<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/NCT04411836</url>
  </required_header>
  <id_info>
    <org_study_id>EFFORT</org_study_id>
    <nct_id>NCT04411836</nct_id>
  </id_info>
  <brief_title>Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine</brief_title>
  <acronym>EFFORT</acronym>
  <official_title>Effectiveness of Novel Approaches to Radical Cure With Tafenoquine and Primaquine - a Randomized Controlled Trial in P. Vivax Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Menzies School of Health Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Melbourne</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Centre for Parasitology, Entomology and Malaria Control, Cambodia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mahidol Oxford Tropical Medicine Research Unit</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ethiopian Public Health Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universitas Sumatera Utara</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Arba Minch University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Menzies School of Health Research</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Health care facility based, randomized, controlled, open label, superiority trial with 3 arms&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  To assess the effectiveness of a short-course of high dose primaquine (total dose 7mg/kg&#xD;
           given unsupervised over 7 days) compared to the current standard low dose primaquine&#xD;
           regimen (total dose 3.5mg/kg given unsupervised over 14 days).&#xD;
&#xD;
        -  To assess the effectiveness of tafenoquine (single dose of 300mg) compared to the&#xD;
           short-course high dose primaquine regimen.&#xD;
&#xD;
        -  To assess the safety of tafenoquine compared to the high and low dose primaquine&#xD;
           regimens.&#xD;
&#xD;
        -  To assess the cost-effectiveness and feasibility of high dose primaquine and tafenoquine&#xD;
           compared to the current low dose primaquine regimen&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 25, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence risk any P vivax PQ7 / PQ14</measure>
    <time_frame>6 months</time_frame>
    <description>The incidence risk (time to first event) of any P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence risk any P vivax PQ7 / TQ</measure>
    <time_frame>6 months</time_frame>
    <description>The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence risk symptomatic P vivax TQ / PQ14</measure>
    <time_frame>6 months</time_frame>
    <description>The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between TQ and the control arm (PQ14).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence risk any P vivax PQ7 / PQ14</measure>
    <time_frame>6 months</time_frame>
    <description>The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence risk any P vivax PQ7 / TQ</measure>
    <time_frame>6 months</time_frame>
    <description>• The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence risk any P vivax PQ14 / TQ</measure>
    <time_frame>6 months</time_frame>
    <description>The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ14 and TQ arms</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">960</enrollment>
  <condition>Vivax Malaria</condition>
  <condition>Plasmodium Vivax</condition>
  <condition>Malaria, Vivax</condition>
  <condition>Malaria Relapse</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients are treated with schizontocidal treatment plus low dose PQ (total dose 3.5mg/kg) unsupervised over 14 days (PQ14)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PQ Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TQ Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tafenoquine</intervention_name>
    <description>patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ).</description>
    <arm_group_label>TQ Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Primaquine</intervention_name>
    <description>patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7)</description>
    <arm_group_label>PQ Intervention</arm_group_label>
    <other_name>Primaquine 7 days</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  P. vivax peripheral parasitaemia (mono-infection) as determined by microscopy&#xD;
&#xD;
          -  G6PD normal status (G6PD activity ≥ 70% of the adjusted male median as determined by&#xD;
             the Biosensor™ (SD Biosensor, ROK))&#xD;
&#xD;
          -  Fever (temperature ≥37.5⁰C) or history of fever in the preceding 48 hours&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Living in the study area and willing to be followed for six months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Danger signs or symptoms of severe malaria&#xD;
&#xD;
          -  Anaemia (defined as Hb &lt;8g/dl)&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Known hypersensitivity to any of the study drugs&#xD;
&#xD;
          -  Regular use of drugs with haemolytic potential&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kamala Thriemer, MD, MPH, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Menzies School of Health Research</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kamala Thriemer, MD, MPH, PhD</last_name>
    <phone>0889468644</phone>
    <email>kamala.ley-thriemer@menzies.edu.au</email>
  </overall_contact>
  <location>
    <facility>
      <name>Kravanh District Hospital</name>
      <address>
        <city>Pursat</city>
        <state>Pursat Province</state>
        <country>Cambodia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rupam Tripura, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lorenz von Seidlein, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lek Dysoley, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rupam Tripura, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tom Peto, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>James Callery, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Chambak Health Center</name>
      <address>
        <city>Kampong Speu</city>
        <country>Cambodia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Rupam Tripura, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lorenz Seidlein, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lek Dysoley, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>James Callery, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thomas Peto, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rupam Tripura, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Siem Pang Health Centre</name>
      <address>
        <city>Stung Treng</city>
        <country>Cambodia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rupam Tripura, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lorenz von Seidlein, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lek Dysoley, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rupam Tripura, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tom Peto, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>James Callery, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Arba Minch General Hospital</name>
      <address>
        <city>Arba Minch</city>
        <country>Ethiopia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tamiru Shibiru Degaga, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tanjung Leidong Health Center</name>
      <address>
        <city>Labuhanbatu</city>
        <state>Sumatera</state>
        <country>Indonesia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ayodhia Pasaribu Pitaloka, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Aga Khan Hospital Karachi</name>
      <address>
        <city>Karachi</city>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Asim Beg, MD</last_name>
    </contact>
    <investigator>
      <last_name>Asim Beg, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Najia Ghanchi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Momin Kazi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Farah Qamar, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Cambodia</country>
    <country>Ethiopia</country>
    <country>Indonesia</country>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 19, 2023</last_update_submitted>
  <last_update_submitted_qc>June 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tafenoquine</keyword>
  <keyword>primaquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Malaria, Vivax</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primaquine</mesh_term>
    <mesh_term>Tafenoquine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study Protocol and Statistical Analysis Plan will be made available to others. Data collected for the study, including individual patient data and the final trial dataset are reserved for the chief investigator and co-investigators of the trial. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Trial results will be published in peer-reviewed open access journals and disseminated to trial stakeholders, including participants, as per ethical guidelines.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_access_criteria>The data are available for access via the WorldWide Antimalarial Resistance Network (WWARN.org). Requests for access will be reviewed by a Data Access Committee to ensure that use of data protects the interests of the participants and researchers according to the terms of ethics approval and principles of equitable data sharing. Requests can be submitted by email to malariaDAC@iddo.org via the Data Access Form available at WWARN.org/accessing-data. The WWARN is registered with the Registry of Research Data Repositories (re3data.org).</ipd_access_criteria>
    <ipd_url>http://WWARN.org/accessing-data</ipd_url>
  </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/NCT04411836
org study id: EFFORT
nct id: NCT04411836
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Health care facility based, randomized, controlled, open label, superiority trial with 3 arms
-  To assess the effectiveness of a short-course of high dose primaquine (total dose 7mg/kg
           given unsupervised over 7 days) compared to the current standard low dose primaquine
           regimen (total dose 3.5mg/kg given unsupervised over 14 days).

        -  To assess the effectiveness of tafenoquine (single dose of 300mg) compared to the
           short-course high dose primaquine regimen.

        -  To assess the safety of tafenoquine compared to the high and low dose primaquine
           regimens.

        -  To assess the cost-effectiveness and feasibility of high dose primaquine and tafenoquine
           compared to the current low dose primaquine regimen
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence risk any P vivax PQ7 / PQ14
time frame: 6 months
description: The incidence risk (time to first event) of any P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).
measure: Incidence risk any P vivax PQ7 / TQ
time frame: 6 months
description: The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms
measure: Incidence risk symptomatic P vivax TQ / PQ14
time frame: 6 months
description: The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between TQ and the control arm (PQ14).
measure: Incidence risk any P vivax PQ7 / PQ14
time frame: 6 months
description: The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 6-month follow up period as determined by microscopy compared between the PQ7 arm and the control arm (PQ14).
measure: Incidence risk any P vivax PQ7 / TQ
time frame: 6 months
description: • The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ7 and TQ arms
measure: Incidence risk any P vivax PQ14 / TQ
time frame: 6 months
description: The incidence risk (time to first event) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy compared between PQ14 and TQ arms
arm group label: Control
arm group type: No Intervention
description: Patients are treated with schizontocidal treatment plus low dose PQ (total dose 3.5mg/kg) unsupervised over 14 days (PQ14)
arm group label: PQ Intervention
arm group type: Experimental
description: Patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7)
arm group label: TQ Intervention
arm group type: Experimental
description: Patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ)
intervention type: Drug
intervention name: Tafenoquine
description: patients are treated with schizontocidal treatment plus a single dose of Tafenoquine (TQ).
arm group label: TQ Intervention
intervention type: Drug
intervention name: Primaquine
description: patients are treated with schizontocidal treatment plus high dose PQ (total dose 7 mg/kg) unsupervised over 7 days (PQ7)
arm group label: PQ Intervention
other name: Primaquine 7 days
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Kamala Thriemer, MD, MPH, PhD
role: Principal Investigator
affiliation: Menzies School of Health Research
last name: Kamala Thriemer, MD, MPH, PhD
phone: 0889468644
email: kamala.ley-thriemer@menzies.edu.au
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Cambodia
country: Ethiopia
country: Indonesia
country: Pakistan
responsible party type: Sponsor
mesh term: Malaria
mesh term: Malaria, Vivax
mesh term: Primaquine
mesh term: Tafenoquine
sharing ipd: Yes
ipd description: Study Protocol and Statistical Analysis Plan will be made available to others. Data collected for the study, including individual patient data and the final trial dataset are reserved for the chief investigator and co-investigators of the trial. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Trial results will be published in peer-reviewed open access journals and disseminated to trial stakeholders, including participants, as per ethical guidelines.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd access criteria: The data are available for access via the WorldWide Antimalarial Resistance Network (WWARN.org). Requests for access will be reviewed by a Data Access Committee to ensure that use of data protects the interests of the participants and researchers according to the terms of ethics approval and principles of equitable data sharing. Requests can be submitted by email to malariaDAC@iddo.org via the Data Access Form available at WWARN.org/accessing-data. The WWARN is registered with the Registry of Research Data Repositories (re3data.org).
ipd url: http://WWARN.org/accessing-data