<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/NCT04400110</url>
  </required_header>
  <id_info>
    <org_study_id>RC 10/18</org_study_id>
    <nct_id>NCT04400110</nct_id>
  </id_info>
  <brief_title>Short Therapy for Febrile UTI in Childhood</brief_title>
  <official_title>Shortened Antibiotic Therapy for Febrile Urinary Tract Infection (UTI) in Childhood: a Multicenter Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Burlo Garofolo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS Burlo Garofolo</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Febrile urinary tract infections (UTIs) are common in children, but there is no consensus&#xD;
      concerning the duration of the antibiotic treatment. Current recommendations include the use&#xD;
      of an oral antibiotic, chosen between amoxicillin and clavulanic acid or a third-generation&#xD;
      cephalosporin (ceftibuten), for a minimum of seven to a maximum of 14 days. In an antibiotic&#xD;
      overuse-sparing model, proper evaluation of a shorter therapy in the treatment of febrile UTI&#xD;
      in childhood is lacking.&#xD;
&#xD;
      The objective of this randomized controlled trial is to assess the non inferiority of a five&#xD;
      days oral course of amoxicillin and clavulanic acid vs the standard 10-day regimen in the&#xD;
      treatment of febrile UTIs in children.&#xD;
&#xD;
      The trial results might provide evidence of the non-inferiority of a short duration of the&#xD;
      antibiotic course for the treatment of febrile UTI in childhood, contributing to a reduction&#xD;
      in the over-use of antibiotics and consequently limiting the emergence of antibiotic&#xD;
      resistance.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 8, 2020</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of infection recurrence</measure>
    <time_frame>within 30 days after the end of the intervention</time_frame>
    <description>Infection recurrence rate is defined as the reappearance of signs and symptoms of febrile UTI by the first day after the end of antibiotic therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of complete resolution of signs and symptoms</measure>
    <time_frame>within 30 days after the end of the intervention</time_frame>
    <description>The complete resolution of the signs and symptoms (clinical assessment and urinalysis) related to the infection evaluated at the end of the treatment, without the need for additional or alternative antibiotic therapy (short term clinical efficacy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of antibiotic-resistant or of opportunistic strains in relapses</measure>
    <time_frame>within 30 days after the end of the intervention</time_frame>
    <description>Antibiotic resistance is defined as the presence of positive urinalysis and positive urine culture for a single type of bacterium resistant to amoxicillin and clavulanic acid, after treatment in case of relapse. The bacterial growth will be considered significant if &gt;105 colony-forming unit/ml (CFU/ml) (&gt;104 CFU/ml for urine samples collected by bladder catheterization). Urine cultures containing more than one bacterial species will be considered contaminated.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">154</enrollment>
  <condition>Urinary Tract Infections</condition>
  <arm_group>
    <arm_group_label>Short treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 5 consecutive days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard treatment group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 10 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amoxicillin and Clavulanic Acid in Oral Dose Form</intervention_name>
    <description>50 mg/kg three times daily administered orally</description>
    <arm_group_label>Short treatment group</arm_group_label>
    <arm_group_label>Standard treatment group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age from 3 months to 5 years;&#xD;
&#xD;
          2. Clinical diagnosis of febrile UTI, defined by fever ≥38°C and positive result of&#xD;
             urinalysis (nitrite and/or leukocyte esterase positivity) in two consecutive urine&#xD;
             samples collected by bladder catheterization or clean catch (19). The diagnosis of UTI&#xD;
             will be then confirmed by positive urine culture for a single type of bacterium with a&#xD;
             charge&gt; 105 CFU /ml as per the Recommendations of the Italian Society of Pediatric&#xD;
             Nephrology (SINePe) (19).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. &quot;Complicated&quot; febrile UTI (septic appearance, repeated vomiting impeding oral&#xD;
             administration of the antibiotic, severe-moderate dehydration with the need for&#xD;
             intravenous antibiotic therapy)&#xD;
&#xD;
          2. Presence of an inserted urinary catheter&#xD;
&#xD;
          3. Immunodeficiency&#xD;
&#xD;
          4. Hypersensitivity to the active substance or other beta-lactam antibiotics&#xD;
&#xD;
          5. Any antibiotic treatment received in the previous 15 days.&#xD;
&#xD;
          6. Presence of another poorly controlled chronic medical condition (diabetes,&#xD;
             inflammatory bowel disease, etc.)&#xD;
&#xD;
          7. Presence of neurological bladder&#xD;
&#xD;
          8. Presence of phenylketonuria or glucose-galactose malabsorption&#xD;
&#xD;
          9. Intestinal malabsorption&#xD;
&#xD;
         10. Poor compliance&#xD;
&#xD;
         11. History of jaundice or liver failure positive&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Egidio Barbi, MD Prof</last_name>
    <role>Study Chair</role>
    <affiliation>Institute for maternal and child health Burlo Garofolo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marco Pennesi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute for maternal and child health Burlo Garofolo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Policlinico S.Orsola-Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>Emilia Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Maria delle Croci Hospital</name>
      <address>
        <city>Ravenna</city>
        <state>Emilia Romagna</state>
        <zip>48121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Polo</name>
      <address>
        <city>Monfalcone</city>
        <state>Friuli Venezia Giulia</state>
        <zip>34074</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pediatric Department, Santa Maria degli Angeli Hospital</name>
      <address>
        <city>Pordenone</city>
        <state>Friuli Venezia Giulia</state>
        <zip>33170</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute for Maternal and Child Health IRCCS Burlo Garofolo</name>
      <address>
        <city>Trieste</city>
        <state>Friuli Venezia Giulia</state>
        <zip>34137</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASUIUD Azienda sanitaria universitaria integrata di Udine</name>
      <address>
        <city>Udine</city>
        <state>Friuli Venezia Giulia</state>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Agostino Gemelli - IRCCS City Rome</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCSS Ca Granda, Policlinico di Milano</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedali Riuniti di Ancona - Ospedale Salesi</name>
      <address>
        <city>Ancona</city>
        <state>Marche</state>
        <zip>60123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U.G. Martino</name>
      <address>
        <city>Messina</city>
        <state>Sicilia</state>
        <zip>98124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Martino Hospital</name>
      <address>
        <city>Belluno</city>
        <state>Veneto</state>
        <zip>32100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Woman and Child Health, University of Padua City</name>
      <address>
        <city>Padua</city>
        <state>Veneto</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOC Pediatria Ospedale Ca' Foncello</name>
      <address>
        <city>Treviso</city>
        <state>Veneto</state>
        <zip>31100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>short antibiotic therapy</keyword>
  <keyword>urinary tract infection</keyword>
  <keyword>children</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Urinary Tract Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Clavulanic Acids</mesh_term>
    <mesh_term>Clavulanic Acid</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/NCT04400110
org study id: RC 10/18
nct id: NCT04400110
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Febrile urinary tract infections (UTIs) are common in children, but there is no consensus
      concerning the duration of the antibiotic treatment. Current recommendations include the use
      of an oral antibiotic, chosen between amoxicillin and clavulanic acid or a third-generation
      cephalosporin (ceftibuten), for a minimum of seven to a maximum of 14 days. In an antibiotic
      overuse-sparing model, proper evaluation of a shorter therapy in the treatment of febrile UTI
      in childhood is lacking.

      The objective of this randomized controlled trial is to assess the non inferiority of a five
      days oral course of amoxicillin and clavulanic acid vs the standard 10-day regimen in the
      treatment of febrile UTIs in children.

      The trial results might provide evidence of the non-inferiority of a short duration of the
      antibiotic course for the treatment of febrile UTI in childhood, contributing to a reduction
      in the over-use of antibiotics and consequently limiting the emergence of antibiotic
      resistance.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of infection recurrence
time frame: within 30 days after the end of the intervention
description: Infection recurrence rate is defined as the reappearance of signs and symptoms of febrile UTI by the first day after the end of antibiotic therapy
measure: Rate of complete resolution of signs and symptoms
time frame: within 30 days after the end of the intervention
description: The complete resolution of the signs and symptoms (clinical assessment and urinalysis) related to the infection evaluated at the end of the treatment, without the need for additional or alternative antibiotic therapy (short term clinical efficacy)
measure: Rate of antibiotic-resistant or of opportunistic strains in relapses
time frame: within 30 days after the end of the intervention
description: Antibiotic resistance is defined as the presence of positive urinalysis and positive urine culture for a single type of bacterium resistant to amoxicillin and clavulanic acid, after treatment in case of relapse. The bacterial growth will be considered significant if >105 colony-forming unit/ml (CFU/ml) (>104 CFU/ml for urine samples collected by bladder catheterization). Urine cultures containing more than one bacterial species will be considered contaminated.
arm group label: Short treatment group
arm group type: Experimental
description: Amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 5 consecutive days
arm group label: Standard treatment group
arm group type: Active Comparator
description: amoxicillin and clavulanic acid 50 mg/kg three times daily administered orally for 10 consecutive days
intervention type: Drug
intervention name: Amoxicillin and Clavulanic Acid in Oral Dose Form
description: 50 mg/kg three times daily administered orally
arm group label: Short treatment group
arm group label: Standard treatment group
criteria: 
gender: All
minimum age: 3 Months
maximum age: 5 Years
healthy volunteers: No
last name: Egidio Barbi, MD Prof
role: Study Chair
affiliation: Institute for maternal and child health Burlo Garofolo
last name: Marco Pennesi, MD
role: Principal Investigator
affiliation: Institute for maternal and child health Burlo Garofolo
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Infections
mesh term: Urinary Tract Infections
mesh term: Amoxicillin
mesh term: Clavulanic Acids
mesh term: Clavulanic Acid
sharing ipd: No