<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/NCT03019965</url>
  </required_header>
  <id_info>
    <org_study_id>2016-785-099</org_study_id>
    <nct_id>NCT03019965</nct_id>
  </id_info>
  <brief_title>Efficacy of Betalactam Antibiotics in Prolonged Infusion Compared to Intermittent in Pediatric Patients With Sepsis</brief_title>
  <official_title>Efficacy and Safety of the Administration of Betalactam Antibiotics in Continuous or Extended Infusion Compared to Intermittent Infusion in Patients With Sepsis in Two Pediatric Third-level Care Hospitals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Coordinación de Investigación en Salud, Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Instituto Mexicano del Seguro Social</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Infantil de Mexico Federico Gomez</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Regional de Alta Especialidad del Bajio</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Coordinación de Investigación en Salud, Mexico</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the efficacy and safety of the administration of betalactam antibiotics&#xD;
      in prolonged infusion compared to intermittent infusion in children with sepsis. Half of&#xD;
      participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or&#xD;
      extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or&#xD;
      meropenem in intermittent infusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally.&#xD;
      Betalactams are time-dependent antibiotics, and so, the duration of time for which the free&#xD;
      drug plasma concentration remains above the minimum inhibitory concentration (fT &gt; MIC) is&#xD;
      the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical&#xD;
      improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24&#xD;
      hours) and extended infusion (through prolonging the infusion time to greater than 3 hours)&#xD;
      allows the maintenance of concentrations above the MIC for a longer period of time within the&#xD;
      dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties&#xD;
      of betalactams and maximises bacterial killing, therefore potentially improving clinical&#xD;
      outcomes. In adult patients, the several studies suggest that prolonged infusion may offer&#xD;
      clinical benefits and significant reduction in mortality without increasing the risk of&#xD;
      toxicity, however, there is limited information about these dosing strategies in pediatric&#xD;
      patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">January 30, 2020</completion_date>
  <primary_completion_date type="Actual">December 30, 2019</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Clinical Response</measure>
    <time_frame>Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.</time_frame>
    <description>Resolution. Disappearance of all signs and symptoms related to the infection.&#xD;
Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.</time_frame>
    <description>Any harmful, undesirable, potentially serious and life threatening effects occurring during or after administration of the antibiotics proposed in this study (piperacillin / tazobactam, imipenem or meropenem), was evaluated as: none or adverse event classified according to the intensity of the clinical manifestation (severity) as: mild, moderate or severe and for each antibiotic.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">426</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Intermittent Piperacillin/tazobactam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous Piperacillin/tazobactam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermittent Imipenem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Extended Imipenem</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermittent Meropenem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Extended Meropenem</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent Piperacillin/tazobactam</intervention_name>
    <description>Piperacillin/tazobactam administered in 30 minutes infusion.</description>
    <arm_group_label>Intermittent Piperacillin/tazobactam</arm_group_label>
    <other_name>Intermittent Infusion of Piperacillin/tazobactam</other_name>
    <other_name>PiSA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous Piperacillin/tazobactam</intervention_name>
    <description>Piperacillin/tazobactam administered in 24 hours infusion.</description>
    <arm_group_label>Continuous Piperacillin/tazobactam</arm_group_label>
    <other_name>Continuous Infusion of Piperacillin/tazobactam</other_name>
    <other_name>PiSA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent Imipenem</intervention_name>
    <description>Imipenem administered in 60 minutes infusion.</description>
    <arm_group_label>Intermittent Imipenem</arm_group_label>
    <other_name>Intermittent Infusion of Imipenem</other_name>
    <other_name>PiSA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Extended Imipenem</intervention_name>
    <description>Imipenem administered in 6 hours infusion.</description>
    <arm_group_label>Extended Imipenem</arm_group_label>
    <other_name>Extended Infusion of Imipenem</other_name>
    <other_name>PiSA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent Meropenem</intervention_name>
    <description>Meropenem administered in 60 minutes infusion.</description>
    <arm_group_label>Intermittent Meropenem</arm_group_label>
    <other_name>Intermittent Infusion of Meropenem</other_name>
    <other_name>Kener</other_name>
    <other_name>Merrem, AstraZeneca</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Extended Meropenem</intervention_name>
    <description>Meropenem administered in 8 hours infusion.</description>
    <arm_group_label>Extended Meropenem</arm_group_label>
    <other_name>Extended Infusion of Meropenem</other_name>
    <other_name>Kener</other_name>
    <other_name>Merrem, AstraZeneca</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with sepsis, who have been evaluated by an infectious physician and&#xD;
             are candidates to receive piperacillin/tazobactam, imipenem or meropenem as empiric&#xD;
             treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a history of allergy to one or more of the proposed antibiotics.&#xD;
&#xD;
          -  Patients with chronic kidney disease or acute renal failure.&#xD;
&#xD;
          -  Patients with acute liver failure of any cause.&#xD;
&#xD;
          -  Patients in palliative or supportive care only.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yazmín del Carmen Fuentes</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Mexicano del Seguro Social</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Infantil de México Federico Gómez</name>
      <address>
        <city>Mexico</city>
        <state>Distrito Federal</state>
        <zip>06720</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Mexicano del Seguro Social</name>
      <address>
        <city>Mexico</city>
        <state>Distrito Federal</state>
        <zip>06720</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>December 26, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>May 29, 2021</results_first_submitted>
  <results_first_submitted_qc>July 14, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 5, 2021</results_first_posted>
  <last_update_submitted>July 14, 2021</last_update_submitted>
  <last_update_submitted_qc>July 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Coordinación de Investigación en Salud, Mexico</investigator_affiliation>
    <investigator_full_name>Yazmín Del Carmen Fuentes Pacheco</investigator_full_name>
    <investigator_title>Pediatric Infectious Disease</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meropenem</mesh_term>
    <mesh_term>Tazobactam</mesh_term>
    <mesh_term>Piperacillin</mesh_term>
    <mesh_term>Imipenem</mesh_term>
    <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Identified individual participant data for all primary and secondary outcome measures will be made available within six months of study completion</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03019965/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>the pre-specified intent was to only compare &quot;Intermittent&quot; and &quot;Prolonged&quot; Arm/Groups with the grouping of betalactam antibiotics (imipenem, meropenem and piperacillin/tazobactam)</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intermittent. Piperacillin/Tazobactam, Imipenem, Meropenem</title>
          <description>Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.&#xD;
Intermittent Piperacillin/tazobactam: Piperacillin/tazobactam administered in 30 minutes infusion.&#xD;
Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.&#xD;
Intermittent Imipenem: Imipenem administered in 60 minutes infusion. Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.&#xD;
Intermittent Meropenem: Meropenem administered in 60 minutes infusion.</description>
        </group>
        <group group_id="P2">
          <title>Prolonged Infusion. Continuous Piperacillin/Tazobactam, Extended Imipenem, Extended Meropenem</title>
          <description>Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.&#xD;
Continuous Piperacillin/tazobactam: Piperacillin/tazobactam administered in 24 hours infusion.&#xD;
Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Imipenem: Imipenem administered in 6 hours infusion.&#xD;
Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Meropenem: Meropenem administered in 8 hours infusion.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="211"/>
                <participants group_id="P2" count="215"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="201"/>
                <participants group_id="P2" count="202"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>viral or fungal infection</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>acute liver failure in the first 24 hours of randomization</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intermittent. Piperacillin/Tazobactam, Imipenem, Meropenem</title>
          <description>Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.&#xD;
Intermittent Piperacillin/tazobactam: Piperacillin/tazobactam administered in 30 minutes infusion.&#xD;
Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.&#xD;
Intermittent Imipenem: Imipenem administered in 60 minutes infusion.&#xD;
Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.&#xD;
Intermittent Meropenem: Meropenem administered in 60 minutes infusion.</description>
        </group>
        <group group_id="B2">
          <title>Prolonged Infusion. Continuous Piperacillin/Tazobactam, Extended Imipenem, Extended Meropenem</title>
          <description>Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.&#xD;
Continuous Piperacillin/tazobactam: Piperacillin/tazobactam administered in 24 hours infusion.&#xD;
Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Imipenem: Imipenem administered in 6 hours infusion.&#xD;
Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Meropenem: Meropenem administered in 8 hours infusion.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="201"/>
            <count group_id="B2" value="202"/>
            <count group_id="B3" value="403"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="201"/>
                    <measurement group_id="B2" value="202"/>
                    <measurement group_id="B3" value="403"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6" lower_limit="0" upper_limit="17"/>
                    <measurement group_id="B2" value="6" lower_limit="0" upper_limit="17"/>
                    <measurement group_id="B3" value="6" lower_limit="0" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                    <measurement group_id="B2" value="91"/>
                    <measurement group_id="B3" value="182"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="110"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="221"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Mexico</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="201"/>
                    <measurement group_id="B2" value="202"/>
                    <measurement group_id="B3" value="403"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Comorbidity</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="196"/>
                    <measurement group_id="B2" value="187"/>
                    <measurement group_id="B3" value="383"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Comorbid conditions</title>
          <population>Comorbidity only was in 196 patients in intermittent infusion group and 187 patients in prolonged infusion group.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="196"/>
                    <count group_id="B2" value="187"/>
                    <count group_id="B3" value="383"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Neoplastic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="125"/>
                    <measurement group_id="B2" value="133"/>
                    <measurement group_id="B3" value="258"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Gastrointestinal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Neurological</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Neonatal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Cardiovascular</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Respiratory</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hematologic/immunologic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Metabolic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Renal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Genetic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stem cell transplant</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hospital stay prior to enrollment to the study protocol</title>
          <description>number of participants who had been hospitalized for at least 24 hours prior to enrollment to the study protocol</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="113"/>
                    <measurement group_id="B2" value="122"/>
                    <measurement group_id="B3" value="235"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>septic shock at enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>B-lactam antibiotic</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>piperacillin/tazobactam</title>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                    <measurement group_id="B2" value="108"/>
                    <measurement group_id="B3" value="217"/>
                  </measurement_list>
                </category>
                <category>
                  <title>imipenem</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>meropenem</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>type of infection</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>febrile neutropenia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>intraabdominal</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="95"/>
                  </measurement_list>
                </category>
                <category>
                  <title>respiratory tract</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>bacteremia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>skin and soft tissue</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>urinary tract</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of participants with organisms identified</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="201"/>
                    <count group_id="B2" value="202"/>
                    <count group_id="B3" value="403"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                    <measurement group_id="B2" value="86"/>
                    <measurement group_id="B3" value="161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Clinical Response</title>
        <description>Resolution. Disappearance of all signs and symptoms related to the infection.&#xD;
Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).</description>
        <time_frame>Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.</time_frame>
        <population>The efficacy of the maneuver was evaluated by frequency of clinical response and calculation of the absolute risk reduction and the number needed to treat.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent. Piperacillin/Tazobactam, Imipenem, Meropenem</title>
            <description>Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.&#xD;
Intermittent Piperacillin/tazobactam: Piperacillin/tazobactam administered in 30 minutes infusion.&#xD;
Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.&#xD;
Intermittent Imipenem: Imipenem administered in 60 minutes infusion.&#xD;
Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.&#xD;
Intermittent Meropenem: Meropenem administered in 60 minutes infusion.</description>
          </group>
          <group group_id="O2">
            <title>Prolonged Infusion. Continuous Piperacillin/Tazobactam, Extended Imipenem, Extended Meropenem</title>
            <description>Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.&#xD;
Continuous Piperacillin/tazobactam: Piperacillin/tazobactam administered in 24 hours infusion.&#xD;
Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Imipenem: Imipenem administered in 6 hours infusion.&#xD;
Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Meropenem: Meropenem administered in 8 hours infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinical Response</title>
          <description>Resolution. Disappearance of all signs and symptoms related to the infection.&#xD;
Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).</description>
          <population>The efficacy of the maneuver was evaluated by frequency of clinical response and calculation of the absolute risk reduction and the number needed to treat.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="201"/>
                <count group_id="O2" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="178"/>
                    <measurement group_id="O2" value="169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.156</p_value>
            <method>Chi-squared</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>0.95</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.87</ci_lower_limit>
            <ci_upper_limit>1.02</ci_upper_limit>
            <other_analysis_desc>The efficacy of the maneuver was evaluated by calculating the absolute risk reduction and the number needed to treat.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Any harmful, undesirable, potentially serious and life threatening effects occurring during or after administration of the antibiotics proposed in this study (piperacillin / tazobactam, imipenem or meropenem), was evaluated as: none or adverse event classified according to the intensity of the clinical manifestation (severity) as: mild, moderate or severe and for each antibiotic.</description>
        <time_frame>Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.</time_frame>
        <population>evaluation of the safety of the intervention with analysis of the frequency of adverse events by treatment group</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent. Piperacillin/Tazobactam, Imipenem, Meropenem</title>
            <description>Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.&#xD;
Intermittent Piperacillin/tazobactam: Piperacillin/tazobactam administered in 30 minutes infusion.&#xD;
Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.&#xD;
Intermittent Imipenem: Imipenem administered in 60 minutes infusion.&#xD;
Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.&#xD;
Intermittent Meropenem: Meropenem administered in 60 minutes infusion.</description>
          </group>
          <group group_id="O2">
            <title>Prolonged Infusion. Continuous Piperacillin/Tazobactam, Extended Imipenem, Extended Meropenem</title>
            <description>Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.&#xD;
Continuous Piperacillin/tazobactam: Piperacillin/tazobactam administered in 24 hours infusion.&#xD;
Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Imipenem: Imipenem administered in 6 hours infusion.&#xD;
Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Meropenem: Meropenem administered in 8 hours infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Any harmful, undesirable, potentially serious and life threatening effects occurring during or after administration of the antibiotics proposed in this study (piperacillin / tazobactam, imipenem or meropenem), was evaluated as: none or adverse event classified according to the intensity of the clinical manifestation (severity) as: mild, moderate or severe and for each antibiotic.</description>
          <population>evaluation of the safety of the intervention with analysis of the frequency of adverse events by treatment group</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="201"/>
                <count group_id="O2" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.722</p_value>
            <method>Chi-squared</method>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>2.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.31</ci_lower_limit>
            <ci_upper_limit>28.45</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>adverse events by the mode of administration: intermittent or prolonged, evaluated during the time of administration, up to an average 24 hours after administration of the antibiotics proposed.</time_frame>
      <desc>pre-specified intent was to only compare &quot;Intermittent&quot; and &quot;Prolonged&quot; Arm/Groups with the grouping of antibiotics betalactam (imipenem, meropenem and piperacillin/tazobactam)</desc>
      <group_list>
        <group group_id="E1">
          <title>Intermittent. Piperacillin/Tazobactam, Imipenem, Meropenem</title>
          <description>Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.&#xD;
Intermittent Piperacillin/tazobactam: Piperacillin/tazobactam administered in 30 minutes infusion.&#xD;
Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.&#xD;
Intermittent Imipenem: Imipenem administered in 60 minutes infusion.&#xD;
Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.&#xD;
Intermittent Meropenem: Meropenem administered in 60 minutes infusion.</description>
        </group>
        <group group_id="E2">
          <title>Prolonged Infusion. Continuous Piperacillin/Tazobactam, Extended Imipenem, Extended Meropenem</title>
          <description>Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.&#xD;
Continuous Piperacillin/tazobactam: Piperacillin/tazobactam administered in 24 hours infusion.&#xD;
Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Imipenem: Imipenem administered in 6 hours infusion.&#xD;
Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.&#xD;
Extended Meropenem: Meropenem administered in 8 hours infusion.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="202"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="202"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1.49</frequency_threshold>
        <default_vocab>Cofepris</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="202"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>moderate adverse event</sub_title>
                <description>vomiting, diarrhea</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="201"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="202"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Yazmín Fuentes</name_or_title>
      <organization>CISMexico</organization>
      <phone>55276900 ext 22462</phone>
      <email>yazmin_fuentes@hotmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03019965
org study id: 2016-785-099
nct id: NCT03019965
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study evaluates the efficacy and safety of the administration of betalactam antibiotics
      in prolonged infusion compared to intermittent infusion in children with sepsis. Half of
      participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or
      extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or
      meropenem in intermittent infusion.
Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally.
      Betalactams are time-dependent antibiotics, and so, the duration of time for which the free
      drug plasma concentration remains above the minimum inhibitory concentration (fT > MIC) is
      the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical
      improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24
      hours) and extended infusion (through prolonging the infusion time to greater than 3 hours)
      allows the maintenance of concentrations above the MIC for a longer period of time within the
      dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties
      of betalactams and maximises bacterial killing, therefore potentially improving clinical
      outcomes. In adult patients, the several studies suggest that prolonged infusion may offer
      clinical benefits and significant reduction in mortality without increasing the risk of
      toxicity, however, there is limited information about these dosing strategies in pediatric
      patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: Number of Participants With Clinical Response
time frame: Number of participants with clinical response at 14 days after antibiotic cessation, up to an average of 28 days or the day of your discharge if this occurred before 14 days after antibiotic cessation.
description: Resolution. Disappearance of all signs and symptoms related to the infection.
Failure. Insufficient lessening of the signs and symptoms of infection to qualify as improvement, including death or indeterminate (no evaluation possible, for any reason).
measure: Number of Participants With Adverse Events
time frame: Number of participants with adverse events evaluated by an physician at the time of administration of antibiotics, up to an average to 24 hours after the study drug cessation.
description: Any harmful, undesirable, potentially serious and life threatening effects occurring during or after administration of the antibiotics proposed in this study (piperacillin / tazobactam, imipenem or meropenem), was evaluated as: none or adverse event classified according to the intensity of the clinical manifestation (severity) as: mild, moderate or severe and for each antibiotic.
arm group label: Intermittent Piperacillin/tazobactam
arm group type: Active Comparator
description: Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.
arm group label: Continuous Piperacillin/tazobactam
arm group type: Experimental
description: Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.
arm group label: Intermittent Imipenem
arm group type: Active Comparator
description: Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.
arm group label: Extended Imipenem
arm group type: Experimental
description: Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.
arm group label: Intermittent Meropenem
arm group type: Active Comparator
description: Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.
arm group label: Extended Meropenem
arm group type: Experimental
description: Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.
intervention type: Drug
intervention name: Intermittent Piperacillin/tazobactam
description: Piperacillin/tazobactam administered in 30 minutes infusion.
arm group label: Intermittent Piperacillin/tazobactam
other name: Intermittent Infusion of Piperacillin/tazobactam
other name: PiSA
intervention type: Drug
intervention name: Continuous Piperacillin/tazobactam
description: Piperacillin/tazobactam administered in 24 hours infusion.
arm group label: Continuous Piperacillin/tazobactam
other name: Continuous Infusion of Piperacillin/tazobactam
other name: PiSA
intervention type: Drug
intervention name: Intermittent Imipenem
description: Imipenem administered in 60 minutes infusion.
arm group label: Intermittent Imipenem
other name: Intermittent Infusion of Imipenem
other name: PiSA
intervention type: Drug
intervention name: Extended Imipenem
description: Imipenem administered in 6 hours infusion.
arm group label: Extended Imipenem
other name: Extended Infusion of Imipenem
other name: PiSA
intervention type: Drug
intervention name: Intermittent Meropenem
description: Meropenem administered in 60 minutes infusion.
arm group label: Intermittent Meropenem
other name: Intermittent Infusion of Meropenem
other name: Kener
other name: Merrem, AstraZeneca
intervention type: Drug
intervention name: Extended Meropenem
description: Meropenem administered in 8 hours infusion.
arm group label: Extended Meropenem
other name: Extended Infusion of Meropenem
other name: Kener
other name: Merrem, AstraZeneca
criteria: 
gender: All
minimum age: 1 Month
maximum age: 17 Years
healthy volunteers: No
last name: Yazmín del Carmen Fuentes
role: Principal Investigator
affiliation: Instituto Mexicano del Seguro Social
facility: 
facility: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: Coordinación de Investigación en Salud, Mexico
investigator full name: Yazmín Del Carmen Fuentes Pacheco
investigator title: Pediatric Infectious Disease
mesh term: Sepsis
mesh term: Toxemia
mesh term: Meropenem
mesh term: Tazobactam
mesh term: Piperacillin
mesh term: Imipenem
mesh term: Piperacillin, Tazobactam Drug Combination
sharing ipd: No
ipd description: Identified individual participant data for all primary and secondary outcome measures will be made available within six months of study completion
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 