<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/NCT03307369</url>
  </required_header>
  <id_info>
    <org_study_id>SMRU1706</org_study_id>
    <nct_id>NCT03307369</nct_id>
  </id_info>
  <brief_title>A Retrospective Study of Severe Plasmodium Vivax</brief_title>
  <acronym>SeverePV</acronym>
  <official_title>A Retrospective Study to Assess the Rate of Plasmodium Vivax Infections Presenting With Severe Symptoms From 2001 to 2016 in North-western Thailand</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Oxford</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>
      Historically, Plasmodium vivax has been termed &quot;benign&quot; due to its non-life threatening&#xD;
      clinical course and since the 1800's this view has been cultivated as demonstrated by the use&#xD;
      of the term &quot;benign tertian malaria&quot; to describe the infection.However over the last 15&#xD;
      years, more severe P. vivax malaria is being reported, causing concern that severe P. vivax&#xD;
      malaria is under diagnosed. The definition of severe P. vivax malaria borrows from P.&#xD;
      falciparum and is primarily one of exclusion. Species PCR (polymerase chain reaction) is the&#xD;
      only way to prove P. vivax mono-infection but is expensive and requires skilled staff and&#xD;
      technology. In resource constrained settings, diagnostic testing is not available for&#xD;
      detection of most non-malarial infections further affecting the ability to determine whether&#xD;
      severe symptoms are due to P. vivax malarial infection or a concomitant one.&#xD;
&#xD;
      Retrospective studies from India, Pakistan, Indonesia, Papua New Guinea and Sudan support the&#xD;
      existence of severe P. vivax malaria. However, inconsistent methodologies, definitions of&#xD;
      severity, and use of diagnostic tests to exclude concomitant infection do not allow for&#xD;
      standardised assessments for severe P. vivax infection across studies. A review by Baird,&#xD;
      highlighted that the risk of being classed as suffering from severe illness was only&#xD;
      minimally higher in P. falciparum than in P. vivax, but was unable to combine the data as a&#xD;
      meta-analysis. The primary reported symptoms for severe P. vivax included severe anaemia&#xD;
      particularly in children, severe thrombocytopaenia, respiratory distress, neurological&#xD;
      syndromes (coma or seizures), renal and hepatic failure.&#xD;
&#xD;
      Prospective studies have shown similar results. Tjitra et al showed that 23% (675 of 2,937)&#xD;
      patients admitted with microscopically diagnosed P. vivax infections in Papua, Indonesia had&#xD;
      severe disease and that the risk of severe malaria was significantly higher when admitted&#xD;
      with P. vivax than with P. falciparum. In studies from Papua New Guinea, few differences&#xD;
      between the clinical presentation of P. falciparum and P. vivax were found in children with&#xD;
      severe malaria. This appears to be similar in populations from Sudan, Pakistan and India. In&#xD;
      contrast, in Thailand, anecdotal observations note a low prevalence of severe P. vivax&#xD;
      infections.&#xD;
&#xD;
      The WHO criteria to assess severe P. falciparum have been extrapolated to P. vivax. In the&#xD;
      2015 WHO malaria guidelines some criteria now account for P. vivax, such as removing a&#xD;
      minimum parasitaemia when assessing for severe anaemia. Whilst these criteria may not be the&#xD;
      most sensitive tool to define severe P. vivax infections, it is used for this purpose. It has&#xD;
      been suggested that additional clinical information may be necessary to define truly severe&#xD;
      P. vivax cases.&#xD;
&#xD;
      In order to describe the characteristics of the severity of P. vivax infections in&#xD;
      north-western Thailand, we will perform a retrospective review of annual reports of the&#xD;
      outpatient database, the inpatient database and eligible inpatient medical records from 2001&#xD;
      to 2016. The WHO malaria guidelines and additional clinical information will be used to&#xD;
      assess the severity of infection and thus, a rate of severe P. vivax can be determined.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 27, 2017</start_date>
  <completion_date type="Actual">July 15, 2020</completion_date>
  <primary_completion_date type="Actual">July 15, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The ratio of the number of severe cases determined to be caused by P. vivax to the number of outpatient cases treated for P. vivax</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the age of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the sex of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the medical history of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the parasitaemia of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the duration of hospital stay of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the use of intravenous anti-malarial of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the blood transfusion of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">171</enrollment>
  <condition>Malaria, Vivax</condition>
  <eligibility>
    <study_pop>
      <textblock>
        The retrospective data from approximately 600 P.vivax infected patients who have had&#xD;
        routine clinical work performed in the outpatient and inpatient departments at SMRU during&#xD;
        2001-2016. The patient population consists of refugees and migrants living along the&#xD;
        Thailand Myanmar border in north-western Thailand who seek health care at the SMRU&#xD;
        hospitals.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients voluntarily presented at SMRU clinic during 2001-2016 with a diagnosis of P.&#xD;
             vivax mono-infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients voluntarily presented at SMRU clinic during 2001-2016 with fever and were&#xD;
             seeking consultation for the treatment of malaria or other infections.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shoklo Malaria Research Unit</name>
      <address>
        <city>Mae Sot</city>
        <state>Tak</state>
        <zip>63110</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>October 5, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>August 26, 2020</last_update_submitted>
  <last_update_submitted_qc>August 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Severe malaria</keyword>
  <keyword>plasmodium vivax</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>
  <!-- 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/NCT03307369
org study id: SMRU1706
nct id: NCT03307369
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Historically, Plasmodium vivax has been termed "benign" due to its non-life threatening
      clinical course and since the 1800's this view has been cultivated as demonstrated by the use
      of the term "benign tertian malaria" to describe the infection.However over the last 15
      years, more severe P. vivax malaria is being reported, causing concern that severe P. vivax
      malaria is under diagnosed. The definition of severe P. vivax malaria borrows from P.
      falciparum and is primarily one of exclusion. Species PCR (polymerase chain reaction) is the
      only way to prove P. vivax mono-infection but is expensive and requires skilled staff and
      technology. In resource constrained settings, diagnostic testing is not available for
      detection of most non-malarial infections further affecting the ability to determine whether
      severe symptoms are due to P. vivax malarial infection or a concomitant one.

      Retrospective studies from India, Pakistan, Indonesia, Papua New Guinea and Sudan support the
      existence of severe P. vivax malaria. However, inconsistent methodologies, definitions of
      severity, and use of diagnostic tests to exclude concomitant infection do not allow for
      standardised assessments for severe P. vivax infection across studies. A review by Baird,
      highlighted that the risk of being classed as suffering from severe illness was only
      minimally higher in P. falciparum than in P. vivax, but was unable to combine the data as a
      meta-analysis. The primary reported symptoms for severe P. vivax included severe anaemia
      particularly in children, severe thrombocytopaenia, respiratory distress, neurological
      syndromes (coma or seizures), renal and hepatic failure.

      Prospective studies have shown similar results. Tjitra et al showed that 23% (675 of 2,937)
      patients admitted with microscopically diagnosed P. vivax infections in Papua, Indonesia had
      severe disease and that the risk of severe malaria was significantly higher when admitted
      with P. vivax than with P. falciparum. In studies from Papua New Guinea, few differences
      between the clinical presentation of P. falciparum and P. vivax were found in children with
      severe malaria. This appears to be similar in populations from Sudan, Pakistan and India. In
      contrast, in Thailand, anecdotal observations note a low prevalence of severe P. vivax
      infections.

      The WHO criteria to assess severe P. falciparum have been extrapolated to P. vivax. In the
      2015 WHO malaria guidelines some criteria now account for P. vivax, such as removing a
      minimum parasitaemia when assessing for severe anaemia. Whilst these criteria may not be the
      most sensitive tool to define severe P. vivax infections, it is used for this purpose. It has
      been suggested that additional clinical information may be necessary to define truly severe
      P. vivax cases.

      In order to describe the characteristics of the severity of P. vivax infections in
      north-western Thailand, we will perform a retrospective review of annual reports of the
      outpatient database, the inpatient database and eligible inpatient medical records from 2001
      to 2016. The WHO malaria guidelines and additional clinical information will be used to
      assess the severity of infection and thus, a rate of severe P. vivax can be determined.
observational model: Cohort
time perspective: Retrospective
measure: The ratio of the number of severe cases determined to be caused by P. vivax to the number of outpatient cases treated for P. vivax
time frame: 1 year
measure: Compare the age of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
measure: Compare the sex of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
measure: Compare the medical history of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
measure: Compare the parasitaemia of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
measure: Compare the duration of hospital stay of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
measure: Compare the use of intravenous anti-malarial of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
measure: Compare the blood transfusion of inpatient cases that meet or do not meet the 2015 WHO criteria for severe P. vivax
time frame: 1 year
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: Thailand
responsible party type: Sponsor
mesh term: Malaria
mesh term: Malaria, Vivax