<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/NCT03282006</url>
  </required_header>
  <id_info>
    <org_study_id>2016-000984-18</org_study_id>
    <nct_id>NCT03282006</nct_id>
  </id_info>
  <brief_title>Treating Pyelonephritis an Urosepsis With Pivmecillinam</brief_title>
  <acronym>MePUr</acronym>
  <official_title>The Efficacy and Safety of Pivmecillinam in Treating Bacteriemic Urosepsis Caused by E.Coli</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sykehuset i Vestfold HF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Oslo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sykehuset i Vestfold HF</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 and urosepsis are common and potentially serious infections&#xD;
      that require effective antimicrobial treatment. The duration of parenteral treatment depends&#xD;
      on oral alternatives. These alternatives are few and due to antimicrobial resistance,&#xD;
      quinolones are &quot;standard of care&quot;. The increased use of quinolones is concerning because of&#xD;
      its negative ecological aspects and it is confirmed an increasing incidence of resistant&#xD;
      E.coli to quinolones in Norwegian isolates.&#xD;
&#xD;
      Pivmecillinam is an antibiotic with high susceptibility to E.coli but the evidence for&#xD;
      treating febrile urinary tract infections is insufficient. This trial will investigate the&#xD;
      efficacy and safety of pivmecillinam in treating pyelonephritis and urosepsis caused by&#xD;
      E.coli.&#xD;
&#xD;
      The hypothesis is that urosepsis can safely be treated with pivmecillinam when it is given&#xD;
      after 2-3 days with empirical i.v. antibiotics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial will be conducted at Vestfold Hospital, Norway, and is a prospective observational&#xD;
      study with intention to treat. Participants will be consecutively included among hospitalized&#xD;
      patients suffering from urosepsis - see eligibility criteria. After 3 days with parenteral&#xD;
      antibiotics, when clinical improvement and absence of fever/leukocytosis is confirmed, the&#xD;
      participants will start on pivmecillinam 400mg four times daily and be discharged.&#xD;
      Pivmecillinam is to be taken for one week. The participants will be contacted by phone on day&#xD;
      4, 10 and 33 (days after admission). On day 17 (test of cure, TOC) they will meet for&#xD;
      physical examination. They will report symptom score (standardized schema) on day 0, and 17.&#xD;
      Urine samples will be collected on day 10 and 17. Blood samples on day 17. All data will be&#xD;
      stored anonymously. The trial will be monitored by extern resources.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 29, 2017</start_date>
  <completion_date type="Actual">April 21, 2020</completion_date>
  <primary_completion_date type="Actual">April 21, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical efficacy</measure>
    <time_frame>Day 17</time_frame>
    <description>Defined as abscence of fever, no need for other antibiotics than prescribed and improvement of symptoms (self-reported improvement and EQ 5D VAS-scale).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>C-reactive protein-level (CRP)</measure>
    <time_frame>Day 17</time_frame>
    <description>Compare CRP-level on day 0 with day 17.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmission due to urinary tract infection (UTI)</measure>
    <time_frame>Day 33</time_frame>
    <description>Check if participants are readmitted due to UTI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmission - any cause</measure>
    <time_frame>Day 33</time_frame>
    <description>Check if participants have been readmitted to hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects</measure>
    <time_frame>Day 33</time_frame>
    <description>Registrate frequency of rash/skin problems, abdominal pain, clostridium difficile associated diarrhea</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbial efficacy</measure>
    <time_frame>Day 17</time_frame>
    <description>Defined as &lt;1.000 CFU E.coli in urine</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Pyelonephritis</condition>
  <condition>Urinary Tract Infections</condition>
  <arm_group>
    <arm_group_label>Pivmecillinam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with pivmecillinam</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pivmecillinam</intervention_name>
    <description>Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment</description>
    <arm_group_label>Pivmecillinam</arm_group_label>
    <other_name>Selexid, Penomax</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  E.coli in blood culture&#xD;
&#xD;
          -  AND identical isolate in urine sample (&gt;= 1.000 CFU) OR relevant clinical signs of UTI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bacterial infection origin from another organ (e.g. pneumonia)&#xD;
&#xD;
          -  Severe sepsis with multiorgan failure&#xD;
&#xD;
          -  Perinephritic abscess&#xD;
&#xD;
          -  Pyonephrosis requiring drainage&#xD;
&#xD;
          -  Allergy to pivmecillinam&#xD;
&#xD;
          -  E.coli isolate resistant to pivmecillinam&#xD;
&#xD;
          -  Pregnancy/breastfeeding&#xD;
&#xD;
          -  Severe neutropenia&#xD;
&#xD;
          -  Prostatitis&#xD;
&#xD;
          -  Severe kidney failure (eGFR&lt;15 ml/min)&#xD;
&#xD;
          -  Using valproate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>110 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tore Stenstad, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Hospital of Vestfold</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vestfold Hospital Trust</name>
      <address>
        <city>Tønsberg</city>
        <state>Vestfold</state>
        <zip>3103</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>April 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>April 21, 2020</last_update_submitted>
  <last_update_submitted_qc>April 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sykehuset i Vestfold HF</investigator_affiliation>
    <investigator_full_name>Tore Stenstad</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Pivmecillinam</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Tract Infections</mesh_term>
    <mesh_term>Pyelonephritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amdinocillin Pivoxil</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>April 21, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03282006
org study id: 2016-000984-18
nct id: NCT03282006
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Febrile urinary tract infections and urosepsis are common and potentially serious infections
      that require effective antimicrobial treatment. The duration of parenteral treatment depends
      on oral alternatives. These alternatives are few and due to antimicrobial resistance,
      quinolones are "standard of care". The increased use of quinolones is concerning because of
      its negative ecological aspects and it is confirmed an increasing incidence of resistant
      E.coli to quinolones in Norwegian isolates.

      Pivmecillinam is an antibiotic with high susceptibility to E.coli but the evidence for
      treating febrile urinary tract infections is insufficient. This trial will investigate the
      efficacy and safety of pivmecillinam in treating pyelonephritis and urosepsis caused by
      E.coli.

      The hypothesis is that urosepsis can safely be treated with pivmecillinam when it is given
      after 2-3 days with empirical i.v. antibiotics.
This trial will be conducted at Vestfold Hospital, Norway, and is a prospective observational
      study with intention to treat. Participants will be consecutively included among hospitalized
      patients suffering from urosepsis - see eligibility criteria. After 3 days with parenteral
      antibiotics, when clinical improvement and absence of fever/leukocytosis is confirmed, the
      participants will start on pivmecillinam 400mg four times daily and be discharged.
      Pivmecillinam is to be taken for one week. The participants will be contacted by phone on day
      4, 10 and 33 (days after admission). On day 17 (test of cure, TOC) they will meet for
      physical examination. They will report symptom score (standardized schema) on day 0, and 17.
      Urine samples will be collected on day 10 and 17. Blood samples on day 17. All data will be
      stored anonymously. The trial will be monitored by extern resources.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical efficacy
time frame: Day 17
description: Defined as abscence of fever, no need for other antibiotics than prescribed and improvement of symptoms (self-reported improvement and EQ 5D VAS-scale).
measure: C-reactive protein-level (CRP)
time frame: Day 17
description: Compare CRP-level on day 0 with day 17.
measure: Readmission due to urinary tract infection (UTI)
time frame: Day 33
description: Check if participants are readmitted due to UTI.
measure: Readmission - any cause
time frame: Day 33
description: Check if participants have been readmitted to hospital
measure: Adverse effects
time frame: Day 33
description: Registrate frequency of rash/skin problems, abdominal pain, clostridium difficile associated diarrhea
measure: Microbial efficacy
time frame: Day 17
description: Defined as <1.000 CFU E.coli in urine
arm group label: Pivmecillinam
arm group type: Experimental
description: Patients treated with pivmecillinam
intervention type: Drug
intervention name: pivmecillinam
description: Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment
arm group label: Pivmecillinam
other name: Selexid, Penomax
criteria: 
gender: All
minimum age: 18 Years
maximum age: 110 Years
healthy volunteers: No
last name: Tore Stenstad, MD, PhD
role: Principal Investigator
affiliation: The Hospital of Vestfold
facility: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Sykehuset i Vestfold HF
investigator full name: Tore Stenstad
investigator title: MD, PhD
mesh term: Urinary Tract Infections
mesh term: Pyelonephritis
mesh term: Amdinocillin Pivoxil
submitted: April 21, 2023