<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/NCT03031210</url>
  </required_header>
  <id_info>
    <org_study_id>BID pneumonia</org_study_id>
    <nct_id>NCT03031210</nct_id>
  </id_info>
  <brief_title>Twice Daily Treatment With Amoxicillin for Non-severe Community Acquired Pneumonia.</brief_title>
  <official_title>Treatment of Non-severe Community Acquired Pneumonia With Twice Daily Compared to Thrice Daily Regimen- A Non-inferiority Pragmatic Randomized-controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Justine's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Justine's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study will be to evaluate whether a twice-daily antibiotic regimen is&#xD;
      non-inferior to a thrice-daily regimen for the treatment of non-severe community acquired&#xD;
      pneumonia in children presenting at a paediatric Emergency Department (ED).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A single-center, non-blinded, pragmatic, randomized-controlled, non-inferiority clinical&#xD;
      trial will be conducted in an urban, university-affiliated, tertiary care pediatric hospital&#xD;
      ED. All patients three months old to 18 years of age who had symptoms and signs suggestive of&#xD;
      non-severe community acquired pneumonia based on respiratory complaints and a pulmonary&#xD;
      infiltrate identified by trained paediatricians or emergency physicians will be eligible to&#xD;
      the present study. Study participants will be randomly allocated to receive either&#xD;
      amoxicillin (90mg/kg per day) in twice or thrice daily regimen. Primary outcome will be&#xD;
      treatment failure within 10 days of enrolment as defined by hospitalisation, need for a&#xD;
      change in antibiotic (persistence of fever at 72 hours, clinical deterioration, comorbid&#xD;
      condition or development of serious adverse reactions) and death. ED revisits within 72&#xD;
      hours, second course of antibiotic and clinical recurrence rates will be evaluated in the&#xD;
      follow-up assessments as well as percent of adverse events encountered, number of days missed&#xD;
      (work, school or daycare), coverage vaccination rate, protocol adherence and patient and&#xD;
      parental satisfaction. The primary analysis will use an intention-to-treat approach.&#xD;
      Per-protocol analysis will also be carried to compare the failure rate. Accounting to a&#xD;
      maximal 10% drop-off rate, a sample size of 685 participants per arm was calculated to have a&#xD;
      power of 90% to identify a difference of ≤ 5% with an alpha value of 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 11, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical failure within 10 days of enrolment</measure>
    <time_frame>Day 10 (after enrolment)</time_frame>
    <description>As a primary outcome, clinical failure will be defined by any of the following occurring within 10 days of enrolment:&#xD;
Death or hospitalisation&#xD;
A need for a change in antibiotic according to the treating physician. In our settings, common reasons to change antibiotic are:&#xD;
Persistence of fever at 72h&#xD;
Clinical deterioration:&#xD;
• Clinical deterioration will include the development of lower chest-wall indrawing, central cyanosis, stridor while calm, or danger signs as defined by: inability to drink or breastfeed, convulsions, persistent vomiting, lethargy, or unconsciousness at any time during a child's treatment.&#xD;
Development of a comorbid condition such as a meningitis, bacteriemia, osteomyelitis or septic arthritis&#xD;
Allergic reaction</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Emergency department revisit within 72 hours</measure>
    <time_frame>72 hours</time_frame>
    <description>Return to the emergency department in the following 72 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Second course of antibiotic</measure>
    <time_frame>1 month</time_frame>
    <description>Necessity of second course of antibiotics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical recurrence</measure>
    <time_frame>1 month</time_frame>
    <description>Another diagnosis of pneumonia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>10 days</time_frame>
    <description>Any adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of working days missed by caregivers or school/daycare days missed by patients</measure>
    <time_frame>1 month</time_frame>
    <description>Total number of days missed by caregivers or school/daycare days missed by the parents</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's and parents satisfaction with the discharge instructions' provided and the ease of administration</measure>
    <time_frame>10 days</time_frame>
    <description>Measured on a likert scale through a telephone survey</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1370</enrollment>
  <condition>Community-acquired Pneumonia</condition>
  <arm_group>
    <arm_group_label>Twice a day regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will received a prescription of amoxicillin (90mg/kg/day) divided in two doses daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Thrice a day regimen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will received a prescription of amoxicillin (90mg/kg/day) divided in three doses daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin</intervention_name>
    <description>(90 mg/kg/day) twice daily</description>
    <arm_group_label>Thrice a day regimen</arm_group_label>
    <arm_group_label>Twice a day regimen</arm_group_label>
    <other_name>Amoxil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients 3 months to 18 years of age attending the pediatric ED and diagnosed with&#xD;
             a non-severe pneumonia, will be considered for enrolment. More precisely, the&#xD;
             following inclusion criteria will be required:&#xD;
&#xD;
               1. Presence of respiratory symptoms (cough and/or dyspnea)&#xD;
&#xD;
               2. Presence of signs of pneumonia (tachypnea, abnormal breath sounds, crackles)&#xD;
&#xD;
               3. Presence of fever&#xD;
&#xD;
               4. Positive chest radiography as interpreted by the treating physician&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any danger signs associated with pneumonia (severe indrawing, shock or severe&#xD;
             dehydration, empyema, important pleural effusion, pulmonary abcess or pneumatocoele)&#xD;
&#xD;
          -  History of anaphylactic or allergic reaction to penicillin or amoxicillin according to&#xD;
             the treating physician.&#xD;
&#xD;
          -  History of a serious nonimmunoglobulin E-mediated reactions (eg, Stevens-Johnson&#xD;
             syndrome or toxic epidermal necrolysis) attributed to amoxicilin.&#xD;
&#xD;
          -  Caregiver unable to provide consent (language barrier or lack of caregiver presence)&#xD;
&#xD;
          -  Underlying unstable chronic illness (ie. cystic fibrosis, immune suppression, active&#xD;
             tuberculosis, bronchiectasis or active pulmonary malignancies)&#xD;
&#xD;
          -  Persistent/chronic pneumonia syndromes (with symptoms for &gt;2 weeks), suspected by the&#xD;
             physician to be caused by atypical pathogens, hospital- acquired pneumonia (been&#xD;
             hospitalized within 2 weeks prior to enrolment), aspiration pneumonia or recurrent&#xD;
             pneumonias.&#xD;
&#xD;
          -  Any history of receiving amoxicillin within the past month&#xD;
&#xD;
          -  Need hospitalisation for any other reasons (ie. persistent vomiting, severe&#xD;
             life-threatening infection such as septicaemia or meningitis requiring intravenous&#xD;
             antimicrobial agents)&#xD;
&#xD;
          -  Previous participation in study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jocelyn Gravel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sainte-Justine Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jocelyn Gravel, MD</last_name>
    <phone>514-345-4931</phone>
    <phone_ext>2559</phone_ext>
    <email>graveljocelyn@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ariane Boutin, MD</last_name>
    <phone>514-345-4931</phone>
    <email>arianeboutin@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU Sainte-Justine</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jocelyn Gravel, MD</last_name>
      <phone>514-345-4931</phone>
      <phone_ext>2559</phone_ext>
      <email>graveljocelyn@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Ariane Boutin, MD</last_name>
      <phone>514-345-4931</phone>
      <email>arianeboutin@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Jocelyn Gravel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Boutin Ariane, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Benoit Carriere, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marc Lebel, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michel Roy, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Justine's Hospital</investigator_affiliation>
    <investigator_full_name>Jocelyn Gravel</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Non-severe community-acquired pneumonia</keyword>
  <keyword>Amoxicillin treatment</keyword>
  <keyword>Twice daily antibiotic regimen</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03031210
org study id: BID pneumonia
nct id: NCT03031210
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim of this study will be to evaluate whether a twice-daily antibiotic regimen is
      non-inferior to a thrice-daily regimen for the treatment of non-severe community acquired
      pneumonia in children presenting at a paediatric Emergency Department (ED).
A single-center, non-blinded, pragmatic, randomized-controlled, non-inferiority clinical
      trial will be conducted in an urban, university-affiliated, tertiary care pediatric hospital
      ED. All patients three months old to 18 years of age who had symptoms and signs suggestive of
      non-severe community acquired pneumonia based on respiratory complaints and a pulmonary
      infiltrate identified by trained paediatricians or emergency physicians will be eligible to
      the present study. Study participants will be randomly allocated to receive either
      amoxicillin (90mg/kg per day) in twice or thrice daily regimen. Primary outcome will be
      treatment failure within 10 days of enrolment as defined by hospitalisation, need for a
      change in antibiotic (persistence of fever at 72 hours, clinical deterioration, comorbid
      condition or development of serious adverse reactions) and death. ED revisits within 72
      hours, second course of antibiotic and clinical recurrence rates will be evaluated in the
      follow-up assessments as well as percent of adverse events encountered, number of days missed
      (work, school or daycare), coverage vaccination rate, protocol adherence and patient and
      parental satisfaction. The primary analysis will use an intention-to-treat approach.
      Per-protocol analysis will also be carried to compare the failure rate. Accounting to a
      maximal 10% drop-off rate, a sample size of 685 participants per arm was calculated to have a
      power of 90% to identify a difference of ≤ 5% with an alpha value of 0.05.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Clinical failure within 10 days of enrolment
time frame: Day 10 (after enrolment)
description: As a primary outcome, clinical failure will be defined by any of the following occurring within 10 days of enrolment:
Death or hospitalisation
A need for a change in antibiotic according to the treating physician. In our settings, common reasons to change antibiotic are:
Persistence of fever at 72h
Clinical deterioration:
• Clinical deterioration will include the development of lower chest-wall indrawing, central cyanosis, stridor while calm, or danger signs as defined by: inability to drink or breastfeed, convulsions, persistent vomiting, lethargy, or unconsciousness at any time during a child's treatment.
Development of a comorbid condition such as a meningitis, bacteriemia, osteomyelitis or septic arthritis
Allergic reaction
measure: Emergency department revisit within 72 hours
time frame: 72 hours
description: Return to the emergency department in the following 72 hours
measure: Second course of antibiotic
time frame: 1 month
description: Necessity of second course of antibiotics
measure: Clinical recurrence
time frame: 1 month
description: Another diagnosis of pneumonia
measure: Adverse events
time frame: 10 days
description: Any adverse event
measure: Number of working days missed by caregivers or school/daycare days missed by patients
time frame: 1 month
description: Total number of days missed by caregivers or school/daycare days missed by the parents
measure: Patient's and parents satisfaction with the discharge instructions' provided and the ease of administration
time frame: 10 days
description: Measured on a likert scale through a telephone survey
arm group label: Twice a day regimen
arm group type: Experimental
description: Patients will received a prescription of amoxicillin (90mg/kg/day) divided in two doses daily.
arm group label: Thrice a day regimen
arm group type: Active Comparator
description: Patients will received a prescription of amoxicillin (90mg/kg/day) divided in three doses daily.
intervention type: Drug
intervention name: Amoxicillin
description: (90 mg/kg/day) twice daily
arm group label: Thrice a day regimen
arm group label: Twice a day regimen
other name: Amoxil
criteria: 
gender: All
minimum age: 3 Months
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jocelyn Gravel, MD
role: Principal Investigator
affiliation: Sainte-Justine Hospital
last name: Jocelyn Gravel, MD
phone: 514-345-4931
phone ext: 2559
email: graveljocelyn@hotmail.com
last name: Ariane Boutin, MD
phone: 514-345-4931
email: arianeboutin@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: St. Justine's Hospital
investigator full name: Jocelyn Gravel
investigator title: Principal investigator
mesh term: Pneumonia
mesh term: Amoxicillin
sharing ipd: No