<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/NCT04464291</url>
  </required_header>
  <id_info>
    <org_study_id>IAC-SPECTRUM-2019</org_study_id>
    <nct_id>NCT04464291</nct_id>
  </id_info>
  <brief_title>An Epidemiological Survey to Establish the Spectrum of Circulating Serotypes of S. Pneumoniae, in Patients Older 18 Years</brief_title>
  <acronym>SPECTRUM</acronym>
  <official_title>An Epidemiological Survey to Establish the Spectrum of Circulating Serotypes of S. Pneumoniae, in Patients Older 18 Years: Healthy Carriage, Patients With Non-invasive and Invasive Pneumococcal Infections in the Russian Federation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC)</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>
      Pneumococcal conjugate vaccine was added to the National Immunization Program in Russia in&#xD;
      2014 which could affect the changes in pneumococcal serotypes in growing population. The&#xD;
      purpose of this study is to determine the spectrum of serotypes of S. pneumoniae in patients&#xD;
      older 18-years: in healthy carriage, in patients with non-invasive and invasive forms of&#xD;
      pneumococcal infection. The patients will be divide into several groups: 18-64-years old, 65&#xD;
      years old and older, immunocompromised patients, immunocompetent patients with concomitant&#xD;
      diseases and patients from restricted organized collectives.&#xD;
&#xD;
      This study is designed to meet the following objectives:&#xD;
&#xD;
      To estimate the spectrum of serotypes of S. pneumoniae in adult population in different&#xD;
      regions of Russia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      S. pneumoniae is a major cause of illness and death in children and adults worldwide. It&#xD;
      includes 91 serotypes. The distribution of serotypes that cause disease varies by age,&#xD;
      disease syndrome, disease severity, geographic region, and over time. Infants and young&#xD;
      children are thought to be the main reservoir of this agent. From the colonized&#xD;
      nasopharyngeal mucosa, pneumococci may spread by contiguous, non-invasive extension to other&#xD;
      sites in the respiratory tract.&#xD;
&#xD;
      About 1.6 million cases of fatal pneumococcal disease occur worldwide annually, mostly in&#xD;
      infants and the elderly.3 In addition, immunocompromised individuals of all ages,&#xD;
      immunocompetent patients with concomitant diseases (chronic heart failure,&#xD;
      broncho-obstructive syndrome, liquorrhea, ext.) are at increased risk.&#xD;
&#xD;
      Pneumococcal resistance to commonly used antimicrobials is a serious and increasing problem&#xD;
      worldwide. Therefore vaccination is the most effective mechanism to reduce the incidence of&#xD;
      pneumococcal infection in children and adult patients.&#xD;
&#xD;
      The effectiveness of pneumococcal vaccine is estimated by coverage of serotypes of S.&#xD;
      pneumoniae. The distribution of the serotypes can be potentoinally changed because of the&#xD;
      using of PCV in Russia.&#xD;
&#xD;
      Study design. Prospective Multicentre Microbiological study.&#xD;
&#xD;
      General informed consents are collected from patients at hospital admission. No additional&#xD;
      informed consents will be collected for this study since the procedures of microbiological&#xD;
      sample collection will be performed as a part of standard medical aid practices. Patient&#xD;
      confidentiality will be retained at all times, and patient identifiers will not be included&#xD;
      in the study. Collection of strains will be performed in patients, who meet inclusion&#xD;
      criteria.&#xD;
&#xD;
      Inclusion Criteria&#xD;
&#xD;
        -  Clinically relevant causative isolate - The isolate must meet the laboratory criteria of&#xD;
           S. pneumoniae and be considered the &quot;probable causative agent&quot; of infection.&#xD;
&#xD;
        -  Isolates from patients older 18-years with pneumococcal acute otitis media.&#xD;
&#xD;
        -  Isolates from patients older 18-years with pneumococcal pneumonia&#xD;
&#xD;
        -  Isolates from patients older 18-years with invasive pneumococcal diseases (meningitis,&#xD;
           sepsis)&#xD;
&#xD;
        -  Isolates from healthy carriage older 18-years Exclusion Criteria&#xD;
&#xD;
        -  Isolates that have been collected and/or stored prior to June 1, 2018 or later than&#xD;
           September 30, 2019.&#xD;
&#xD;
        -  Duplicate isolates (same genus and species) obtained at any subsequent time from the&#xD;
           same patient, regardless of susceptibility or phenotypic profile.&#xD;
&#xD;
        -  Environmental samples (non patient-derived) or surveillance cultures taken for infection&#xD;
           control purposes.&#xD;
&#xD;
        -  Outside study group - Any isolate other than those defined by protocol.&#xD;
&#xD;
      Study procedures:&#xD;
&#xD;
        -  collection of strains of S. pneumoniae and identification - the participating laboratory&#xD;
           will collect, identify and store isolates and submit to reference laboratory of the&#xD;
           Institute of Antimicrobial Chemotherapy of Smolensk State Medical University only&#xD;
           clinical isolates that meet the study criteria as defined by protocol. Each isolate must&#xD;
           be accompanied by a Organisms Report Form (ORF). The ORF contains information regarding&#xD;
           the demographics of each isolate. Each investigative site will provide complete isolate&#xD;
           identification using the laboratory's routine procedures.&#xD;
&#xD;
        -  re-identification of strains of S. pneumoniae in the central laboratory (IAC, Smolensk)&#xD;
           - at least, 500 consecutive non-duplicate strains of S. pneumoniae from healthy carriage&#xD;
           and patients with non-invasive and invasive pneumococcal infections will be analyzed in&#xD;
           centers from the following locations: Central region, North-Western region, Ural,&#xD;
           Southern region, Siberia, Far-Eastern region. All the strains will be initially&#xD;
           re-identified to the species level at the IAC laboratory using classic bacteriologic&#xD;
           methods and MALDI Biotyper.&#xD;
&#xD;
        -  susceptibility testing - susceptibility testing to penicillin, erythromycin,&#xD;
           azithromycin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin and vancomycin&#xD;
           will be determined by broth microdilution method. Interpretation will be done according&#xD;
           to EUCAST/CLSI.&#xD;
&#xD;
        -  serotyping (LATEX-TEST, Real-time PCR) - serotyping of S. pneumoniae will be performed&#xD;
           using PNEUMOTEST-LATEX TEST and Real-Time PCR.&#xD;
&#xD;
        -  data analysis&#xD;
&#xD;
        -  reporting Strains collection: 01.06.2019 - 30.01.2020&#xD;
&#xD;
      Laboratory procedures:&#xD;
&#xD;
        1. Re-identification: till 31.10.2019&#xD;
&#xD;
        2. Antimicrobial susceptibility testing: till 01.06.2020&#xD;
&#xD;
        3. Serotyping: till 31.05.2020 Data analysis and reporting: till 28.02.2021 This is a&#xD;
           non-interventional database study based on secondary use of data collected for other&#xD;
           purposes. No administration of any therapeutic or prophylactic agent is required in this&#xD;
           protocol. No reporting of individual adverse events to regulatory agencies is planned&#xD;
           for this database study because there is no access to individual patient/subject records&#xD;
           and it is not possible to assess the causality of individual cases. Pre-specified health&#xD;
           outcomes of interest, including any that qualify as adverse events, will be summarized&#xD;
           as part of any interim analysis (including safety analysis, if required) and in the&#xD;
           final study report, which will be provided to regulatory agencies by the sponsor as&#xD;
           required.&#xD;
&#xD;
      Any relevant safety information will be summarized in the appropriate Periodic Safety Update&#xD;
      Report (PSUR)/Periodic Benefit Risk Evaluation Report (PBRER) and/or Development Safety&#xD;
      Update Reports (DSUR) if required.&#xD;
&#xD;
      If an investigator elects to spontaneously report any suspected adverse reactions, they&#xD;
      should be reported via fax to Merck AER Mailbox FAX #215-661-6229 (US), or toll-free fax&#xD;
      1-800-547-5552 (ex-US and US availability), in English using an AE form (attached) for&#xD;
      reporting to worldwide regulatory agencies as appropriate&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Actual">January 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 1, 2020</primary_completion_date>
  <phase>N/A</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>Prospective Multicentre Microbiological study</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of pneumococcal infection in the Russian Federation, caused by different serotypes of Streptococcus pneumoniae</measure>
    <time_frame>1 year</time_frame>
    <description>The incidence will be detected with descriptive statistics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of antimicrobial resistance of serotypes of Streptococcus pneumoniae</measure>
    <time_frame>1 year</time_frame>
    <description>Detection of antimicrobial resistance to penicillin, erythromycin, azithromycin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin and vancomycin will be detected with descriptive statistics</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">500</enrollment>
  <condition>Pneumonia, Pneumococcal</condition>
  <condition>Invasive Pneumococcal Disease</condition>
  <condition>Acute Otitis Media</condition>
  <arm_group>
    <arm_group_label>Patients with pneumococcal infection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>There will be assessing the prevalence of Streptococcus pneumoniae serotypes in the nasopharynx in healthy people; in middle ear liquid in patients with acute otitis media; in sputum and epithelial lining fluid in patients with community-acquired pneumonia; in spinal fluid in patients with invasive pneumococcal indection</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Detection of Streptococcus pneumoniae strains</intervention_name>
    <description>There will be detection of Streptococcus pneumoniae, serotype identification, susceptibility tests for penicillin, erythromycin, azithromycin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin and vancomycin</description>
    <arm_group_label>Patients with pneumococcal infection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinically relevant causative isolate - The isolate must meet the laboratory criteria&#xD;
             of S. pneumoniae and be considered the &quot;probable causative agent&quot; of infection.&#xD;
&#xD;
          2. Isolates from patients older 18-years with pneumococcal acute otitis media&#xD;
&#xD;
          3. Isolates from patients older 18-years with pneumococcal pneumonia&#xD;
&#xD;
          4. Isolates from patients older 18-years with invasive pneumococcal diseases (meningitis,&#xD;
             sepsis)&#xD;
&#xD;
          5. Isolates from healthy carriage older 18-years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Isolates that have been collected and/or stored prior to June 1, 2018 or later than&#xD;
             September 30, 2019.&#xD;
&#xD;
          2. Duplicate isolates (same genus and species) obtained at any subsequent time from the&#xD;
             same patient, regardless of susceptibility or phenotypic profile.&#xD;
&#xD;
          3. Environmental samples (non patient-derived) or surveillance cultures taken for&#xD;
             infection control purposes.&#xD;
&#xD;
          4. Outside study group - Any isolate other than those defined by the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy</name>
      <address>
        <city>Smolensk</city>
        <zip>214019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>September 9, 2019</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>February 8, 2021</last_update_submitted>
  <last_update_submitted_qc>February 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC)</investigator_affiliation>
    <investigator_full_name>Roman Kozlov</investigator_full_name>
    <investigator_title>President</investigator_title>
  </responsible_party>
  <keyword>Serotype</keyword>
  <keyword>Streptococcus pneumoniae</keyword>
  <keyword>Epidemiology</keyword>
  <keyword>Antmicrobial resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumococcal Infections</mesh_term>
    <mesh_term>Pneumonia, Pneumococcal</mesh_term>
    <mesh_term>Otitis Media</mesh_term>
  </condition_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/NCT04464291
org study id: IAC-SPECTRUM-2019
nct id: NCT04464291
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pneumococcal conjugate vaccine was added to the National Immunization Program in Russia in
      2014 which could affect the changes in pneumococcal serotypes in growing population. The
      purpose of this study is to determine the spectrum of serotypes of S. pneumoniae in patients
      older 18-years: in healthy carriage, in patients with non-invasive and invasive forms of
      pneumococcal infection. The patients will be divide into several groups: 18-64-years old, 65
      years old and older, immunocompromised patients, immunocompetent patients with concomitant
      diseases and patients from restricted organized collectives.

      This study is designed to meet the following objectives:

      To estimate the spectrum of serotypes of S. pneumoniae in adult population in different
      regions of Russia.
S. pneumoniae is a major cause of illness and death in children and adults worldwide. It
      includes 91 serotypes. The distribution of serotypes that cause disease varies by age,
      disease syndrome, disease severity, geographic region, and over time. Infants and young
      children are thought to be the main reservoir of this agent. From the colonized
      nasopharyngeal mucosa, pneumococci may spread by contiguous, non-invasive extension to other
      sites in the respiratory tract.

      About 1.6 million cases of fatal pneumococcal disease occur worldwide annually, mostly in
      infants and the elderly.3 In addition, immunocompromised individuals of all ages,
      immunocompetent patients with concomitant diseases (chronic heart failure,
      broncho-obstructive syndrome, liquorrhea, ext.) are at increased risk.

      Pneumococcal resistance to commonly used antimicrobials is a serious and increasing problem
      worldwide. Therefore vaccination is the most effective mechanism to reduce the incidence of
      pneumococcal infection in children and adult patients.

      The effectiveness of pneumococcal vaccine is estimated by coverage of serotypes of S.
      pneumoniae. The distribution of the serotypes can be potentoinally changed because of the
      using of PCV in Russia.

      Study design. Prospective Multicentre Microbiological study.

      General informed consents are collected from patients at hospital admission. No additional
      informed consents will be collected for this study since the procedures of microbiological
      sample collection will be performed as a part of standard medical aid practices. Patient
      confidentiality will be retained at all times, and patient identifiers will not be included
      in the study. Collection of strains will be performed in patients, who meet inclusion
      criteria.

      Inclusion Criteria

        -  Clinically relevant causative isolate - The isolate must meet the laboratory criteria of
           S. pneumoniae and be considered the "probable causative agent" of infection.

        -  Isolates from patients older 18-years with pneumococcal acute otitis media.

        -  Isolates from patients older 18-years with pneumococcal pneumonia

        -  Isolates from patients older 18-years with invasive pneumococcal diseases (meningitis,
           sepsis)

        -  Isolates from healthy carriage older 18-years Exclusion Criteria

        -  Isolates that have been collected and/or stored prior to June 1, 2018 or later than
           September 30, 2019.

        -  Duplicate isolates (same genus and species) obtained at any subsequent time from the
           same patient, regardless of susceptibility or phenotypic profile.

        -  Environmental samples (non patient-derived) or surveillance cultures taken for infection
           control purposes.

        -  Outside study group - Any isolate other than those defined by protocol.

      Study procedures:

        -  collection of strains of S. pneumoniae and identification - the participating laboratory
           will collect, identify and store isolates and submit to reference laboratory of the
           Institute of Antimicrobial Chemotherapy of Smolensk State Medical University only
           clinical isolates that meet the study criteria as defined by protocol. Each isolate must
           be accompanied by a Organisms Report Form (ORF). The ORF contains information regarding
           the demographics of each isolate. Each investigative site will provide complete isolate
           identification using the laboratory's routine procedures.

        -  re-identification of strains of S. pneumoniae in the central laboratory (IAC, Smolensk)
           - at least, 500 consecutive non-duplicate strains of S. pneumoniae from healthy carriage
           and patients with non-invasive and invasive pneumococcal infections will be analyzed in
           centers from the following locations: Central region, North-Western region, Ural,
           Southern region, Siberia, Far-Eastern region. All the strains will be initially
           re-identified to the species level at the IAC laboratory using classic bacteriologic
           methods and MALDI Biotyper.

        -  susceptibility testing - susceptibility testing to penicillin, erythromycin,
           azithromycin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin and vancomycin
           will be determined by broth microdilution method. Interpretation will be done according
           to EUCAST/CLSI.

        -  serotyping (LATEX-TEST, Real-time PCR) - serotyping of S. pneumoniae will be performed
           using PNEUMOTEST-LATEX TEST and Real-Time PCR.

        -  data analysis

        -  reporting Strains collection: 01.06.2019 - 30.01.2020

      Laboratory procedures:

        1. Re-identification: till 31.10.2019

        2. Antimicrobial susceptibility testing: till 01.06.2020

        3. Serotyping: till 31.05.2020 Data analysis and reporting: till 28.02.2021 This is a
           non-interventional database study based on secondary use of data collected for other
           purposes. No administration of any therapeutic or prophylactic agent is required in this
           protocol. No reporting of individual adverse events to regulatory agencies is planned
           for this database study because there is no access to individual patient/subject records
           and it is not possible to assess the causality of individual cases. Pre-specified health
           outcomes of interest, including any that qualify as adverse events, will be summarized
           as part of any interim analysis (including safety analysis, if required) and in the
           final study report, which will be provided to regulatory agencies by the sponsor as
           required.

      Any relevant safety information will be summarized in the appropriate Periodic Safety Update
      Report (PSUR)/Periodic Benefit Risk Evaluation Report (PBRER) and/or Development Safety
      Update Reports (DSUR) if required.

      If an investigator elects to spontaneously report any suspected adverse reactions, they
      should be reported via fax to Merck AER Mailbox FAX #215-661-6229 (US), or toll-free fax
      1-800-547-5552 (ex-US and US availability), in English using an AE form (attached) for
      reporting to worldwide regulatory agencies as appropriate
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective Multicentre Microbiological study
primary purpose: Screening
masking: None (Open Label)
measure: Incidence of pneumococcal infection in the Russian Federation, caused by different serotypes of Streptococcus pneumoniae
time frame: 1 year
description: The incidence will be detected with descriptive statistics
measure: Incidence of antimicrobial resistance of serotypes of Streptococcus pneumoniae
time frame: 1 year
description: Detection of antimicrobial resistance to penicillin, erythromycin, azithromycin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin and vancomycin will be detected with descriptive statistics
arm group label: Patients with pneumococcal infection
arm group type: Experimental
description: There will be assessing the prevalence of Streptococcus pneumoniae serotypes in the nasopharynx in healthy people; in middle ear liquid in patients with acute otitis media; in sputum and epithelial lining fluid in patients with community-acquired pneumonia; in spinal fluid in patients with invasive pneumococcal indection
intervention type: Other
intervention name: Detection of Streptococcus pneumoniae strains
description: There will be detection of Streptococcus pneumoniae, serotype identification, susceptibility tests for penicillin, erythromycin, azithromycin, tetracycline, ciprofloxacin, levofloxacin, moxifloxacin and vancomycin
arm group label: Patients with pneumococcal infection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
country: Russian Federation
responsible party type: Principal Investigator
investigator affiliation: The Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC)
investigator full name: Roman Kozlov
investigator title: President
mesh term: Pneumonia
mesh term: Pneumococcal Infections
mesh term: Pneumonia, Pneumococcal
mesh term: Otitis Media
sharing ipd: No