<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/NCT04478721</url>
  </required_header>
  <id_info>
    <org_study_id>ASTARTÉ</org_study_id>
    <secondary_id>2020-000064-39</secondary_id>
    <nct_id>NCT04478721</nct_id>
  </id_info>
  <brief_title>Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Resistant to Third Gen Cephalosporins</brief_title>
  <acronym>ASTARTÉ</acronym>
  <official_title>Randomised Controlled Trial of Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Due to Enterobacteriaceae Showing Resistance to Third Generation Cephalosporins</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Pública Andaluza para la gestión de la Investigación en Sevilla</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Spanish Network for Research in Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>SCReN Spanish research Network- CTU-HUVR</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundación Pública Andaluza para la gestión de la Investigación en Sevilla</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>
      A Phase 3, Multicenter, Randomised, Controlled, Open-Label Study to demonstrate&#xD;
      noninferiority of temocillin (unauthorized investigational medicinal product IMP in Spain,&#xD;
      but authorized in Belgium and UK) vs a carbapenem antibiotic (meropenem) in adults with&#xD;
      bacteraemia due to third-generation cephalosporin-resistant Enterobacteriaceae.&#xD;
&#xD;
      The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous&#xD;
      treatment, the sequential oral treatment is permitted if the patient meets appropriate&#xD;
      conditions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of the trial is to demonstrate the non-inferiority of temocillin (2g each 8&#xD;
      hours, intravenous) to carbapenems (meropenem 1g each 8 hours, intravenous) in terms of&#xD;
      efficacy and safety in the targeted treatment of bacteraemia due to Enterobacteriaceae&#xD;
      resistant to third-generation cephalosporins, and therefore provide evidence for the use of&#xD;
      temocillin in these infections.&#xD;
&#xD;
      The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous&#xD;
      treatment, the sequential oral treatment is permitted if the patient meets appropriate&#xD;
      conditions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 15, 2020</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>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>
    <intervention_model_description>Randomized 1.1 to temocillin: meropenem</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with a &quot;success&quot; at the test of cure (TOC)</measure>
    <time_frame>Up to 7-10 days after the last day of antibiotic therapy</time_frame>
    <description>A success at the test of cure is the resolution of infection symptoms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Survival at day 28</measure>
    <time_frame>At day 28.</time_frame>
    <description>Number of patients who are alive</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients who do not need to stop or change the assigned drug</measure>
    <time_frame>Up to 7-14 days after the last day of antibiotic therapy</time_frame>
    <description>Reasons for not change can be no adverse event, no perceived failure during treatment or no occurrence of a superimposed infection.&#xD;
Participants who stop or change the assigned drug will not meet the primary outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients who do not need to prolong therapy beyond 14 days</measure>
    <time_frame>Up to 7-14 days after the last day of antibiotic therapy</time_frame>
    <description>Assigned treatment to be administered for less than 14 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Not recurrence until day 28</measure>
    <time_frame>At day 28.</time_frame>
    <description>Recurrence is reappearance of symptoms with positive blood culture for the same microorganism.&#xD;
Participants with recurrence will not meet the primary outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>Up to day 28.</time_frame>
    <description>Number of patients dead up to day 28.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay (days)</measure>
    <time_frame>Through study completion, an average of 28 days</time_frame>
    <description>Number of days patients has been in-hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of intravenous therapy (days)</measure>
    <time_frame>From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days</time_frame>
    <description>Number of days patients has been under intravenous antibiotic treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of total administration of therapy (days)</measure>
    <time_frame>From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days</time_frame>
    <description>Number of days patients has been under intravenous or oral antibiotic treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with resistance development during therapy</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Resistance development will be measured in a positive blood culture</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence rate</measure>
    <time_frame>Up to day 28.</time_frame>
    <description>Percentage of subjects with recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Sequential Organ failure (SOFA) score</measure>
    <time_frame>At days 1, 3, end of treatment (days 7-14) and visit 4</time_frame>
    <description>Sequential Organ failure (SOFA) score changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old</measure>
    <time_frame>At days 1, 3, end of treatment (days 7-14) and visit 4</time_frame>
    <description>Barthel Index for Activities of Daily Living (ADL) score changes; score from 0, completely dependent patient to 100, completely independent for activities of daily living</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Peak Plasma Concentration (Cmax) of temocillin</measure>
    <time_frame>At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3</time_frame>
    <description>Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine maximum plasma levels of temocillin</description>
  </other_outcome>
  <other_outcome>
    <measure>Minimum Plasma Concentration (Cmin) of temocillin</measure>
    <time_frame>At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3</time_frame>
    <description>Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine minimum plasma levels of temocillin</description>
  </other_outcome>
  <other_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of temocillin</measure>
    <time_frame>At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3</time_frame>
    <description>Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine area under curve of temocillin</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">334</enrollment>
  <condition>Bacteremia</condition>
  <arm_group>
    <arm_group_label>Temocillin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meropenem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temocillin</intervention_name>
    <description>The intervention of experimental arm will be Intravenous administration of temocillin.</description>
    <arm_group_label>Temocillin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Meropenem</intervention_name>
    <description>The intervention of comparator arm will be intravenous administration of meropenem.</description>
    <arm_group_label>Meropenem</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with monomicrobial bacteremia due to Enterobacteriaceae showing&#xD;
             resistance to cefotaxime, ceftriaxone (MIC &gt;2 mg/L) and/or ceftazidime (MIC &gt;4 mg/L),&#xD;
             and sensible to temocillin (MIC ≤8 mg/L, except in bacteremia only of urinary origin,&#xD;
             for which the criterion is MIC ≤16 mg/L ) and meropenem (MIC ≤2 mg/L).&#xD;
&#xD;
          -  Duration of intravenous treatment is planned to be at least 4 days.&#xD;
&#xD;
          -  The patient signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt;18 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Palliative care&#xD;
&#xD;
          -  Allergy to betalactams&#xD;
&#xD;
          -  Polymicrobial bacteraemia&#xD;
&#xD;
          -  Infections typically needing prolonged &gt;14 days of therapy (e.g., endocarditis,&#xD;
             prosthetic joint infection, vascular graft infection, empyema, chronic prostatitis) or&#xD;
             meningitis&#xD;
&#xD;
          -  Active empirical treatment&gt; 96 hours after initial blood culture extraction&#xD;
&#xD;
          -  Delay in inclusion&gt; 48 h&#xD;
&#xD;
          -  Recruited in another clinical trial with active treatment&#xD;
&#xD;
          -  Peritoneal dialysis or continuous hemofiltration&#xD;
&#xD;
          -  extreme gravity or imminent death&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jesús Rodriguez Baño</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Virgen Macarena</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Clara Rosso</last_name>
    <phone>+34955013414</phone>
    <email>claram.rosso@juntadeandalucia.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Irene Borreguero</last_name>
    <phone>+34955007609</phone>
    <email>irene.borreguero@juntadeandalucia.es</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Clínico Universitario de Santiago</name>
      <address>
        <city>Santiago de Compostela</city>
        <state>A Coruña</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Hospital ParcTaulí</name>
      <address>
        <city>Sabadell</city>
        <state>Barcelona</state>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Oriol Gasch Blasi</last_name>
      <email>ogasch@tauli.cat</email>
    </contact>
    <investigator>
      <last_name>Oriol Gasch Blasi, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Mútua Terrassa</name>
      <address>
        <city>Terrassa</city>
        <state>Barcelona</state>
        <zip>08221</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Esther Calbo Sebastián</last_name>
      <email>ecalbo@mutuaterrassa.es</email>
    </contact>
    <investigator>
      <last_name>Esther Calbo Sebastián, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Cruces</name>
      <address>
        <city>Barakaldo</city>
        <state>Bizkaia</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Marqués de Valdecilla</name>
      <address>
        <city>Santander</city>
        <state>Cantabria</state>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M. Carmen Fariñas Álvarez</last_name>
      <email>mcfarinas@humv.es</email>
    </contact>
    <investigator>
      <last_name>M. Carmen Fariñas Álvarez, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Jerez de la Frontera</name>
      <address>
        <city>Jerez de la Frontera</city>
        <state>Cádiz</state>
        <zip>11407</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Salvador López Cárdenas</last_name>
      <email>salvador_lopez_cardenas@jerez.es</email>
    </contact>
    <investigator>
      <last_name>Salvador López Cárdenas, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Puerto Real</name>
      <address>
        <city>Puerto Real</city>
        <state>Cádiz</state>
        <zip>11510</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alberto Romero Palacios</last_name>
      <email>alberpalacios@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Alberto Romero Palacios, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario San Millán-San Pedro De La Rioja</name>
      <address>
        <city>Autol</city>
        <state>La Rioja</state>
        <zip>26560</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>José Antonio Oteo Revuelta</last_name>
      <phone>941298993</phone>
      <email>jaoteo@riojasalud.es</email>
    </contact>
    <investigator>
      <last_name>José Antonio Oteo Revuelta, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>José Ramón Yuste Ara</last_name>
      <email>jryuste@unav.es</email>
    </contact>
    <investigator>
      <last_name>José Ramón Yuste Ara, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario La Coruña</name>
      <address>
        <city>A Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dolores Sousa Regueiro</last_name>
      <email>Dolores.Sousa.Regueiro@sergas.es</email>
    </contact>
    <investigator>
      <last_name>Dolores Sousa Regueiro, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Alicante</name>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Esperanza Merino de Lucas</last_name>
      <email>merinoluc@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Esperanza Merino de Lucas, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Torrecárdenas</name>
      <address>
        <city>Almería</city>
        <zip>04009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M. Ángeles Esteban Moreno</last_name>
      <email>ma.esteban.moreno@gmail.com</email>
    </contact>
    <investigator>
      <last_name>M. Ángeles Esteban Moreno, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juan Pablo Horcajada Gallego</last_name>
      <phone>932483251</phone>
      <email>JHorcajada@parcdesalutmar.cat</email>
    </contact>
    <investigator>
      <last_name>Juan Pablo Horcajada Gallego, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joaquín López-Contreras González López-Contreras González</last_name>
      <email>jlcontreras@santpau.cat</email>
    </contact>
    <investigator>
      <last_name>Joaquín López-Contreras González, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofía</name>
      <address>
        <city>Córdoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ángela Cano Yuste</last_name>
      <email>cayuam@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Ángela Cano Yuste, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de las Nieves</name>
      <address>
        <city>Granada</city>
        <zip>18014</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Miguel Ángel López</last_name>
      <email>malruz@ugr.es</email>
    </contact>
    <investigator>
      <last_name>Miguel Ángel López, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Cecilio</name>
      <address>
        <city>Granada</city>
        <zip>18016</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrés Ruiz Sancho</last_name>
      <email>andresruizsancho@yahoo.es</email>
    </contact>
    <investigator>
      <last_name>Andrés Ruiz Sancho, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Juan Ramón Jiménez</name>
      <address>
        <city>Huelva</city>
        <zip>21005</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francisco Javier Martínez Marcos</last_name>
      <phone>954765204</phone>
      <email>fcojmtz@telefonica.net</email>
    </contact>
    <investigator>
      <last_name>Francisco Javier Martínez Marcos, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Jaén</name>
      <address>
        <city>Jaén</city>
        <zip>23007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Locus Augusti, Lugo</name>
      <address>
        <city>Lugo</city>
        <zip>27003</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mª José García País</last_name>
      <email>maria.jose.garcia.pais@sergas.es</email>
    </contact>
    <investigator>
      <last_name>Mª José García País, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de la Princesa</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ana Barrios Blandino</last_name>
      <email>abarrios@salud.madrid.org</email>
    </contact>
    <investigator>
      <last_name>Ana Barrios Blandino, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>María Olmedo Samperio</last_name>
      <email>maria.olmedo.samperio@gmail.com</email>
    </contact>
    <investigator>
      <last_name>María Olmedo Samperio, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rosa Escudero</last_name>
      <email>rosaescudero0@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Rosa Escudero, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario Virgen de la Arrixaca</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elisa García Vázquez, Clinico</last_name>
      <email>elisagarciavazquez@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Elisa García Vázquez, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Regional de Málaga</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lucía Valiente de Santis</last_name>
      <email>luciabvds26@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Lucía Valiente de Santis, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Enrique Nuño Álvarez</last_name>
      <email>enrique.nuno@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Enrique Nuño Álvarez, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Son Espases</name>
      <address>
        <city>Palma</city>
        <zip>07120</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>María Peñaranda Vera</last_name>
      <phone>871205371</phone>
      <email>maria.penaranda@ssib.es</email>
    </contact>
    <investigator>
      <last_name>María Peñaranda Vera, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jesús Rodríguez Baño</last_name>
      <email>jesusrb@us.es</email>
    </contact>
    <investigator>
      <last_name>Jesús Rodríguez Baño, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuel Enrique Jiménez Mejías</last_name>
      <email>mej-mejias@telefonica.net</email>
    </contact>
    <investigator>
      <last_name>Manuel Enrique Jiménez Mejías, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de Valme</name>
      <address>
        <city>Sevilla</city>
        <zip>41014</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juan Corzo Delgado</last_name>
      <email>juanecorzo@telefonica.net</email>
    </contact>
    <investigator>
      <last_name>Juan Corzo Delgado, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Vigo</name>
      <address>
        <city>Vigo</city>
        <zip>36313</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>María Teresa Pérez Rodríguez</last_name>
      <email>perezrodriguezmt@gmail.com</email>
    </contact>
    <investigator>
      <last_name>María Teresa Pérez Rodríguez, Clínico</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario Lozano Blesa</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>March 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bacteraemia</keyword>
  <keyword>Enterobacteriaceae</keyword>
  <keyword>Temocillin</keyword>
  <keyword>Third-generation cephalosporin-resistant Enterobacteriaceae.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bacteremia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meropenem</mesh_term>
    <mesh_term>Temocillin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Planning for the study will be shared with potential sites pertaining to Spanish Network for Research in Infectious Disease (REIPI)for participation. IPD is not foreseen out of this groups due to the specific characteristics of patients and sites to be candidates for study participation.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>From starting to three years of study completion planification</ipd_time_frame>
    <ipd_access_criteria>Spanish Network for Research in Infectious Disease investigators</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 4, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT04478721/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04478721
org study id: ASTARTÉ
secondary id: 2020-000064-39
nct id: NCT04478721
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A Phase 3, Multicenter, Randomised, Controlled, Open-Label Study to demonstrate
      noninferiority of temocillin (unauthorized investigational medicinal product IMP in Spain,
      but authorized in Belgium and UK) vs a carbapenem antibiotic (meropenem) in adults with
      bacteraemia due to third-generation cephalosporin-resistant Enterobacteriaceae.

      The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous
      treatment, the sequential oral treatment is permitted if the patient meets appropriate
      conditions.
The objective of the trial is to demonstrate the non-inferiority of temocillin (2g each 8
      hours, intravenous) to carbapenems (meropenem 1g each 8 hours, intravenous) in terms of
      efficacy and safety in the targeted treatment of bacteraemia due to Enterobacteriaceae
      resistant to third-generation cephalosporins, and therefore provide evidence for the use of
      temocillin in these infections.

      The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous
      treatment, the sequential oral treatment is permitted if the patient meets appropriate
      conditions.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized 1.1 to temocillin: meropenem
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with a "success" at the test of cure (TOC)
time frame: Up to 7-10 days after the last day of antibiotic therapy
description: A success at the test of cure is the resolution of infection symptoms
measure: Survival at day 28
time frame: At day 28.
description: Number of patients who are alive
measure: Number of patients who do not need to stop or change the assigned drug
time frame: Up to 7-14 days after the last day of antibiotic therapy
description: Reasons for not change can be no adverse event, no perceived failure during treatment or no occurrence of a superimposed infection.
Participants who stop or change the assigned drug will not meet the primary outcome.
measure: Number of patients who do not need to prolong therapy beyond 14 days
time frame: Up to 7-14 days after the last day of antibiotic therapy
description: Assigned treatment to be administered for less than 14 days
measure: Not recurrence until day 28
time frame: At day 28.
description: Recurrence is reappearance of symptoms with positive blood culture for the same microorganism.
Participants with recurrence will not meet the primary outcome.
measure: 28-day mortality
time frame: Up to day 28.
description: Number of patients dead up to day 28.
measure: Length of hospital stay (days)
time frame: Through study completion, an average of 28 days
description: Number of days patients has been in-hospital
measure: Length of intravenous therapy (days)
time frame: From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days
description: Number of days patients has been under intravenous antibiotic treatment
measure: Length of total administration of therapy (days)
time frame: From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days
description: Number of days patients has been under intravenous or oral antibiotic treatment
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Up to day 28
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: Number of subjects with resistance development during therapy
time frame: Up to day 28
description: Resistance development will be measured in a positive blood culture
measure: Recurrence rate
time frame: Up to day 28.
description: Percentage of subjects with recurrence
measure: Changes in Sequential Organ failure (SOFA) score
time frame: At days 1, 3, end of treatment (days 7-14) and visit 4
description: Sequential Organ failure (SOFA) score changes
measure: Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old
time frame: At days 1, 3, end of treatment (days 7-14) and visit 4
description: Barthel Index for Activities of Daily Living (ADL) score changes; score from 0, completely dependent patient to 100, completely independent for activities of daily living
measure: Peak Plasma Concentration (Cmax) of temocillin
time frame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
description: Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine maximum plasma levels of temocillin
measure: Minimum Plasma Concentration (Cmin) of temocillin
time frame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
description: Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine minimum plasma levels of temocillin
measure: Area under the plasma concentration versus time curve (AUC) of temocillin
time frame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
description: Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine area under curve of temocillin
arm group label: Temocillin
arm group type: Experimental
description: Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.
arm group label: Meropenem
arm group type: Active Comparator
description: Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.
intervention type: Drug
intervention name: Temocillin
description: The intervention of experimental arm will be Intravenous administration of temocillin.
arm group label: Temocillin
intervention type: Drug
intervention name: Meropenem
description: The intervention of comparator arm will be intravenous administration of meropenem.
arm group label: Meropenem
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jesús Rodriguez Baño
role: Principal Investigator
affiliation: Hospital Universitario Virgen Macarena
last name: Clara Rosso
phone: +34955013414
email: claram.rosso@juntadeandalucia.es
last name: Irene Borreguero
phone: +34955007609
email: irene.borreguero@juntadeandalucia.es
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Withdrawn
country: Spain
responsible party type: Sponsor
mesh term: Bacteremia
mesh term: Meropenem
mesh term: Temocillin
sharing ipd: Yes
ipd description: Planning for the study will be shared with potential sites pertaining to Spanish Network for Research in Infectious Disease (REIPI)for participation. IPD is not foreseen out of this groups due to the specific characteristics of patients and sites to be candidates for study participation.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: From starting to three years of study completion planification
ipd access criteria: Spanish Network for Research in Infectious Disease investigators
provided document: 