 2018</last_update_submitted>
  <last_update_submitted_qc>May 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal 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</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Hookworm Infections</mesh_term>
    <mesh_term>Ancylostomiasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Albendazole</mesh_term>
    <mesh_term>Mebendazole</mesh_term>
    <mesh_term>Piperazine</mesh_term>
    <mesh_term>Piperazine citrate</mesh_term>
    <mesh_term>Pyrantel</mesh_term>
    <mesh_term>Pyrantel Pamoate</mesh_term>
    <mesh_term>Oxantel</mesh_term>
    <mesh_term>Oxantel pamoate</mesh_term>
    <mesh_term>DMP 777</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03278431
org study id: TRICOMBI01032017
nct id: NCT03278431
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
More than one billion people are infected with soil-transmitted helminths (STH, A.
      lumbricoides, hookworm or Trichuris trichiura). Preventive chemotherapy - i.e. annual or
      biannual treatment of at-risk populations with albendazole or mebendazole is the current
      strategy against STH. However, the efficacy of both drugs is only moderate against hookworm
      and low against T. trichiura. For increasing the efficacy and to avoid drug resistance, new
      drugs or the combination of different drugs is the way forward.

      In this randomised controlled trial, we assess the efficacy (based on cure rates) of
      different drug combinations in school-aged children in Lao. 420 hookworm positive children
      will be treated: 140 with albendazole-oxantel pamoate, 140 with albendazole-pyrantel
      pamoate-oxantel pamoate treatment arms, 70 with pyrantel pamoate-oxantel pamoate and 70 with
      mebendazole-pyrantel pamoate-oxantel pamoate. Two stool samples will be collected at baseline
      and follow-up (14-21 days after treatment) and analysed with Kato-Katz.
More than one billion people are infected with A. lumbricoides, hookworm or Trichuris
      trichiura, the so-called soil-transmitted helminths (STH). Preventive chemotherapy - i.e.
      annual or biannual treatment of at-risk populations, is the current strategy against STH
      advocated by the World Health Organization. However, the currently used drugs albendazole and
      mebendazole have only moderate efficacy against hookworm and low against T. trichiura. The
      main challenge is their temporal decrease in efficacy, which might be associated with drug
      resistance, as it was shown in veterinary medicine. For increasing the efficacy and to avoid
      drug resistance, new drugs or the combination of different drugs is the way forward.

      The primary objective of this study is to assess the efficacy (based on cure rates [CR]) of
      the three combinations, i.e. albendazole-oxantel pamoate, pyrantel pamoate-oxantel pamoate
      and albendazole-pyrantel pamoate-oxantel pamoate in school-aged children infected with
      hookworms in Laos. Secondary objectives include; i) a proof of concept, investigating the
      difference between the two triple combinations albendazole-pyrantel pamoate-oxantel pamoate
      versus mebendazole-pyrantel pamoate-oxantel pamoate (based on CRs), ii) egg reduction rates
      (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura and iii)
      tolerability of the 4 combinations.

      Two stool samples will be collected from school-aged children (age 6-15) at baseline. 420
      hookworm positive children will be treated: 140 with albendazole-oxantel pamoate, 140 with
      albendazole-pyrantel pamoate-oxantel pamoate, 70 with pyrantel pamoate-oxantel pamoate and 70
      with mebendazole-pyrantel pamoate-oxantel pamoate treatment arms The medical history of the
      participating children will be assessed with a standardized questionnaire, in addition to a
      clinical examination carried out by the study physician on the treatment day. Children will
      be interviewed before treatment for clinical symptoms and 3 and 24 hours after 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. All stool samples will be
      examined with duplicated Kato-Katz thick smears.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
masking description: Single-blind
measure: Cure rates of three drug combinations
time frame: 14-21 days after treatment
description: to comparatively assess the efficacy (based on cure rates, CR) i) albendazole-oxantel pamoate, ii) pyrantel pamoate-oxantel pamoate, iii) albendazole-pyrantel pamoate-oxantel pamoate in school-aged children infected with hookworms.
measure: Cure rates against hookworm of the two triple combinations
time frame: 14-21 days after treatment
description: To assess the CRs against hookworm of albendazole-pyrantel pamoate-oxantel pamoate versus mebendazole-pyrantel pamoate-oxantel pamoate (proof of concept)
measure: Egg reduction rates (ERR) against hookworm and ERRs/CRs against A. lumbricoides and T. trichiura
time frame: 14-21 days after treatment
description: Assessing the egg reduction rates (ERR) against hookworm and ERRs and cure rates (CR) against A. lumbricoides and T. trichiura
measure: Incidence of adverse events 3 and 24 hours after treatment
time frame: 3 and 24 hours after treatment
description: Participants will be interviewed using a standardized questionnaire, before treatment for clinical symptoms and 3 and 24 hours after treatment about the occurrence of adverse events.
arm group label: Albendazole triple combi
arm group type: Active Comparator
description: Albendazole (400 mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)
arm group label: Pyrantel pamoate double combi
arm group type: Experimental
description: Pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)
arm group label: Albendazole double combi
arm group type: Experimental
description: Albendazole (400 mg) + oxantel pamoate (20 mg/kg)
arm group label: Mebendazole triple combi
arm group type: Experimental
description: Mebendazole (500mg) + pyrantel pamoate (20 mg/kg) + oxantel pamoate (20 mg/kg)
intervention type: Drug
intervention name: Albendazole
description: Albendazole (400 mg) from Janssen, donated by the World Health Organization
arm group label: Albendazole double combi
arm group label: Albendazole triple combi
intervention type: Drug
intervention name: Pyrantel Pamoate
description: Pyrantel pamoate (20 mg/kg), will be purchased by the World Health Organization
arm group label: Albendazole triple combi
arm group label: Mebendazole triple combi
arm group label: Pyrantel pamoate double combi
intervention type: Drug
intervention name: Oxantel Pamoate
description: Oxantel pamoate (20mg/kg) will be produced by the University of Basel
arm group label: Albendazole double combi
arm group label: Albendazole triple combi
arm group label: Mebendazole triple combi
arm group label: Pyrantel pamoate double combi
intervention type: Drug
intervention name: Mebendazole
description: Mebendazole (500 mg) from GlaxoSmithKline, donated by the World Health Organization
arm group label: Mebendazole triple combi
criteria: 
gender: All
minimum age: 6 Years
maximum age: 15 Years
healthy volunteers: No
facility: 
country: Lao People's Democratic Republic
responsible party type: Principal Investigator
investigator affiliation: Swiss Tropical & Public Health Institute
investigator full name: Jennifer Keiser
investigator title: Prof
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Hookworm Infections
mesh term: Ancylostomiasis
mesh term: Albendazole
mesh term: Mebendazole
mesh term: Piperazine
mesh term: Piperazine citrate
mesh term: Pyrantel
mesh term: Pyrantel Pamoate
mesh term: Oxantel
mesh term: Oxantel pamoate
mesh term: DMP 777
sharing ipd: No