<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/NCT03801213</url>
  </required_header>
  <id_info>
    <org_study_id>18-HPNCL-03</org_study_id>
    <nct_id>NCT03801213</nct_id>
  </id_info>
  <brief_title>Evaluation of Urine Samples Obtained by Bladder Stimulation for the Diagnosis of Urinary Tract Infection in Infants</brief_title>
  <acronym>EEStiVeN</acronym>
  <official_title>Evaluation of the Bladder Stimulation, a Non-invasive Technique of Urine Collection, in Infant Less Than 6 Months to Diagnose Urinary Tract Infection: a Randomized Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondation Lenval</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondation Lenval</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Urinary tract infection (UTI) is the most common serious bacterial infection among infants.&#xD;
      Suprapubic aspiration and bladder catheterization are considered as the gold standard by the&#xD;
      American Academy of Pediatrics for the diagnosis, yet it is painful and invasive. In&#xD;
      contrast, the bladder stimulation technique has been shown to be a quick and non-invasive&#xD;
      approach to collect urine in young infants. Actually, the investigators don't have data on&#xD;
      bacterial contamination rates for clean-catch midstream urine collections using this&#xD;
      technique&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Urinary tract infection (UTI) is common in infants and needs to be diagnosed quickly. The&#xD;
      risk for urinary tract infection before the age of 2 years is about 1-4% in boys and 3-8% in&#xD;
      girls. A delay in diagnosis exposes to severe complications. In infants, the symptoms are not&#xD;
      specific. A good urinalysis quality is therefore necessary for the diagnosis of UTI.&#xD;
      Different techniques exist to collect urine samples in these children who do not control&#xD;
      their urination yet: supra pubic aspiration, catheterization, urine collection bag and clean&#xD;
      catch urine. The American Academy of Pediatrics (AAP) recommends supra pubic aspiration (1-9&#xD;
      % bacterial contamination) and urinary catheterization (8-14 % contamination) for collecting&#xD;
      urine but these techniques are invasive and painful. The sterile bag is a non-invasive method&#xD;
      of urine collection, with a high bacterial contamination rates (26-62%) leading to&#xD;
      unnecessary antibiotic treatment. Finally, clean catch urine is an accepted urine sample to&#xD;
      diagnose UTI according to the recommendations (13-27 % of bacterial contamination) but this&#xD;
      method is only possible for potty-trained children. Recent studies (Herreros et al, Altuntas&#xD;
      et al, Tran et al.) have shown that bladder stimulation, which consists of pubic tapping and&#xD;
      lumbar massage, would be a new, effective, non-invasive and safe method of collecting urine&#xD;
      in infants.&#xD;
&#xD;
      Bladder stimulation may be performed by a nurse or a physician. The steps of the bladder&#xD;
      stimulation technique are as follows: (a) cleaning the genital area with warm water and soap&#xD;
      b) bladder stimulation technique, requires the presence of 3 people: infants will be held&#xD;
      under their armpits by a parent over the bed, with legs dangling in males and hips flexed in&#xD;
      females. The nurse or technician will then alternate between bladder stimulation maneuvers:&#xD;
      gentle tapping in the suprapubic area at a frequency of 100 taps per minute for 30 seconds&#xD;
      followed by lumbar paravertebral massage maneuvers for 30 seconds. These two stimulation&#xD;
      maneuvers will be repeated until micturition begins, or for a maximum of of 3 minutes.&#xD;
&#xD;
      However, the investigators do not have data on the bacterial contamination rate for urine&#xD;
      sample using this new technique. the investigators hypothesize that the bladder stimulation&#xD;
      is a technique for obtaining urine with a contamination rate equivalent to those obtained by&#xD;
      bladder catheterization, in the diagnosis of febrile urinary tract infection in infants under&#xD;
      6 months of age.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 12, 2019</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bacterial contamination rates of urine samples per bladder stimulation and urinary catheterization</measure>
    <time_frame>at 48 hours after inclusion date</time_frame>
    <description>Bacterial contamination of urine sample is defined by:&#xD;
the growth of two or more micro-organisms,&#xD;
or the presence of a non-uropathogenic germ (lactobacilli, Staphylococcus Coagulase negative, Corynebacterium),&#xD;
or a bacteriuria&gt; 0 colony forming unit(CFU)/ml but &lt;104 CFU / ml for bladder catheterization and &lt;105 CFU / ml for clean catch urine collected by bladder stimulation, or leukocyturia &lt;104 / ml</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain of bladder stimulation</measure>
    <time_frame>through intervention completion, an average 30 min</time_frame>
    <description>pain is measured by Evaluation ENfant DOuLeur (EVENDOL) scale while the technique is performed. EVENDOL is a pain scale for children under 7. A pain scale validated for children from birth to 7 years. Score ranges from 0 to 15. Treatment threshold: 4/15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain of bladder catheterization</measure>
    <time_frame>through intervention completion, an average 30 min</time_frame>
    <description>pain is measured by Evaluation ENfant DOuLeur (EVENDOL) scale while the technique is performed. EVENDOL is a pain scale for children under 7. A pain scale validated for children from birth to 7 years. Score ranges from 0 to 15. Treatment threshold: 4/15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic performance of the dipstick urine test</measure>
    <time_frame>through intervention completion, an average 30 min</time_frame>
    <description>The diagnostic performance of the urinary dipstick will be established through sensitivity , specificity, positive predictive value and negative predictive value taking as Gold Standard cytobacteriological examination of the urine (ECBU). Diagnostic performance, as well as accuracy, will be established in each of the two groups.&#xD;
The sensitivity and specificity will be calculated as well as their 95% confidence intervals calculated using the method of the Wilson score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Risk factors associated with the failure of the bladder stimulation technique</measure>
    <time_frame>through intervention completion, an average 30 min</time_frame>
    <description>for a urinary sample quantity &lt; 2 ml or no urinary sample collected; potential risk factors for failure will be collected (pain, Wight, sex, age, last food and time since las collect urine)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">770</enrollment>
  <condition>Urinary Tract Infection Bacterial</condition>
  <arm_group>
    <arm_group_label>Urinary catheterization</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>manual bladder stimulation Technique</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>urinary catheterization</intervention_name>
    <description>Urinary catheterization with pain controlled</description>
    <arm_group_label>Urinary catheterization</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>manual bladder stimulation technique</intervention_name>
    <description>manual gentle tapping in the suprapubic area at a frequency of 100 taps per minute for 30 seconds followed by lumbar paravertebral massage maneuvers for 30 seconds. The renal and bladder stimulation will be performed in less than 3 minutes, with a maximum of two attempts spaced about 20 minutes</description>
    <arm_group_label>manual bladder stimulation Technique</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants under the age of 6 months&#xD;
&#xD;
          -  For whom an urine sample is required for the diagnosis of a urinary tract infection as&#xD;
             follows:&#xD;
&#xD;
               -  fever &gt; 39 °C without symptoms&#xD;
&#xD;
               -  fever &gt; 38°C and uropathy or urinary tract infection&#xD;
&#xD;
               -  fever &gt; 38°C and &lt; 3 months&#xD;
&#xD;
               -  fever &gt; 38 °C and &gt; 48h&#xD;
&#xD;
               -  fever &gt; 38 °C with sepsis signs&#xD;
&#xD;
          -  Obtaining the authorization of the holders of parental authority&#xD;
&#xD;
          -  Affiliation to French social security&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Do exhibiting signs of vital distress (respiratory or circulatory or neurological)&#xD;
&#xD;
          -  contraindication to bladder catheterization&#xD;
&#xD;
          -  antibiotic therapy in the last 48 hours&#xD;
&#xD;
          -  antibiotic prophylaxis in the last 48 hours&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>DEMONCHY DIANE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondation Lenval - Nice Children Hôpitaux Pédiatriques de Nice</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>DEMONCHY DIANE, MD</last_name>
    <phone>+33(0)492030502</phone>
    <email>demonchy.d@pediatrie-chulenval-nice.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>TRAN ANTOINE, MD</last_name>
    <email>tran.a@pediatrie-chulenval-nice.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CH Antibes Juans les Pins</name>
      <address>
        <city>Antibes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clara Fortier, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CH Grasse</name>
      <address>
        <city>Grasse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan Desmontils, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François Dubos, Pr</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpitaux Pédiatriques de Nice CHU-Lenval</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Demonchy Diane</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>July 26, 2022</last_update_submitted>
  <last_update_submitted_qc>July 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Urine Specimen Collection/methods</keyword>
  <keyword>Infant</keyword>
  <keyword>Newborn</keyword>
  <keyword>Feasibility Studies</keyword>
  <keyword>Bladder stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Urinary Tract Infections</mesh_term>
    <mesh_term>Bacterial Infections</mesh_term>
  </condition_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/NCT03801213
org study id: 18-HPNCL-03
nct id: NCT03801213
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Urinary tract infection (UTI) is the most common serious bacterial infection among infants.
      Suprapubic aspiration and bladder catheterization are considered as the gold standard by the
      American Academy of Pediatrics for the diagnosis, yet it is painful and invasive. In
      contrast, the bladder stimulation technique has been shown to be a quick and non-invasive
      approach to collect urine in young infants. Actually, the investigators don't have data on
      bacterial contamination rates for clean-catch midstream urine collections using this
      technique
Urinary tract infection (UTI) is common in infants and needs to be diagnosed quickly. The
      risk for urinary tract infection before the age of 2 years is about 1-4% in boys and 3-8% in
      girls. A delay in diagnosis exposes to severe complications. In infants, the symptoms are not
      specific. A good urinalysis quality is therefore necessary for the diagnosis of UTI.
      Different techniques exist to collect urine samples in these children who do not control
      their urination yet: supra pubic aspiration, catheterization, urine collection bag and clean
      catch urine. The American Academy of Pediatrics (AAP) recommends supra pubic aspiration (1-9
      % bacterial contamination) and urinary catheterization (8-14 % contamination) for collecting
      urine but these techniques are invasive and painful. The sterile bag is a non-invasive method
      of urine collection, with a high bacterial contamination rates (26-62%) leading to
      unnecessary antibiotic treatment. Finally, clean catch urine is an accepted urine sample to
      diagnose UTI according to the recommendations (13-27 % of bacterial contamination) but this
      method is only possible for potty-trained children. Recent studies (Herreros et al, Altuntas
      et al, Tran et al.) have shown that bladder stimulation, which consists of pubic tapping and
      lumbar massage, would be a new, effective, non-invasive and safe method of collecting urine
      in infants.

      Bladder stimulation may be performed by a nurse or a physician. The steps of the bladder
      stimulation technique are as follows: (a) cleaning the genital area with warm water and soap
      b) bladder stimulation technique, requires the presence of 3 people: infants will be held
      under their armpits by a parent over the bed, with legs dangling in males and hips flexed in
      females. The nurse or technician will then alternate between bladder stimulation maneuvers:
      gentle tapping in the suprapubic area at a frequency of 100 taps per minute for 30 seconds
      followed by lumbar paravertebral massage maneuvers for 30 seconds. These two stimulation
      maneuvers will be repeated until micturition begins, or for a maximum of of 3 minutes.

      However, the investigators do not have data on the bacterial contamination rate for urine
      sample using this new technique. the investigators hypothesize that the bladder stimulation
      is a technique for obtaining urine with a contamination rate equivalent to those obtained by
      bladder catheterization, in the diagnosis of febrile urinary tract infection in infants under
      6 months of age.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Bacterial contamination rates of urine samples per bladder stimulation and urinary catheterization
time frame: at 48 hours after inclusion date
description: Bacterial contamination of urine sample is defined by:
the growth of two or more micro-organisms,
or the presence of a non-uropathogenic germ (lactobacilli, Staphylococcus Coagulase negative, Corynebacterium),
or a bacteriuria> 0 colony forming unit(CFU)/ml but <104 CFU / ml for bladder catheterization and <105 CFU / ml for clean catch urine collected by bladder stimulation, or leukocyturia <104 / ml
measure: Pain of bladder stimulation
time frame: through intervention completion, an average 30 min
description: pain is measured by Evaluation ENfant DOuLeur (EVENDOL) scale while the technique is performed. EVENDOL is a pain scale for children under 7. A pain scale validated for children from birth to 7 years. Score ranges from 0 to 15. Treatment threshold: 4/15.
measure: Pain of bladder catheterization
time frame: through intervention completion, an average 30 min
description: pain is measured by Evaluation ENfant DOuLeur (EVENDOL) scale while the technique is performed. EVENDOL is a pain scale for children under 7. A pain scale validated for children from birth to 7 years. Score ranges from 0 to 15. Treatment threshold: 4/15.
measure: Diagnostic performance of the dipstick urine test
time frame: through intervention completion, an average 30 min
description: The diagnostic performance of the urinary dipstick will be established through sensitivity , specificity, positive predictive value and negative predictive value taking as Gold Standard cytobacteriological examination of the urine (ECBU). Diagnostic performance, as well as accuracy, will be established in each of the two groups.
The sensitivity and specificity will be calculated as well as their 95% confidence intervals calculated using the method of the Wilson score
measure: Risk factors associated with the failure of the bladder stimulation technique
time frame: through intervention completion, an average 30 min
description: for a urinary sample quantity < 2 ml or no urinary sample collected; potential risk factors for failure will be collected (pain, Wight, sex, age, last food and time since las collect urine)
arm group label: Urinary catheterization
arm group type: Active Comparator
arm group label: manual bladder stimulation Technique
arm group type: Experimental
intervention type: Device
intervention name: urinary catheterization
description: Urinary catheterization with pain controlled
arm group label: Urinary catheterization
intervention type: Procedure
intervention name: manual bladder stimulation technique
description: manual gentle tapping in the suprapubic area at a frequency of 100 taps per minute for 30 seconds followed by lumbar paravertebral massage maneuvers for 30 seconds. The renal and bladder stimulation will be performed in less than 3 minutes, with a maximum of two attempts spaced about 20 minutes
arm group label: manual bladder stimulation Technique
criteria: 
gender: All
minimum age: N/A
maximum age: 6 Months
healthy volunteers: No
last name: DEMONCHY DIANE, MD
role: Principal Investigator
affiliation: Fondation Lenval - Nice Children Hôpitaux Pédiatriques de Nice
last name: DEMONCHY DIANE, MD
phone: +33(0)492030502
email: demonchy.d@pediatrie-chulenval-nice.fr
last name: TRAN ANTOINE, MD
email: tran.a@pediatrie-chulenval-nice.fr
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Urinary Tract Infections
mesh term: Bacterial Infections