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/NCT05979896</url>
    </required_header>
    <id_info>
      <org_study_id>SMCNGPHASE1</org_study_id>
      <nct_id>NCT05979896</nct_id>
    </id_info>
    <brief_title>Chemoprevention Efficacy Study Nigeria</brief_title>
    <official_title>A Study Protocol to Assess the Chemoprevention Efficacy of Sulphadoxine-Pyrimethamine Plus Amodiaquine (SPAQ) and Resistance Marker Prevalence in Children 3-59 Months in Sokoto and Kwara States, Nigeria.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Malaria Consortium</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Malaria Consortium</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 study aims to assess the chemoprevention efficacy of Sulfadoxine-Pyrimethamine and&#xD;
        Amodiaquine (SPAQ) used in standard age-based dosing regimens used in Seasonal Malaria&#xD;
        Chemoprevention (SMC) and SPAQ resistance marker prevalences and assocations among children 3&#xD;
        - 59 months in Sokoto and Kwara States, Nigeria.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study aims (1) to determine the chemoprevention efficacy of Sulfadoxine-Pyrimethamine and&#xD;
        Amodiaquine (SPAQ) used in standard age-based dosing regimens for Seasonal Malaria&#xD;
        Chemoprevention (SMC) in children 3-59 months and (2) determine the prevalences and&#xD;
        associations of drug resistance genotypes associated with resistance to SPAQ.&#xD;
  &#xD;
          1. a prospective cohort study to determine the chemoprevention efficacy of SPAQ (if SPAQ&#xD;
             provides 28 days of protection from Plasmodium falciparum (P. falciparum) malaria&#xD;
             infection by clearing existing and preventing new infections) and whether drug&#xD;
             concentrations and/or resistance influence the ability to clear and prevent these P.&#xD;
             falciparum infections.&#xD;
  &#xD;
          2. a resistance markers study in symptomatic RDT positive children 3-59 months to measure&#xD;
             sulfadoxine-pyrimethamine and amodiaquine resistance marker prevalence and association.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 28, 2023</start_date>
    <completion_date type="Anticipated">May 15, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 15, 2023</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Cohort</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Chemoprevention failure as defined by qPCR positive parasites or malaria slide positive parasites</measure>
      <time_frame>28 days</time_frame>
      <description>Malaria slides and dry blood spots (DBS) taken at days 0,7,14, 21, 28 of a one month drug administration cycle will be analysed to detect parasitemia in children treated with SPAQ. Chemoprevention failure has occured if a malaria slide is positive for parasites 7 days or more after drug administration or if a qPCR detects low level parasitemia at the end of the administration cycle (one month).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Prevalence of antimalarial resistance markers among chemoprevention failures (as defined in outcome 1)</measure>
      <time_frame>28 days</time_frame>
      <description>All Dried blood spots (DBS) will be analysed for malaria mutation genotypes (dhfr, dhps, Pfcrt, pfmdr1) on baseline and endline and additionally throughout the cycle if a chemoprevention failure (as defined in outcome 1) has occured.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Drug concentrations of Sulfadoxine-pyrimethamine and amodiaquine among chemoprevention failures (as defined in outcome 1)</measure>
      <time_frame>28 days</time_frame>
      <description>Drug concentrations of SPAQ will be analyzed on all samples (taken at days 7,14,21,28 throughout the one month cycle) in order to be linked to chemoprevention failures as defined in outcome 1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Prevalence over time of parasites with dhfr/dhps/pfcrt/pfmdr1 mutations in symptomatic children with a positive diagnostic test residing in districts where SMC is implemented</measure>
      <time_frame>28 days preceding implementation of chemoprevention efficacy study component</time_frame>
      <description>The outcome measure to meet the secondary objective is the prevalence of molecular markers associated with SP (codons 108, 51 and 59 in dhfr and 437, 540 and 581 in dhps) and amodiaquine (codons 72-76 Pfcrt and 86, 184 and 1246 pfmdr1), as well as other markers of parasite genetic diversity, in blood samples collected from symptomatic children under five years with a positive RDT attending selected health facilities in areas with SMC</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">800</enrollment>
    <condition>Malaria</condition>
    <arm_group>
      <arm_group_label>Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Children aged 3-59 months will receive directly observed therapy of standard aged based dosing of Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ) over 3 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Standard age based SPAQ administration for SMC</intervention_name>
      <description>Sulfadoxine-pyrimethamine and amodiaquine (SPAQ) is administered in standard WHO approved age based regimens as used in Seasonal Malaria Chemoprevention Programmes.&#xD;
  Sulphadoxine is a slowly eliminated sulphonamide. It is used in a fixed dose combination of 20 parts sulphadoxine with 1 part pyrimethamine given orally or intramuscularly.&#xD;
  Sulphadoxine is readily absorbed from the GIT. It is widely distributed in body tissues and fluids and crosses the placenta into foetal circulation. It is also readily detectable in breast milk. It is excreted predominantly as the unchanged drug. AQ Amodiaquine is a Mannich base 4 amino-quinoline that interferes with parasite haem detoxification. It is more effective than chloroquine in both chloroquine sensitive and resistant P. falciparum infections. However, there is cross-resistance between chloroquine and amodiaquine.&#xD;
  It is readily absorbed in the GIT and rapidly converted in the liver to the active metabolite, desethylamodiaquine.</description>
      <arm_group_label>Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria&#xD;
  &#xD;
            -  Children between 3-59 months.&#xD;
  &#xD;
            -  Being resident in the research study area.&#xD;
  &#xD;
            -  Afebrile children with no other malaria associated symptoms in the past 48 hours or at&#xD;
               time of recruitment.&#xD;
  &#xD;
            -  Consent to participate in the study obtained.&#xD;
  &#xD;
            -  Can comply with 3 days DOT of standard SPAQ regimen.&#xD;
  &#xD;
            -  Willingness and ability of the child's guardians to comply with the study protocol for&#xD;
               the duration of the study including all dry blood spot and slide collections.&#xD;
  &#xD;
          Exclusion criteria&#xD;
  &#xD;
            -  Symptoms of malaria (tympanic fever ≥ 37.5 °C or history of fever in past 48 hours)&#xD;
  &#xD;
            -  Known allergy to SPAQ.&#xD;
  &#xD;
            -  Receiving a sulfa-based medication for treatment or prophylaxis, including&#xD;
               co-trimoxazole (trimethoprim-sulfamethoxazole).&#xD;
  &#xD;
            -  Individuals receiving azithromycin due to the antimalarial activity of azithromycin.&#xD;
  &#xD;
            -  Severe malnutrition according to WHO guidelines&#xD;
  &#xD;
            -  HIV positive or ARV use (SPAQ MUST NEVER be used with children taking the&#xD;
               antiretroviral efavirenz)&#xD;
  &#xD;
            -  Chronic illness of any kind.&#xD;
  &#xD;
            -  Treatment with an ACT in previous 2 weeks.&#xD;
  &#xD;
            -  Previous treatment with SPAQ this malaria season.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>3 Months</minimum_age>
      <maximum_age>59 Months</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Craig Bonnington</last_name>
      <role>Principal Investigator</role>
      <affiliation>Malaria Consortium</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Craig Bonnington</last_name>
      <phone>+447597549279</phone>
      <email>C.BONNINGTON@MALARIACONSORTIUM.ORG</email>
    </overall_contact>
    <location>
      <facility>
        <name>Kwara Sentinell Site</name>
        <address>
          <city>Kwara</city>
          <country>Nigeria</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Mohammed Abdulkadir</last_name>
      </contact>
      <contact_backup>
        <phone>+2348065754333</phone>
        <email>docmohng@gmail.com</email>
      </contact_backup>
      <investigator>
        <last_name>Mohammed Abdulkadir, Dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Nigeria</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Seasonal Malaria Chemoprevention</keyword>
    <keyword>Chemoprevention efficacy</keyword>
    <keyword>Antimalarial drug resistance</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Malaria</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</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/NCT05979896
  org study id: SMCNGPHASE1
  nct id: NCT05979896
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The study aims to assess the chemoprevention efficacy of Sulfadoxine-Pyrimethamine and
        Amodiaquine (SPAQ) used in standard age-based dosing regimens used in Seasonal Malaria
        Chemoprevention (SMC) and SPAQ resistance marker prevalences and assocations among children 3
        - 59 months in Sokoto and Kwara States, Nigeria.
  The study aims (1) to determine the chemoprevention efficacy of Sulfadoxine-Pyrimethamine and
        Amodiaquine (SPAQ) used in standard age-based dosing regimens for Seasonal Malaria
        Chemoprevention (SMC) in children 3-59 months and (2) determine the prevalences and
        associations of drug resistance genotypes associated with resistance to SPAQ.
  
          1. a prospective cohort study to determine the chemoprevention efficacy of SPAQ (if SPAQ
             provides 28 days of protection from Plasmodium falciparum (P. falciparum) malaria
             infection by clearing existing and preventing new infections) and whether drug
             concentrations and/or resistance influence the ability to clear and prevent these P.
             falciparum infections.
  
          2. a resistance markers study in symptomatic RDT positive children 3-59 months to measure
             sulfadoxine-pyrimethamine and amodiaquine resistance marker prevalence and association.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Cohort
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Chemoprevention failure as defined by qPCR positive parasites or malaria slide positive parasites
  time frame: 28 days
  description: Malaria slides and dry blood spots (DBS) taken at days 0,7,14, 21, 28 of a one month drug administration cycle will be analysed to detect parasitemia in children treated with SPAQ. Chemoprevention failure has occured if a malaria slide is positive for parasites 7 days or more after drug administration or if a qPCR detects low level parasitemia at the end of the administration cycle (one month).
  measure: Prevalence of antimalarial resistance markers among chemoprevention failures (as defined in outcome 1)
  time frame: 28 days
  description: All Dried blood spots (DBS) will be analysed for malaria mutation genotypes (dhfr, dhps, Pfcrt, pfmdr1) on baseline and endline and additionally throughout the cycle if a chemoprevention failure (as defined in outcome 1) has occured.
  measure: Drug concentrations of Sulfadoxine-pyrimethamine and amodiaquine among chemoprevention failures (as defined in outcome 1)
  time frame: 28 days
  description: Drug concentrations of SPAQ will be analyzed on all samples (taken at days 7,14,21,28 throughout the one month cycle) in order to be linked to chemoprevention failures as defined in outcome 1.
  measure: Prevalence over time of parasites with dhfr/dhps/pfcrt/pfmdr1 mutations in symptomatic children with a positive diagnostic test residing in districts where SMC is implemented
  time frame: 28 days preceding implementation of chemoprevention efficacy study component
  description: The outcome measure to meet the secondary objective is the prevalence of molecular markers associated with SP (codons 108, 51 and 59 in dhfr and 437, 540 and 581 in dhps) and amodiaquine (codons 72-76 Pfcrt and 86, 184 and 1246 pfmdr1), as well as other markers of parasite genetic diversity, in blood samples collected from symptomatic children under five years with a positive RDT attending selected health facilities in areas with SMC
  arm group label: Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)
  arm group type: Experimental
  description: Children aged 3-59 months will receive directly observed therapy of standard aged based dosing of Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ) over 3 days.
  intervention type: Drug
  intervention name: Standard age based SPAQ administration for SMC
  description: Sulfadoxine-pyrimethamine and amodiaquine (SPAQ) is administered in standard WHO approved age based regimens as used in Seasonal Malaria Chemoprevention Programmes.
  Sulphadoxine is a slowly eliminated sulphonamide. It is used in a fixed dose combination of 20 parts sulphadoxine with 1 part pyrimethamine given orally or intramuscularly.
  Sulphadoxine is readily absorbed from the GIT. It is widely distributed in body tissues and fluids and crosses the placenta into foetal circulation. It is also readily detectable in breast milk. It is excreted predominantly as the unchanged drug. AQ Amodiaquine is a Mannich base 4 amino-quinoline that interferes with parasite haem detoxification. It is more effective than chloroquine in both chloroquine sensitive and resistant P. falciparum infections. However, there is cross-resistance between chloroquine and amodiaquine.
  It is readily absorbed in the GIT and rapidly converted in the liver to the active metabolite, desethylamodiaquine.
  arm group label: Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)
  criteria: 
  gender: All
  minimum age: 3 Months
  maximum age: 59 Months
  healthy volunteers: Accepts Healthy Volunteers
  last name: Craig Bonnington
  role: Principal Investigator
  affiliation: Malaria Consortium
  last name: Craig Bonnington
  phone: +447597549279
  email: C.BONNINGTON@MALARIACONSORTIUM.ORG
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: Nigeria
  responsible party type: Sponsor
  mesh term: Malaria
  sharing ipd: No