<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/NCT03039699</url>
  </required_header>
  <id_info>
    <org_study_id>MMH-ER-008</org_study_id>
    <nct_id>NCT03039699</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Viral Intestinal Infections in Children</brief_title>
  <official_title>International Multicenter, Double-blind, Randomized, Parallel Group Placebo-Controlled Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Viral Intestinal Infections in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Materia Medica Holding</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Materia Medica Holding</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to obtain additional data on efficacy and safety of Ergoferon in&#xD;
      the treatment of viral intestinal infections in inpatient children.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design: a multicenter, double-blind, placebo-controlled, randomized clinical trial in&#xD;
      parallel groups.&#xD;
&#xD;
      This study will enroll subjects of both sexes aged from 6 months to 6 years who are admitted&#xD;
      to hospital within 48 h of the onset of acute intestinal infection (AII), presumably of viral&#xD;
      aetiology. Patients to be enrolled in the screening will be children with typical viral&#xD;
      gastroenteritis/enteritis symptoms. The key symptom is decreased in the consistency of stools&#xD;
      (loose or liquid) and increased in the frequency of its evacuations (at list 3 time daily).&#xD;
      Virus detection in stool samples will be performed by polymerase chain reaction (PCR).&#xD;
&#xD;
      After the parent/adopter signs a parents/adopters information sheet (Informed Consent form)&#xD;
      for the child's participation in the clinical trial, the recording of medical history data, a&#xD;
      medical examination including the evaluation of symptoms on the Clinical Dehydration Scale&#xD;
      (CDS) by pediatrician, and laboratory tests will be performed during Visit 1 (Day 1). If&#xD;
      inclusion criteria are met and non-inclusion criteria are absent (day 1), the patient will be&#xD;
      included in the trial and randomized to administer either Ergoferon or Placebo.&#xD;
&#xD;
      In addition to the standard/pathogenetic therapies, group 1 patients will take Ergoferon&#xD;
      following a 5-day regimen, whereas group 2 patients will receive Placebo. The&#xD;
      parents/adopters of the patient will be provided with a patient diary and instructed how to&#xD;
      complete the diary.&#xD;
&#xD;
      Before treatment stool specimens will be collected from the patients for detection and&#xD;
      differentiation of Rotavirus A, Norovirus 2 genotype, Astrovirus, Adenovirus F, Shigella&#xD;
      spp., enteroinvasive E.coli (EIEC), Salmonella spp., and thermophilic Campylobacter spp.&#xD;
      using a PCR assay to diagnose the etiology of intestinal infection. In total, the patients&#xD;
      will be monitored for 10 days (screening, randomization, treatment initiation - Day 1; the&#xD;
      treatment on Days 1-5; observation in hospital - Day 6, and follow-up period - Day 7-10).&#xD;
      During the treatment and inpatient observation periods (Days 1-6, Visits 1-6), the patients&#xD;
      will be examined daily by a pediatrician, and the examination results, including the CDS&#xD;
      scores, will be recorded in source documents. The patient's parent/adopter will complete the&#xD;
      patient diary every day, recording the presence/absence of diarrhea signs, vomiting, and body&#xD;
      temperature. The pediatrician will check them each time for the correctness of completion. On&#xD;
      day 10 (after hospital discharge), Visit 7 will be done (as an in-person visit (a hospital or&#xD;
      calling a doctor) or a distance, 'phone' visit) to interview the parents/adopters about the&#xD;
      patient's health, presence of any complications, and use of medications (the pediatrician&#xD;
      will use this information to complete a questionnaire). Collection of stool specimens and&#xD;
      repeat PCR for Rotaviruses/Noroviruses/Astroviruses/Adenoviruses, Shigella spp., EIEC,&#xD;
      Salmonella spp., and Campylobacter spp. will be performed on Days 3, 4, and 6 of inpatient&#xD;
      observation and after discharge from the hospital (Day 10); collection of blood and urine&#xD;
      specimens for safety tests will be carried out at baseline and before hospital discharge (day&#xD;
      6). The recording of the intake of study therapies and of concomitant medications as well as&#xD;
      the assessment of compliance with and safety of the study therapies will be performed on Days&#xD;
      2-6 and 10.&#xD;
&#xD;
      Patients who recovered while in hospital and are discharged from the unit earlier than at 5&#xD;
      days will undergo the procedures of Visit 6, including the collection of biological specimens&#xD;
      for PCR (efficacy evaluation) and biochemistry, blood test and urinalysis (safety&#xD;
      assessment). The parents/adopters will be given the blister pack with the remaining study&#xD;
      drug so that the patient can continue the treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 23, 2016</start_date>
  <completion_date type="Actual">June 1, 2019</completion_date>
  <primary_completion_date type="Actual">June 1, 2019</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Average Diarrhea Duration.</measure>
    <time_frame>On days 1-10 of observation period.</time_frame>
    <description>Diarrhea duration is considered as the time between receiving the first dose of investigational medicine /placebo and the normal consistency of stool pattern (to the previous stool consistency before diarrhea), i.e.&#xD;
time to the first loose stool which is followed by two normal consistency stools over 24 h (infants may have three episodes of loose stool over a 24-hour period), or&#xD;
time to ≤3 episodes of stool occurring over 24 h, at least 2 of which are normal consistency stools, or&#xD;
time to the absence of stools for ≥12 h which is not followed by new episodes of diarrhea (total stool frequency over 24 h - less than 3 times).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Without Diarrhea.</measure>
    <time_frame>48, 72 and 96 hours of the treatment.</time_frame>
    <description>Based on medical records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Recovery.</measure>
    <time_frame>48, 72 and 96 hours of the treatment.</time_frame>
    <description>Based on medical records. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Illness Duration.</measure>
    <time_frame>On days 1-10 of observation period.</time_frame>
    <description>From the enrollment to the recovery. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Clinical Dehydration Scale Score.</measure>
    <time_frame>24, 48, and 72 hours of the treatment.</time_frame>
    <description>Based on medical records. Clinical Dehydration Scale score is more or equal 1. Note: minimum values - 0 points, maximum values - 8 points. Interpretation: 0 points - no dehydration, from 1 to 4 points - light dehydration, 5-8 points - average/severe dehydration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Vomiting Duration (if Any).</measure>
    <time_frame>On days 1-10 of observation period.</time_frame>
    <description>Based on medical records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Negative PCR Tests.</measure>
    <time_frame>On days 3, 4, 6 and 10 of observation period.</time_frame>
    <description>Based on medical records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Worsening of Illness and/or Hospital-acquired Infection.</measure>
    <time_frame>On days 1-10 of observation period.</time_frame>
    <description>Based on medical records. Worsening of illness: an increase in dehydration scores and worsening of non-specific symptoms, as evidenced by a decline in general appearance, increasing fatigue and drowsiness, refusal to eat and drink, severe tachycardia/bradycardia, unstable hemodynamics, tachypnea, hypo- or hyperventilation, circulation disorders, peripheral cyanosis, sunken eyes, severe dryness of skin and mucous/tongue, poor tissue turgor, absent tears, persistent vomiting, anuria/acute kidney injury, seizure/convulsions, and meningismus. Hospital-acquired infection: a viral or bacterial infection (intestinal, respiratory or urinary tract infection, etc.) occurring after at least 48 h of hospital stay and confirmed by laboratory tests.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">259</enrollment>
  <condition>Viral Intestinal Infection</condition>
  <arm_group>
    <arm_group_label>Ergoferon</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet for oral use. Dose per administration - 1 tablet per intake (outside a meal/feeding). Within the first 2 hours - 1 tablet every 30 minutes, followed by 3 more tablets at time intervals equally separated throughout the rest of the day; from day 2 to day 5 - 1 tablet 3 times daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Tablet for oral use. Dose per administration - 1 tablet per intake (outside a meal/feeding). Within the first 2 hours - 1 tablet every 30 minutes, followed by 3 more tablets at time intervals equally separated throughout the rest of the day; from day 2 to day 5 - 1 tablet 3 times daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ergoferon</intervention_name>
    <arm_group_label>Ergoferon</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients of both gender aged from 6 months to 6 years, who have been admitted to&#xD;
             infectious diseases unit.&#xD;
&#xD;
          2. Diarrhea (watery diarrhea at least 3 times a day).&#xD;
&#xD;
          3. CDS score of ≥1.&#xD;
&#xD;
          4. The first 48 hours from the onset of the first diarrhea episode.&#xD;
&#xD;
          5. Start of study treatment (Ergoferon/Placebo) within 12 hours after the start of the&#xD;
             standard hospital therapy.&#xD;
&#xD;
          6. Availability of a patient information sheet (Informed Consent form) signed by the&#xD;
             patient's parents/adopters to confirm the child's participation in the clinical trial&#xD;
             signed by one parent/adopter of the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Suspected bacterial intestinal infection.&#xD;
&#xD;
          2. Suspected infectious diseases affecting other organ systems (e.g. pneumonia,&#xD;
             meningitis, sepsis, otitis media, urinary tract infection, etc.).&#xD;
&#xD;
          3. Severe intestinal infection.&#xD;
&#xD;
          4. Severe dehydration (CDS score ≥7).&#xD;
&#xD;
          5. Anuria (acute kidney injury).&#xD;
&#xD;
          6. Medical history or prior diagnosis of serious diseases, including primary/secondary&#xD;
             immunodeficiency, oncological disease, diabetes mellitus, infantile cerebral palsy,&#xD;
             mucoviscidosis/cystic fibrosis etc.&#xD;
&#xD;
          7. Exacerbation, or decompensation of chronic disease, including diseases of the&#xD;
             digestive system that would affect the patient's ability to participate in the&#xD;
             clinical trial.&#xD;
&#xD;
          8. Malabsorption syndrome, including congenital or acquired lactose intolerance/lactase&#xD;
             deficiency or any other disaccharidase deficiency and galactosemia.&#xD;
&#xD;
          9. Allergy/ intolerance to any of the components of medications used in the treatment.&#xD;
&#xD;
         10. Course intake of medicines listed in the section &quot;Prohibited concomitant treatment&quot;&#xD;
             for 2 weeks prior to the enrollment in the trial.&#xD;
&#xD;
         11. Participation in other clinical trials within 3 months prior to the enrollment in this&#xD;
             study.&#xD;
&#xD;
         12. Patients whose parents/adopters, from the investigator's point of view, will fail to&#xD;
             comply with the observation requirements of the trial or with the dosing regimen of&#xD;
             the study drugs.&#xD;
&#xD;
         13. Patient's parents/adopters are related to the research staff of the clinical&#xD;
             investigative site who are directly involved in the trial or are the immediate family&#xD;
             member of the researcher. The immediate family members include husband/wife, parents,&#xD;
             children or brothers (or sisters), regardless of whether they are natural or adopted.&#xD;
&#xD;
         14. The patient's parent/adopter works for MATERIA MEDICA HOLDING (i.e., is the company's&#xD;
             employee, temporary contract worker or appointed official responsible for carrying out&#xD;
             the research) or the immediate relative.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>6 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>State budgetary Health Care institution of the Arkhangelsk region &quot;Arkhangelsk Regional Pediatric Clinical Hospital named after PG Vyzhletsova&quot;</name>
      <address>
        <city>Arkhangel'sk</city>
        <zip>163002</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Institution of Higher Professional Education &quot;Urals State Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620028</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Kazan Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Kazan'</city>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal Budget Institution of Science &quot;Central Research Institute of Epidemiology&quot; of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance</name>
      <address>
        <city>Moscow</city>
        <zip>111123</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pirogov Russian National Research Medical University</name>
      <address>
        <city>Moscow</city>
        <zip>117997</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Orenburg State Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Orenburg</city>
        <zip>460000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Budgetary Health Care Institution &quot;Semashko City Hospital №1 Rostov-on-Don &quot;</name>
      <address>
        <city>Rostov-on-Don</city>
        <zip>344000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Saint Petersburg State Pediatric Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>194100</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sailnt Petersburg State Budgetary Health Care Institution &quot;City Child Hospital №22&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>196657</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Institution &quot;Scientific Research Institute of Children's Infections Federal Biomedical Agency&quot;</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The State Budget Educational institution of High Professional Training Smolensk State Medical University of Ministry of Health Care of the Russian Federation</name>
      <address>
        <city>Smolensk</city>
        <zip>214018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Budgetary Educational Institution of Higher Education &quot;Yaroslavl State Medical University&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientific Research Institute of Virology of Ministry of Health of Republic Uzbekistan</name>
      <address>
        <city>Tashkent</city>
        <zip>100194</zip>
        <country>Uzbekistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
    <country>Uzbekistan</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <results_first_submitted>August 27, 2020</results_first_submitted>
  <results_first_submitted_qc>September 23, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 19, 2020</results_first_posted>
  <last_update_submitted>September 23, 2020</last_update_submitted>
  <last_update_submitted_qc>September 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 2, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT03039699/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ergoferon</title>
          <description>Within the first 2 hours - 1 tablet every 30 minutes, followed by 3 more tablets at time intervals equally separated throughout the rest of the day; from day 2 to day 5 - 1 tablet 3 times daily.&#xD;
Ergoferon</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Within the first 2 hours - 1 tablet every 30 minutes, followed by 3 more tablets at time intervals equally separated throughout the rest of the day; from day 2 to day 5 - 1 tablet 3 times daily.&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="127"/>
                <participants group_id="P2" count="132"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="105"/>
                <participants group_id="P2" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Incorrect inclusion</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of data to assess study endpoint</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Bacterial infection</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ergoferon</title>
          <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>1 tablet 3 times a day&#xD;
Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="127"/>
            <count group_id="B2" value="132"/>
            <count group_id="B3" value="259"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="132"/>
                    <count group_id="B3" value="259"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="127"/>
                    <measurement group_id="B2" value="132"/>
                    <measurement group_id="B3" value="259"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="132"/>
                    <count group_id="B3" value="259"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.3" spread="1.5"/>
                    <measurement group_id="B2" value="2.3" spread="1.4"/>
                    <measurement group_id="B3" value="2.3" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="132"/>
                    <count group_id="B3" value="259"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="113"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Uzbekistan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="132"/>
                    <count group_id="B3" value="259"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Russia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="127"/>
                    <count group_id="B2" value="132"/>
                    <count group_id="B3" value="259"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Average Diarrhea Duration.</title>
        <description>Diarrhea duration is considered as the time between receiving the first dose of investigational medicine /placebo and the normal consistency of stool pattern (to the previous stool consistency before diarrhea), i.e.&#xD;
time to the first loose stool which is followed by two normal consistency stools over 24 h (infants may have three episodes of loose stool over a 24-hour period), or&#xD;
time to ≤3 episodes of stool occurring over 24 h, at least 2 of which are normal consistency stools, or&#xD;
time to the absence of stools for ≥12 h which is not followed by new episodes of diarrhea (total stool frequency over 24 h - less than 3 times).</description>
        <time_frame>On days 1-10 of observation period.</time_frame>
        <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Average Diarrhea Duration.</title>
          <description>Diarrhea duration is considered as the time between receiving the first dose of investigational medicine /placebo and the normal consistency of stool pattern (to the previous stool consistency before diarrhea), i.e.&#xD;
time to the first loose stool which is followed by two normal consistency stools over 24 h (infants may have three episodes of loose stool over a 24-hour period), or&#xD;
time to ≤3 episodes of stool occurring over 24 h, at least 2 of which are normal consistency stools, or&#xD;
time to the absence of stools for ≥12 h which is not followed by new episodes of diarrhea (total stool frequency over 24 h - less than 3 times).</description>
          <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.4" lower_limit="37.9" upper_limit="49"/>
                    <measurement group_id="O2" value="54.7" lower_limit="49" upper_limit="60.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.004</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Without Diarrhea.</title>
        <description>Based on medical records.</description>
        <time_frame>48, 72 and 96 hours of the treatment.</time_frame>
        <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Without Diarrhea.</title>
          <description>Based on medical records.</description>
          <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>48 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62"/>
                    <measurement group_id="O2" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86"/>
                    <measurement group_id="O2" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98"/>
                    <measurement group_id="O2" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>48 hours timepoint comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0675</p_value>
            <p_value_desc>p-value adjusted for multiple comparisons using Holm method</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>72 hours timepoint comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0675</p_value>
            <p_value_desc>p-value adjusted for multiple comparisons using Holm method</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>96 hours timepoint comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5569</p_value>
            <p_value_desc>p-value adjusted for multiple comparisons using Holm method</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Recovery.</title>
        <description>Based on medical records. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).</description>
        <time_frame>48, 72 and 96 hours of the treatment.</time_frame>
        <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Recovery.</title>
          <description>Based on medical records. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).</description>
          <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>48 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88"/>
                    <measurement group_id="O2" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>48 hours timepoint comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0696</p_value>
            <p_value_desc>p-value adjusted for multiple comparisons using Holm method</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>72 hours timepoint comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0696</p_value>
            <p_value_desc>p-value adjusted for multiple comparisons using Holm method</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>96 hours timepoint comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1998</p_value>
            <p_value_desc>p-value adjusted for multiple comparisons using Holm method</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Illness Duration.</title>
        <description>From the enrollment to the recovery. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).</description>
        <time_frame>On days 1-10 of observation period.</time_frame>
        <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Average Illness Duration.</title>
          <description>From the enrollment to the recovery. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).</description>
          <population>2 patients in Ergoferon group and 2 patients in Placebo group had no primary outcome data</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.8" lower_limit="35.3" upper_limit="46.3"/>
                    <measurement group_id="O2" value="53.0" lower_limit="47.2" upper_limit="58.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0039</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Clinical Dehydration Scale Score.</title>
        <description>Based on medical records. Clinical Dehydration Scale score is more or equal 1. Note: minimum values - 0 points, maximum values - 8 points. Interpretation: 0 points - no dehydration, from 1 to 4 points - light dehydration, 5-8 points - average/severe dehydration.</description>
        <time_frame>24, 48, and 72 hours of the treatment.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Total Clinical Dehydration Scale Score.</title>
          <description>Based on medical records. Clinical Dehydration Scale score is more or equal 1. Note: minimum values - 0 points, maximum values - 8 points. Interpretation: 0 points - no dehydration, from 1 to 4 points - light dehydration, 5-8 points - average/severe dehydration.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="105"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="1.3" upper_limit="1.8"/>
                    <measurement group_id="O2" value="1.5" lower_limit="1.2" upper_limit="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" lower_limit="0.2" upper_limit="0.5"/>
                    <measurement group_id="O2" value="0.3" lower_limit="0.1" upper_limit="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" lower_limit="0" upper_limit="0.2"/>
                    <measurement group_id="O2" value="0.1" lower_limit="0" upper_limit="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.89</p_value>
            <p_value_desc>The p-value associated with &quot;treatment*visit&quot; interaction of total CDS score from 24 hours to 48 and 72 hours of treatment between Ergoferon and Placebo treatment groups. Model includes treatment, visit and treatment*visit interaction.</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Vomiting Duration (if Any).</title>
        <description>Based on medical records.</description>
        <time_frame>On days 1-10 of observation period.</time_frame>
        <population>Vomiting occured in 64.8% patients of Ergoferon group and 71.1% patients of placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Average Vomiting Duration (if Any).</title>
          <description>Based on medical records.</description>
          <population>Vomiting occured in 64.8% patients of Ergoferon group and 71.1% patients of placebo group.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.6" lower_limit="35.1" upper_limit="54.1"/>
                    <measurement group_id="O2" value="57.9" lower_limit="48.4" upper_limit="67.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0044</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Negative PCR Tests.</title>
        <description>Based on medical records.</description>
        <time_frame>On days 3, 4, 6 and 10 of observation period.</time_frame>
        <population>PCR tests on days 4, 6 and 10 were run on less patients due to technical issues in laboratory</population>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Negative PCR Tests.</title>
          <description>Based on medical records.</description>
          <population>PCR tests on days 4, 6 and 10 were run on less patients due to technical issues in laboratory</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="81"/>
                <count group_id="O2" value="71"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="77"/>
                    <count group_id="O2" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="80"/>
                    <count group_id="O2" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="73"/>
                    <count group_id="O2" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Day 3 comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5488</p_value>
            <p_value_desc>nonadjusted p-value</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Day 4 comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8140</p_value>
            <p_value_desc>nonadjusted p-value</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Day 6 comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1248</p_value>
            <p_value_desc>nonadjusted p-value</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Day 10 comparison</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3889</p_value>
            <p_value_desc>nonadjusted p-value</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Worsening of Illness and/or Hospital-acquired Infection.</title>
        <description>Based on medical records. Worsening of illness: an increase in dehydration scores and worsening of non-specific symptoms, as evidenced by a decline in general appearance, increasing fatigue and drowsiness, refusal to eat and drink, severe tachycardia/bradycardia, unstable hemodynamics, tachypnea, hypo- or hyperventilation, circulation disorders, peripheral cyanosis, sunken eyes, severe dryness of skin and mucous/tongue, poor tissue turgor, absent tears, persistent vomiting, anuria/acute kidney injury, seizure/convulsions, and meningismus. Hospital-acquired infection: a viral or bacterial infection (intestinal, respiratory or urinary tract infection, etc.) occurring after at least 48 h of hospital stay and confirmed by laboratory tests.</description>
        <time_frame>On days 1-10 of observation period.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ergoferon</title>
            <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 tablet 3 times a day&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Worsening of Illness and/or Hospital-acquired Infection.</title>
          <description>Based on medical records. Worsening of illness: an increase in dehydration scores and worsening of non-specific symptoms, as evidenced by a decline in general appearance, increasing fatigue and drowsiness, refusal to eat and drink, severe tachycardia/bradycardia, unstable hemodynamics, tachypnea, hypo- or hyperventilation, circulation disorders, peripheral cyanosis, sunken eyes, severe dryness of skin and mucous/tongue, poor tissue turgor, absent tears, persistent vomiting, anuria/acute kidney injury, seizure/convulsions, and meningismus. Hospital-acquired infection: a viral or bacterial infection (intestinal, respiratory or urinary tract infection, etc.) occurring after at least 48 h of hospital stay and confirmed by laboratory tests.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="105"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3593</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse/Serious adverse events were collected for 10 days of the therapy and follow-up periods.</time_frame>
      <desc>Adverse/Serious adverse events were collected in patients of the Safety population (n=259).</desc>
      <group_list>
        <group group_id="E1">
          <title>Ergoferon</title>
          <description>1 tablet 3 times a day&#xD;
Ergoferon</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>1 tablet 3 times a day&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Purine metabolism disorder</sub_title>
                <description>Functional stomach upset. Disoder of purine metabolism (acetone vomiting).</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Increased levels of ALT</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Increased levels of AST</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Increase in the percentage of lymphocytes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <description>Decrease in the percentage of neutrophils</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hematochezia</sub_title>
                <description>The presence of blood in the stool.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Acute otitis media</sub_title>
                <description>Left-sided otitis media (acute, non-suppurative)</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Rotavirus infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Candida Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Positive test result for staphylococcus</sub_title>
                <description>Positive result of isolation and identification of staphylococcus. Discharge of staphylococcus from the nasopharynx.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Herpangina caused by Coxsackie virus</sub_title>
                <description>Vesicular pharyngitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocytes in urine</sub_title>
                <description>An increase in the number of leukocytes in the urine.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="132"/>
              </event>
              <event>
                <sub_title>Hyperphosphaturia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="132"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Mikhail Putilovskiy, MD, PhD, Clinical and Medical Department Director</name_or_title>
      <organization>Materia Medica Holding</organization>
      <phone>+74952761571 ext 302</phone>
      <email>PutilovskiyMA@materiamedica.ru</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03039699
org study id: MMH-ER-008
nct id: NCT03039699
lead sponsor: 
has dmc: No
The purpose of this study is to obtain additional data on efficacy and safety of Ergoferon in
      the treatment of viral intestinal infections in inpatient children.
Design: a multicenter, double-blind, placebo-controlled, randomized clinical trial in
      parallel groups.

      This study will enroll subjects of both sexes aged from 6 months to 6 years who are admitted
      to hospital within 48 h of the onset of acute intestinal infection (AII), presumably of viral
      aetiology. Patients to be enrolled in the screening will be children with typical viral
      gastroenteritis/enteritis symptoms. The key symptom is decreased in the consistency of stools
      (loose or liquid) and increased in the frequency of its evacuations (at list 3 time daily).
      Virus detection in stool samples will be performed by polymerase chain reaction (PCR).

      After the parent/adopter signs a parents/adopters information sheet (Informed Consent form)
      for the child's participation in the clinical trial, the recording of medical history data, a
      medical examination including the evaluation of symptoms on the Clinical Dehydration Scale
      (CDS) by pediatrician, and laboratory tests will be performed during Visit 1 (Day 1). If
      inclusion criteria are met and non-inclusion criteria are absent (day 1), the patient will be
      included in the trial and randomized to administer either Ergoferon or Placebo.

      In addition to the standard/pathogenetic therapies, group 1 patients will take Ergoferon
      following a 5-day regimen, whereas group 2 patients will receive Placebo. The
      parents/adopters of the patient will be provided with a patient diary and instructed how to
      complete the diary.

      Before treatment stool specimens will be collected from the patients for detection and
      differentiation of Rotavirus A, Norovirus 2 genotype, Astrovirus, Adenovirus F, Shigella
      spp., enteroinvasive E.coli (EIEC), Salmonella spp., and thermophilic Campylobacter spp.
      using a PCR assay to diagnose the etiology of intestinal infection. In total, the patients
      will be monitored for 10 days (screening, randomization, treatment initiation - Day 1; the
      treatment on Days 1-5; observation in hospital - Day 6, and follow-up period - Day 7-10).
      During the treatment and inpatient observation periods (Days 1-6, Visits 1-6), the patients
      will be examined daily by a pediatrician, and the examination results, including the CDS
      scores, will be recorded in source documents. The patient's parent/adopter will complete the
      patient diary every day, recording the presence/absence of diarrhea signs, vomiting, and body
      temperature. The pediatrician will check them each time for the correctness of completion. On
      day 10 (after hospital discharge), Visit 7 will be done (as an in-person visit (a hospital or
      calling a doctor) or a distance, 'phone' visit) to interview the parents/adopters about the
      patient's health, presence of any complications, and use of medications (the pediatrician
      will use this information to complete a questionnaire). Collection of stool specimens and
      repeat PCR for Rotaviruses/Noroviruses/Astroviruses/Adenoviruses, Shigella spp., EIEC,
      Salmonella spp., and Campylobacter spp. will be performed on Days 3, 4, and 6 of inpatient
      observation and after discharge from the hospital (Day 10); collection of blood and urine
      specimens for safety tests will be carried out at baseline and before hospital discharge (day
      6). The recording of the intake of study therapies and of concomitant medications as well as
      the assessment of compliance with and safety of the study therapies will be performed on Days
      2-6 and 10.

      Patients who recovered while in hospital and are discharged from the unit earlier than at 5
      days will undergo the procedures of Visit 6, including the collection of biological specimens
      for PCR (efficacy evaluation) and biochemistry, blood test and urinalysis (safety
      assessment). The parents/adopters will be given the blister pack with the remaining study
      drug so that the patient can continue the treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Average Diarrhea Duration.
time frame: On days 1-10 of observation period.
description: Diarrhea duration is considered as the time between receiving the first dose of investigational medicine /placebo and the normal consistency of stool pattern (to the previous stool consistency before diarrhea), i.e.
time to the first loose stool which is followed by two normal consistency stools over 24 h (infants may have three episodes of loose stool over a 24-hour period), or
time to ≤3 episodes of stool occurring over 24 h, at least 2 of which are normal consistency stools, or
time to the absence of stools for ≥12 h which is not followed by new episodes of diarrhea (total stool frequency over 24 h - less than 3 times).
measure: Percentage of Patients Without Diarrhea.
time frame: 48, 72 and 96 hours of the treatment.
description: Based on medical records.
measure: Percentage of Patients With Recovery.
time frame: 48, 72 and 96 hours of the treatment.
description: Based on medical records. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).
measure: Average Illness Duration.
time frame: On days 1-10 of observation period.
description: From the enrollment to the recovery. Recovery criteria: absence of diarrhea, vomiting, symptoms of dehydration, and increased body temperature (based on daily examinations by pediatrician).
measure: Total Clinical Dehydration Scale Score.
time frame: 24, 48, and 72 hours of the treatment.
description: Based on medical records. Clinical Dehydration Scale score is more or equal 1. Note: minimum values - 0 points, maximum values - 8 points. Interpretation: 0 points - no dehydration, from 1 to 4 points - light dehydration, 5-8 points - average/severe dehydration.
measure: Average Vomiting Duration (if Any).
time frame: On days 1-10 of observation period.
description: Based on medical records.
measure: Percentage of Patients With Negative PCR Tests.
time frame: On days 3, 4, 6 and 10 of observation period.
description: Based on medical records.
measure: Percentage of Patients With Worsening of Illness and/or Hospital-acquired Infection.
time frame: On days 1-10 of observation period.
description: Based on medical records. Worsening of illness: an increase in dehydration scores and worsening of non-specific symptoms, as evidenced by a decline in general appearance, increasing fatigue and drowsiness, refusal to eat and drink, severe tachycardia/bradycardia, unstable hemodynamics, tachypnea, hypo- or hyperventilation, circulation disorders, peripheral cyanosis, sunken eyes, severe dryness of skin and mucous/tongue, poor tissue turgor, absent tears, persistent vomiting, anuria/acute kidney injury, seizure/convulsions, and meningismus. Hospital-acquired infection: a viral or bacterial infection (intestinal, respiratory or urinary tract infection, etc.) occurring after at least 48 h of hospital stay and confirmed by laboratory tests.
arm group label: Ergoferon
arm group type: Experimental
description: Tablet for oral use. Dose per administration - 1 tablet per intake (outside a meal/feeding). Within the first 2 hours - 1 tablet every 30 minutes, followed by 3 more tablets at time intervals equally separated throughout the rest of the day; from day 2 to day 5 - 1 tablet 3 times daily.
arm group label: Placebo
arm group type: Placebo Comparator
description: Tablet for oral use. Dose per administration - 1 tablet per intake (outside a meal/feeding). Within the first 2 hours - 1 tablet every 30 minutes, followed by 3 more tablets at time intervals equally separated throughout the rest of the day; from day 2 to day 5 - 1 tablet 3 times daily.
intervention type: Drug
intervention name: Ergoferon
arm group label: Ergoferon
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Months
maximum age: 6 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
country: Uzbekistan
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 