<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/NCT01690637</url>
  </required_header>
  <id_info>
    <org_study_id>CDC-NCIRD-6330</org_study_id>
    <nct_id>NCT01690637</nct_id>
  </id_info>
  <brief_title>Panama and El Salvador Children's Oseltamivir Study</brief_title>
  <acronym>PECOS</acronym>
  <official_title>Efficacy of Early Oseltamivir Phosphate Treatment at Hospital Admission to Reduce Severity of Illness Among Children Aged Less Than 10 Years Hospitalized With Influenza in El Salvador and Panama</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universidad del Valle, Guatemala</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Nacional San Juan de Dios de Santa Ana, El Salvador</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Nacional San Juan de Dios de San Miguel, El Salvador</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Del Nino, Panama</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital de Especialidades Pediátricas Omar Torrijos Herrera, Panama</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Jose Domingo de Obaldia, Panama</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centers for Disease Control and Prevention</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, randomized, double-blind, placebo-controlled trial that will be&#xD;
      conducted in tertiary care pediatric hospitals in El Salvador and Panama. The primary purpose&#xD;
      of this study is to determine whether empiric oseltamivir phosphate treatment given at the&#xD;
      time of hospital admission to children less than 10 years of age hospitalized with influenza&#xD;
      can effectively reduce their illness severity. Additional objectives are to: 1) evaluate the&#xD;
      tolerability of oseltamivir phosphate treatment, 2) evaluate the effect of oseltamivir&#xD;
      treatment on viral clearance and development of oseltamivir-resistant influenza virus during&#xD;
      and after treatment in children hospitalized with influenza, 3) estimate the direct and&#xD;
      indirect costs of all-cause respiratory illness and influenza-associated respiratory illness&#xD;
      requiring hospitalization, and 4) evaluate the effect of empiric oseltamivir treatment during&#xD;
      the influenza season on these costs.&#xD;
&#xD;
      The primary study hypothesis is that children with laboratory-confirmed influenza receiving&#xD;
      empiric oseltamivir phosphate treatment initiated at the time of hospital admission will have&#xD;
      a shorter duration of hospitalization and a shorter time to resolution of signs of severe&#xD;
      respiratory illness compared to children receiving placebo. The secondary study hypotheses&#xD;
      are that children with laboratory-confirmed influenza receiving oseltamivir phosphate&#xD;
      treatment will have a reduction in the time to non-detectable influenza virus and influenza&#xD;
      viral RNA and children with all-cause respiratory illness receiving oseltamivir phosphate&#xD;
      will not be more likely to experience severe adverse events than children receiving placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slower than anticipated participant accrual&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</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>Length of hospitalization</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected median of 7 days</time_frame>
    <description>Day 1 is defined as the day of arrival at the emergency department</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to resolution of increased work of breathing</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected median of 7 days</time_frame>
    <description>Increased work of breathing is defined as presence of 1 or more of the following: supraclavicular retractions, subcostal or intercostal retractions, nasal flaring, grunting, or need for noninvasive or invasive mechanical ventilation, and resolution is defined as 12 hours or more without increased work of breathing in a child with increased work of breathing at enrollment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to resolution of hypoxia</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected median of 7 days</time_frame>
    <description>Hypoxia is defined as O2 saturation less than 92% measured by pulse oximetry while breathing room air or need for noninvasive or invasive mechanical ventilation and resolution is defined as 12 hours or more without hypoxia in a child with hypoxia at enrollment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of new onset respiratory failure 24 hours or more after first dose of study medication</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected median of 7 days</time_frame>
    <description>Respiratory failure is defined by need for noninvasive or invasive mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of admission to intensive care unit 24 hours or more after first dose of study medication</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected median of 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of death 24 hours or more after first dose of study medication</measure>
    <time_frame>Participants will be followed up through 7 days after hospital discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to non-detectable influenza virus by viral culture and non-detectable influenza viral RNA by RT-PCR</measure>
    <time_frame>Participants will be followed for the duration of hospital stay (an expected median of 7 days) or up through 21 days of hospitalization, whichever is shorter</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children with oseltamivir resistant virus detected during or after oseltamivir phosphate treatment who had oseltamivir susceptible virus infection at enrollment</measure>
    <time_frame>Participants will be followed for the duration of hospital stay (an expected median of 7 days) or up through 21 days of hospitalization, whichever is shorter</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants experiencing adverse events (including severe and non-severe)</measure>
    <time_frame>Up through 7 days after hospital discharge</time_frame>
    <description>An adverse event is defined as any unfavorable or undesirable effect (sign, symptom, abnormality, or condition), regardless of causal relationship to study procedures or participation that occurs in participants while enrolled in this clinical trial. Any medical condition or sign/symptom that is present at the time the participant is screened is considered as baseline and not reported as an adverse event.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">721</enrollment>
  <condition>Influenza</condition>
  <condition>Human Influenza</condition>
  <arm_group>
    <arm_group_label>Oseltamivir phosphate suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants assigned to the oseltamivir phosphate treatment arm will receive the appropriate weight-based dose of oseltamivir phosphate every 12 hours for 10 doses. For children 0-11 months of age, oseltamivir phosphate will be dosed as 3mg/kg/dose every 12 hours. For children 12 months and older, oseltamivir phosphate will be dosed as follows: 30 mg every 12 hours for children up to 15kg, 45mg every 12 hours for children greater than 15kg up to 23 kg, 60mg every 12 hours for children greater than 23 up to 40kg, and 75mg every 12 hours for children greater than 40kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oseltamivir phosphate suspension</intervention_name>
    <arm_group_label>Oseltamivir phosphate suspension</arm_group_label>
    <other_name>Tamiflu</other_name>
  </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;
          -  Age &lt;10 years&#xD;
&#xD;
          -  Accompanied by a parent or guardian who has the capacity to grant and sign the written&#xD;
             informed consent and who has consented to enrollment&#xD;
&#xD;
          -  Has respiratory illness as defined by modified IMCI criteria for pneumonia:&#xD;
&#xD;
          -  Cough or sore throat AND Fast breathing, defined as respiratory rate 60 breaths per&#xD;
             minutes or greater for children 0 to &lt;2 months, OR respiratory rate 50 breaths per&#xD;
             minute or greater for children 2 to &lt;12 months, OR respiratory rate 40 breaths per&#xD;
             minute or greater for children 12 to &lt;60 months, OR respiratory rate 30 breaths per&#xD;
             minute or greater for children 5-9 years&#xD;
&#xD;
          -  Planned for hospital admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptom onset 7 days or more at the time of study screening where day 1 is the day of&#xD;
             symptom onset&#xD;
&#xD;
          -  Concomitant severe vomiting illness prior to enrollment that would preclude ability to&#xD;
             take medication orally defined as more than 3 vomiting episodes in the preceding 24&#xD;
             hours&#xD;
&#xD;
          -  Prematurity (birth at less than 37 weeks gestation) for children aged less than 3&#xD;
             months&#xD;
&#xD;
          -  Birth weight less than 2500 grams for children aged less than 3 months&#xD;
&#xD;
          -  Chronic supplemental oxygen requirement at home&#xD;
&#xD;
          -  Known history of renal dysfunction&#xD;
&#xD;
          -  History of gastrointestinal resection resulting in gastrointestinal abnormality that&#xD;
             might hinder absorption of oral medication (such as short-gut syndrome)&#xD;
&#xD;
          -  History of previous serious adverse reaction to oseltamivir phosphate&#xD;
&#xD;
          -  Receipt of oseltamivir phosphate during the 5 days prior to presentation at the&#xD;
             admitting hospital&#xD;
&#xD;
          -  Previous enrollment in this study during a hospitalization that ended less than 14&#xD;
             days prior to the current admission&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>9 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fatimah S Dawood, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centers for Disease Control and Prevention</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jorge Jara, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad del Valle, Guatemala</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Nacional San Juan de Dios de San Miguel</name>
      <address>
        <city>San Miguel</city>
        <country>El Salvador</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nacional San Juan de Dios de Santa Ana</name>
      <address>
        <city>Santa Ana</city>
        <country>El Salvador</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Jose Domingo de Obaldia</name>
      <address>
        <city>David</city>
        <country>Panama</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Especialidades Pediátricas Omar Torrijos Herrera</name>
      <address>
        <city>Panama City</city>
        <country>Panama</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Del Nino</name>
      <address>
        <city>Panama City</city>
        <country>Panama</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>El Salvador</country>
    <country>Panama</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <last_update_submitted>June 30, 2014</last_update_submitted>
  <last_update_submitted_qc>June 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centers for Disease Control and Prevention</investigator_affiliation>
    <investigator_full_name>Fatimah Dawood</investigator_full_name>
    <investigator_title>Medical Epidemiologist</investigator_title>
  </responsible_party>
  <keyword>Oseltamivir</keyword>
  <keyword>Tamiflu</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oseltamivir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01690637
org study id: CDC-NCIRD-6330
nct id: NCT01690637
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This is a prospective, randomized, double-blind, placebo-controlled trial that will be
      conducted in tertiary care pediatric hospitals in El Salvador and Panama. The primary purpose
      of this study is to determine whether empiric oseltamivir phosphate treatment given at the
      time of hospital admission to children less than 10 years of age hospitalized with influenza
      can effectively reduce their illness severity. Additional objectives are to: 1) evaluate the
      tolerability of oseltamivir phosphate treatment, 2) evaluate the effect of oseltamivir
      treatment on viral clearance and development of oseltamivir-resistant influenza virus during
      and after treatment in children hospitalized with influenza, 3) estimate the direct and
      indirect costs of all-cause respiratory illness and influenza-associated respiratory illness
      requiring hospitalization, and 4) evaluate the effect of empiric oseltamivir treatment during
      the influenza season on these costs.

      The primary study hypothesis is that children with laboratory-confirmed influenza receiving
      empiric oseltamivir phosphate treatment initiated at the time of hospital admission will have
      a shorter duration of hospitalization and a shorter time to resolution of signs of severe
      respiratory illness compared to children receiving placebo. The secondary study hypotheses
      are that children with laboratory-confirmed influenza receiving oseltamivir phosphate
      treatment will have a reduction in the time to non-detectable influenza virus and influenza
      viral RNA and children with all-cause respiratory illness receiving oseltamivir phosphate
      will not be more likely to experience severe adverse events than children receiving placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Length of hospitalization
time frame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
description: Day 1 is defined as the day of arrival at the emergency department
measure: Time to resolution of increased work of breathing
time frame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
description: Increased work of breathing is defined as presence of 1 or more of the following: supraclavicular retractions, subcostal or intercostal retractions, nasal flaring, grunting, or need for noninvasive or invasive mechanical ventilation, and resolution is defined as 12 hours or more without increased work of breathing in a child with increased work of breathing at enrollment
measure: Time to resolution of hypoxia
time frame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
description: Hypoxia is defined as O2 saturation less than 92% measured by pulse oximetry while breathing room air or need for noninvasive or invasive mechanical ventilation and resolution is defined as 12 hours or more without hypoxia in a child with hypoxia at enrollment
measure: Incidence of new onset respiratory failure 24 hours or more after first dose of study medication
time frame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
description: Respiratory failure is defined by need for noninvasive or invasive mechanical ventilation
measure: Incidence of admission to intensive care unit 24 hours or more after first dose of study medication
time frame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
measure: Incidence of death 24 hours or more after first dose of study medication
time frame: Participants will be followed up through 7 days after hospital discharge
measure: Time to non-detectable influenza virus by viral culture and non-detectable influenza viral RNA by RT-PCR
time frame: Participants will be followed for the duration of hospital stay (an expected median of 7 days) or up through 21 days of hospitalization, whichever is shorter
measure: Proportion of children with oseltamivir resistant virus detected during or after oseltamivir phosphate treatment who had oseltamivir susceptible virus infection at enrollment
time frame: Participants will be followed for the duration of hospital stay (an expected median of 7 days) or up through 21 days of hospitalization, whichever is shorter
measure: Proportion of participants experiencing adverse events (including severe and non-severe)
time frame: Up through 7 days after hospital discharge
description: An adverse event is defined as any unfavorable or undesirable effect (sign, symptom, abnormality, or condition), regardless of causal relationship to study procedures or participation that occurs in participants while enrolled in this clinical trial. Any medical condition or sign/symptom that is present at the time the participant is screened is considered as baseline and not reported as an adverse event.
arm group label: Oseltamivir phosphate suspension
arm group type: Active Comparator
description: Participants assigned to the oseltamivir phosphate treatment arm will receive the appropriate weight-based dose of oseltamivir phosphate every 12 hours for 10 doses. For children 0-11 months of age, oseltamivir phosphate will be dosed as 3mg/kg/dose every 12 hours. For children 12 months and older, oseltamivir phosphate will be dosed as follows: 30 mg every 12 hours for children up to 15kg, 45mg every 12 hours for children greater than 15kg up to 23 kg, 60mg every 12 hours for children greater than 23 up to 40kg, and 75mg every 12 hours for children greater than 40kg.
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Oseltamivir phosphate suspension
arm group label: Oseltamivir phosphate suspension
other name: Tamiflu
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: N/A
maximum age: 9 Years
healthy volunteers: No
last name: Fatimah S Dawood, MD
role: Principal Investigator
affiliation: Centers for Disease Control and Prevention
last name: Jorge Jara, MD
role: Principal Investigator
affiliation: Universidad del Valle, Guatemala
facility: 
facility: 
facility: 
facility: 
facility: 
country: El Salvador
country: Panama
responsible party type: Principal Investigator
investigator affiliation: Centers for Disease Control and Prevention
investigator full name: Fatimah Dawood
investigator title: Medical Epidemiologist
mesh term: Influenza, Human
mesh term: Oseltamivir