<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/NCT01680406</url>
  </required_header>
  <id_info>
    <org_study_id>CDC-CGH-6338</org_study_id>
    <nct_id>NCT01680406</nct_id>
  </id_info>
  <brief_title>Ethiopia Antimalarial in Vivo Efficacy Study 2012</brief_title>
  <official_title>Ethiopia Antimalarial in Vivo Efficacy Study 2012: Evaluating the Efficacy of Artemether-lumefantrine Alone Compared to Artemether-lumefantrine Plus Primaquine and Chloroquine Alone Compared to Chloroquine Plus Primaquine for Plasmodium Vivax Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ethiopian Health and Nutrition Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Federal Minstry of Health of Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oromia Regional Health Bureau, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>United States Agency for International Development (USAID)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Menzies School of Health Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centers for Disease Control and Prevention</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that the addition of primaquine (PQ) to both&#xD;
      artemether-lumefantrine (AL) and chloroquine (CQ) for the treatment of Plasmodium vivax&#xD;
      infection will result in decreased chance of relapse by about 60%.&#xD;
&#xD;
      The investigators plan to assess the therapeutic efficacy of AL compared to combined AL + PQ&#xD;
      and CQ compared to combined CQ + PQ against P. vivax infection. They also plan to determine&#xD;
      the number of recurrent vivax episodes in patients receiving PQ compared to those who don't&#xD;
      receive PQ. Patients aged above 1 year with symptomatic malaria presenting to health centers&#xD;
      will be enrolled for treatment with AL, AL+PQ, CQ, or CQ+PQ for P. vivax infection.&#xD;
&#xD;
      Phase 1 of the study will monitor the clinical, parasitological, and hematological parameters&#xD;
      for P. vivax infection over a 42-day follow-up period, which will be used to evaluate drug&#xD;
      efficacy. Phase 2 will continue monthly follow-up of these patients for one year to assess&#xD;
      frequency of recurring vivax infections. Results from this research study will be used to&#xD;
      assist Ethiopia in assessing their current national malaria drug policies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following the rapid development of significant drug resistance of Plasmodium falciparum (Pf)&#xD;
      to chloroquine and then sulfadoxine-pyrimethamine, artemether- lumefantrine (Coartem or AL)&#xD;
      was adopted as first line therapy in Ethiopia in 2004. According to the current national&#xD;
      malaria diagnosis and treatment guidelines updated in 2012, first-line treatment for&#xD;
      uncomplicated P. falciparum infection is AL. First-line treatment for Plasmodium vivax (Pv)&#xD;
      is chloroquine (CQ) alone in malarious areas and with primaquine in non-malarious areas at&#xD;
      health center and hospital level. WHO recommends treatment of Pv with CQ or an&#xD;
      artemisinin-based combination therapy (ACT) in combination with primaquine. For all clinical&#xD;
      infection without laboratory confirmation, AL is the first-line treatment since AL is&#xD;
      effective against both Pf and Pv. Thus, in Ethiopia, where treatment for malaria without&#xD;
      laboratory confirmation occurs frequently, Pv is often treated with AL as the standard of&#xD;
      care. Similarly, the recommended drug for mixed infection with Pf and Pv is AL. Now with&#xD;
      wide-spread use of AL and CQ and with evidence that malaria laboratory testing is occurring&#xD;
      in about half of those suspected with clinical evidence of malaria infection, the&#xD;
      investigators propose to conduct an antimalarial efficacy study to monitor the effectiveness&#xD;
      of these therapies in Ethiopia and to determine how efficacious these drugs remain for Pv. In&#xD;
      addition, with high rates of relapse with P. vivax infection, the efficacy and safety of&#xD;
      co-administering primaquine will be assessed. This information will inform future policy&#xD;
      changes with respect to appropriate antimalarial strategies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>P. vivax treatment failures following treatment with AL compared to AL+PQ</measure>
    <time_frame>day 28 and 42</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>P. vivax treatment failures following treatment with CQ compared to CQ+PQ</measure>
    <time_frame>day 28 and 42</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of episodes of P. vivax parasitemia over one year following initial effective therapy against P. vivax (i.e. parasite clearance)</measure>
    <time_frame>1 year after day 0 of enrollment</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety endpoint</measure>
    <time_frame>baseline (day 0) and day 28</time_frame>
    <description>Change in hemoglobin concentration</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">398</enrollment>
  <condition>Plasmodium Vivax Infection</condition>
  <arm_group>
    <arm_group_label>Artemether-lumefantrine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Weight-based dose to be administered as fixed-dose combination twice daily for three days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Artemether-lumefantrine and primaquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artemether-lumefantrine will be given in a weight-based dose to be administered as fixed-dose combination twice daily for three days.&#xD;
Primaquine will be given beginning on day 2 of artemether-lumefantrine to patients with a normal G6PD test; dose is weight-based to be administered once daily for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chloroquine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Chloroquine will be given in a weight-based dose to be administered once daily for three days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chloroquine and primaquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Chloroquine will be given in a weight-based dose to be administered once daily for three days.&#xD;
Primaquine will be given beginning on day 2 of chloroquine to patients with a normal G6PD test; dose is weight-based to be administered once daily for 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Artemether-lumefantrine combination</intervention_name>
    <arm_group_label>Artemether-lumefantrine</arm_group_label>
    <arm_group_label>Artemether-lumefantrine and primaquine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Primaquine</intervention_name>
    <arm_group_label>Artemether-lumefantrine and primaquine</arm_group_label>
    <arm_group_label>Chloroquine and primaquine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chloroquine</intervention_name>
    <arm_group_label>Chloroquine</arm_group_label>
    <arm_group_label>Chloroquine and primaquine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Slide-confirmed infection with P. vivax&#xD;
&#xD;
          -  Age &gt; 1 year&#xD;
&#xD;
          -  Lives within 20 km of the enrolling health facility&#xD;
&#xD;
          -  Weight ≥ 5.0 kg&#xD;
&#xD;
          -  Axillary temperature ≥ 37.5º C or history of fever during the previous 48 hours&#xD;
&#xD;
          -  Patient or caregiver agrees to all finger pricks and return visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  General danger signs or symptoms of severe malaria (see Annex II)&#xD;
&#xD;
          -  Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard&#xD;
             deviations below the mean (NCHS/WHO normalized reference values)&#xD;
&#xD;
          -  Slide confirmed infection with any other Plasmodium species. besides P. vivax&#xD;
             mono-infection&#xD;
&#xD;
          -  Acute anemia, defined as Hg &lt; 8 g/dl&#xD;
&#xD;
          -  Known hypersensitivity to any of the drugs being evaluated&#xD;
&#xD;
          -  Presence of febrile conditions caused by diseases other than malaria&#xD;
&#xD;
          -  Serious or chronic medical condition by history (cardiac, renal, hepatic diseases,&#xD;
             sickle cell disease, HIV/AIDS)&#xD;
&#xD;
          -  Pregnant or breastfeeding women.&#xD;
&#xD;
          -  History or hemolysis or severe anemia&#xD;
&#xD;
          -  Regular medication, which may interfere with antimalarial pharmacokinetics&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jimee Hwang, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centers for Disease Control and Prevention</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tesfay Abreha, MSc, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>ICAP-Columbia University, Addis Ababa, Ethiopia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Hoos, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>ICAP-Columbia University, New York, USA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bishoftu Malaria Center</name>
      <address>
        <city>Debre Zeit</city>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Batu Health Center</name>
      <address>
        <city>Zeway</city>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Plasmodium vivax</keyword>
  <keyword>malaria</keyword>
  <keyword>Ethiopia</keyword>
  <keyword>Sub-Saharan Africa</keyword>
  <keyword>primaquine</keyword>
  <keyword>artemether lumefantrine</keyword>
  <keyword>chloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chloroquine</mesh_term>
    <mesh_term>Lumefantrine</mesh_term>
    <mesh_term>Artemether</mesh_term>
    <mesh_term>Primaquine</mesh_term>
    <mesh_term>Artemether, Lumefantrine Drug Combination</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01680406
org study id: CDC-CGH-6338
nct id: NCT01680406
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The investigators hypothesize that the addition of primaquine (PQ) to both
      artemether-lumefantrine (AL) and chloroquine (CQ) for the treatment of Plasmodium vivax
      infection will result in decreased chance of relapse by about 60%.

      The investigators plan to assess the therapeutic efficacy of AL compared to combined AL + PQ
      and CQ compared to combined CQ + PQ against P. vivax infection. They also plan to determine
      the number of recurrent vivax episodes in patients receiving PQ compared to those who don't
      receive PQ. Patients aged above 1 year with symptomatic malaria presenting to health centers
      will be enrolled for treatment with AL, AL+PQ, CQ, or CQ+PQ for P. vivax infection.

      Phase 1 of the study will monitor the clinical, parasitological, and hematological parameters
      for P. vivax infection over a 42-day follow-up period, which will be used to evaluate drug
      efficacy. Phase 2 will continue monthly follow-up of these patients for one year to assess
      frequency of recurring vivax infections. Results from this research study will be used to
      assist Ethiopia in assessing their current national malaria drug policies.
Following the rapid development of significant drug resistance of Plasmodium falciparum (Pf)
      to chloroquine and then sulfadoxine-pyrimethamine, artemether- lumefantrine (Coartem or AL)
      was adopted as first line therapy in Ethiopia in 2004. According to the current national
      malaria diagnosis and treatment guidelines updated in 2012, first-line treatment for
      uncomplicated P. falciparum infection is AL. First-line treatment for Plasmodium vivax (Pv)
      is chloroquine (CQ) alone in malarious areas and with primaquine in non-malarious areas at
      health center and hospital level. WHO recommends treatment of Pv with CQ or an
      artemisinin-based combination therapy (ACT) in combination with primaquine. For all clinical
      infection without laboratory confirmation, AL is the first-line treatment since AL is
      effective against both Pf and Pv. Thus, in Ethiopia, where treatment for malaria without
      laboratory confirmation occurs frequently, Pv is often treated with AL as the standard of
      care. Similarly, the recommended drug for mixed infection with Pf and Pv is AL. Now with
      wide-spread use of AL and CQ and with evidence that malaria laboratory testing is occurring
      in about half of those suspected with clinical evidence of malaria infection, the
      investigators propose to conduct an antimalarial efficacy study to monitor the effectiveness
      of these therapies in Ethiopia and to determine how efficacious these drugs remain for Pv. In
      addition, with high rates of relapse with P. vivax infection, the efficacy and safety of
      co-administering primaquine will be assessed. This information will inform future policy
      changes with respect to appropriate antimalarial strategies.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: P. vivax treatment failures following treatment with AL compared to AL+PQ
time frame: day 28 and 42
measure: P. vivax treatment failures following treatment with CQ compared to CQ+PQ
time frame: day 28 and 42
measure: Number of episodes of P. vivax parasitemia over one year following initial effective therapy against P. vivax (i.e. parasite clearance)
time frame: 1 year after day 0 of enrollment
measure: Safety endpoint
time frame: baseline (day 0) and day 28
description: Change in hemoglobin concentration
arm group label: Artemether-lumefantrine
arm group type: Active Comparator
description: Weight-based dose to be administered as fixed-dose combination twice daily for three days.
arm group label: Artemether-lumefantrine and primaquine
arm group type: Experimental
description: Artemether-lumefantrine will be given in a weight-based dose to be administered as fixed-dose combination twice daily for three days.
Primaquine will be given beginning on day 2 of artemether-lumefantrine to patients with a normal G6PD test; dose is weight-based to be administered once daily for 14 days.
arm group label: Chloroquine
arm group type: Active Comparator
description: Chloroquine will be given in a weight-based dose to be administered once daily for three days.
arm group label: Chloroquine and primaquine
arm group type: Experimental
description: Chloroquine will be given in a weight-based dose to be administered once daily for three days.
Primaquine will be given beginning on day 2 of chloroquine to patients with a normal G6PD test; dose is weight-based to be administered once daily for 14 days.
intervention type: Drug
intervention name: Artemether-lumefantrine combination
arm group label: Artemether-lumefantrine
arm group label: Artemether-lumefantrine and primaquine
intervention type: Drug
intervention name: Primaquine
arm group label: Artemether-lumefantrine and primaquine
arm group label: Chloroquine and primaquine
intervention type: Drug
intervention name: Chloroquine
arm group label: Chloroquine
arm group label: Chloroquine and primaquine
criteria: 
gender: All
minimum age: 1 Year
maximum age: N/A
healthy volunteers: No
last name: Jimee Hwang, MD MPH
role: Principal Investigator
affiliation: Centers for Disease Control and Prevention
last name: Tesfay Abreha, MSc, MPH
role: Principal Investigator
affiliation: ICAP-Columbia University, Addis Ababa, Ethiopia
last name: David Hoos, MD MPH
role: Principal Investigator
affiliation: ICAP-Columbia University, New York, USA
facility: 
facility: 
country: Ethiopia
responsible party type: Sponsor
mesh term: Infections
mesh term: Malaria
mesh term: Chloroquine
mesh term: Lumefantrine
mesh term: Artemether
mesh term: Primaquine
mesh term: Artemether, Lumefantrine Drug Combination