<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/NCT03230838</url>
  </required_header>
  <id_info>
    <org_study_id>7625A-034</org_study_id>
    <secondary_id>2016-004153-32</secondary_id>
    <nct_id>NCT03230838</nct_id>
  </id_info>
  <brief_title>MK-7625A Versus Meropenem in Pediatric Participants With Complicated Urinary Tract Infection (cUTI) (MK-7625A-034)</brief_title>
  <official_title>A Phase 2, Randomized, Active Comparator-Controlled, Multicenter, Double-Blind Clinical Trial to Study the Safety and Efficacy of Ceftolozane/Tazobactam (MK-7625A) Versus Meropenem in Pediatric Subjects With Complicated Urinary Tract Infection, Including Pyelonephritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the safety and tolerability of MK-7625A (ceftolozane/tazobactam)&#xD;
      compared with that of meropenem in pediatric participants with cUTI, including&#xD;
      pyelonephritis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 26, 2018</start_date>
  <completion_date type="Actual">December 3, 2020</completion_date>
  <primary_completion_date type="Actual">December 3, 2020</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With ≥1 Adverse Events (AEs)</measure>
    <time_frame>Up to Day 88</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Discontinuing Study Therapy Due to AE</measure>
    <time_frame>Up to Day 15</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit</measure>
    <time_frame>Up to Test of Cure Visit (up to 35 days)</time_frame>
    <description>Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the complicated urinary tract infection (cUTI) or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% confidence intervals (CIs) of each treatment are unstratified Wilson CIs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit</measure>
    <time_frame>Up to 48 hours after last oral dose (up to 19 days)</time_frame>
    <description>Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit</measure>
    <time_frame>Up to Test of Cure Visit (up to 35 days)</time_frame>
    <description>Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to &lt;10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit</measure>
    <time_frame>Up to 48 hours after last oral dose (up to 19 days)</time_frame>
    <description>Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to &lt;10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">134</enrollment>
  <condition>Complicated Urinary Tract Infection</condition>
  <condition>Pyelonephritis</condition>
  <arm_group>
    <arm_group_label>Ceftolozane/Tazobactam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meropenem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceftolozane/Tazobactam</intervention_name>
    <description>12 to &lt;18 years of age: Ceftolozane 1 g/dose; Tazobactam 0.5 g/dose via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days. &lt;12 years of age: Ceftolozane 20 mg/kg with Tazobactam 10 mg/kg (not to exceed Ceftolozane 1 g and Tazobactam 0.5 g) via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days.</description>
    <arm_group_label>Ceftolozane/Tazobactam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Meropenem</intervention_name>
    <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 7 to 14 days.</description>
    <arm_group_label>Meropenem</arm_group_label>
    <other_name>MERREM®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a legally acceptable representative who provides documented informed consent /&#xD;
             assent for the trial.&#xD;
&#xD;
          -  Ages from birth (defined as &gt;32 weeks gestational age and ≥7 days postnatal) to &lt;18&#xD;
             years of age.&#xD;
&#xD;
          -  Requires IV antibacterial therapy for the treatment of cUTI.&#xD;
&#xD;
          -  Have a pretreatment baseline urine culture specimen obtained within 48 hours before&#xD;
             the start of administration of the first dose of study treatment and preferably prior&#xD;
             to administration of any potentially therapeutic antibiotics.&#xD;
&#xD;
          -  Has pyuria.&#xD;
&#xD;
          -  Has clinical signs and/or symptoms of cUTI at the Screening Visit.&#xD;
&#xD;
          -  Is not of reproductive potential; but if of reproductive potential agrees to avoid&#xD;
             becoming pregnant or impregnating a partner during screening, while receiving study&#xD;
             treatment and for at least 30 days after the last dose of study treatment.&#xD;
&#xD;
          -  Female of reproductive potential is not pregnant, and not planning to become pregnant&#xD;
             within 30 days of the last day of treatment administration; and is nonlactating.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating in or has participated in an interventional clinical trial&#xD;
             with an investigational compound or device within 30 days prior to the first dose of&#xD;
             study treatment in this current trial.&#xD;
&#xD;
          -  Has previously participated in any trial of ceftolozane or ceftolozane/tazobactam or&#xD;
             has enrolled previously in the current trial and been discontinued.&#xD;
&#xD;
          -  Has a history of any moderate or severe hypersensitivity (e.g.anaphylaxis), allergic&#xD;
             reaction, or other contraindication to any of the following: β-lactam antibiotics&#xD;
             (e.g, penicillins, cephalosporins, and carbapenems), β-lactamase inhibitors (e.g.&#xD;
             tazobactam, sulbactam, clavulanic acid, avibactam), or metronidazole.&#xD;
&#xD;
          -  Has a history of a cUTI within the past 1 year prior to randomization known to be&#xD;
             caused by a pathogen resistant to either IV study treatment.&#xD;
&#xD;
          -  Has a concomitant infection at the time of randomization that requires nonstudy&#xD;
             systemic antibacterial therapy in addition to IV study treatment or oral step -down&#xD;
             therapy.&#xD;
&#xD;
          -  Has received potentially therapeutic antibacterial therapy for a duration more than 24&#xD;
             hours during the 48 hours preceding the first dose of study treatment.&#xD;
&#xD;
          -  Has any of the following: a) intractable UTI or pyelonephritis infection at baseline&#xD;
             that the Investigator anticipates would require more than 14 days of study treatment;&#xD;
             b) confirmed fungal urinary tract infection at time of randomization; c) permanent&#xD;
             indwelling bladder catheter or instrumentation including nephrostomy; d) current&#xD;
             urinary catheter that is not scheduled to be removed before the end of all study&#xD;
             treatment; e) complete, permanent obstruction of the urinary tract; f) suspected or&#xD;
             confirmed perinephric or intrarenal abscess; g) documented ileal loop reflux; h)&#xD;
             suspected or confirmed prostatitis, urethritis, or epididymitis; i) trauma to&#xD;
             pelvis/urinary tract.&#xD;
&#xD;
          -  Has moderate or severe impairment of renal function.&#xD;
&#xD;
          -  Has a seizure disorder or is anticipated to be treated with divalproex sodium or&#xD;
             valproic acid during the course of study treatment.&#xD;
&#xD;
          -  Is receiving, or is expected to receive, any prohibited medications.&#xD;
&#xD;
          -  Has any rapidly progressing disease or immediately life-threatening illness, including&#xD;
             acute hepatic failure, respiratory failure, or septic shock.&#xD;
&#xD;
          -  Has an immunocompromising condition.&#xD;
&#xD;
          -  Has a history of malignancy ≤5 years prior to signing informed consent.&#xD;
&#xD;
          -  Is planning to receive suppressive/prophylactic antibiotics with gram-negative&#xD;
             activity after completion of study treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Days</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital - Los Angeles ( Site 2509)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Orange County ( Site 2502)</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital-San Diego ( Site 2505)</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago ( Site 2519)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Our Lady of the Lake Hospital ( Site 2512)</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis Children's Hospital ( Site 2508)</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Upstate Medical University Hospital ( Site 2510)</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest Baptist Health ( Site 2520)</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College Of Medicine ( Site 2515)</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pan and Aglaia Kyriakou Children s Hospital ( Site 0780)</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Athens - Aghia Sophia Childrens Hospital ( Site 0730)</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Athens University Hospital ATTIKON ( Site 0790)</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>124 62</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General University Hospital of Larissa ( Site 0740)</name>
      <address>
        <city>Larissa</city>
        <state>Thessalia</state>
        <zip>411 10</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hippokration General Hospital of Thessaloniki ( Site 0700)</name>
      <address>
        <city>Thessaloniki</city>
        <state>Thessaloníki</state>
        <zip>546 42</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PTE AOK Klinikai Kozpont ( Site 0809)</name>
      <address>
        <city>Pecs</city>
        <state>Baranya</state>
        <zip>7623</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0804)</name>
      <address>
        <city>Szeged</city>
        <state>Csongrad</state>
        <zip>6720</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0808)</name>
      <address>
        <city>Nyiregyhaza</city>
        <state>Szabolcs-Szatmar-Bereg</state>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem ( Site 0810)</name>
      <address>
        <city>Budapest</city>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0801)</name>
      <address>
        <city>Budapest</city>
        <zip>1089</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debreceni Egyetem Klinikai Kozpont ( Site 0803)</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 1202)</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44280</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1204)</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo Leon</state>
        <zip>64710</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Pediatria ( Site 1201)</name>
      <address>
        <city>Mexico City</city>
        <zip>04530</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infantil de Mexico Federico Gomez ( Site 1203)</name>
      <address>
        <city>Mexico City</city>
        <zip>06720</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Obserwacyjno Zakazny ( Site 1606)</name>
      <address>
        <city>Bydgoszcz</city>
        <state>Kujawsko-pomorskie</state>
        <zip>85-030</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1600)</name>
      <address>
        <city>Bydgoszcz</city>
        <state>Kujawsko-pomorskie</state>
        <zip>85-094</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Zespolony im. Rydgiera ( Site 1607)</name>
      <address>
        <city>Torun</city>
        <state>Kujawsko-pomorskie</state>
        <zip>87-100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Centrum Zdrowia Matki Polki ( Site 1602)</name>
      <address>
        <city>Lodz</city>
        <state>Lodzkie</state>
        <zip>93-338</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniw. Szpital Dzieciecy w Krakowie ( Site 1609)</name>
      <address>
        <city>Krakow</city>
        <state>Malopolskie</state>
        <zip>30-663</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1608)</name>
      <address>
        <city>Lomianki</city>
        <state>Mazowieckie</state>
        <zip>05-092</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Clinic de Urgenta pentru Copii Maria Sklodowska Curie ( Site 1707)</name>
      <address>
        <city>Bucharest</city>
        <state>Bucuresti</state>
        <zip>041451</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1708)</name>
      <address>
        <city>Cluj-Napoca</city>
        <state>Cluj</state>
        <zip>400177</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Clinic de Urgenta pentru Copii Brasov ( Site 1703)</name>
      <address>
        <city>Brasov</city>
        <zip>500063</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 1706)</name>
      <address>
        <city>Bucuresti</city>
        <zip>021106</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Russian Pediatric Clinical Hospital ( Site 1808)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>119571</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St.Petersburg State Pediatric Medical University ( Site 1811)</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>194100</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smolensk Regional Clinical Hospital ( Site 1800)</name>
      <address>
        <city>Smolensk</city>
        <state>Smolenskaya Oblast</state>
        <zip>214018</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Childrens Clinical Hospital ( Site 1805)</name>
      <address>
        <city>Stavropol</city>
        <state>Stavropol Skiy Kray</state>
        <zip>355029</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Molotlegi Street ( Site 1903)</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0208</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inkosi Albert Luthuli Central Hospital ( Site 1902)</name>
      <address>
        <city>Durban</city>
        <state>Kwazulu-Natal</state>
        <zip>4091</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Red Cross War Memorial Children's Hospital ( Site 1900)</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7700</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 2200)</name>
      <address>
        <city>Adana</city>
        <zip>01330</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)</name>
      <address>
        <city>Ankara</city>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)</name>
      <address>
        <city>Eskisehir</city>
        <zip>26480</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)</name>
      <address>
        <city>Istanbul</city>
        <zip>34453</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2402)</name>
      <address>
        <city>Dnipro</city>
        <state>Dnipropetrovska Oblast</state>
        <zip>49100</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PI Kryvorizka city clinical hospital 8 ( Site 2408)</name>
      <address>
        <city>Kryvyy Rig</city>
        <state>Dnipropetrovska Oblast</state>
        <zip>50082</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2411)</name>
      <address>
        <city>Ivano-Frankivsk</city>
        <state>Ivano-Frankivska Oblast</state>
        <zip>76014</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 2410)</name>
      <address>
        <city>Kharkiv</city>
        <state>Kharkivska Oblast</state>
        <zip>61037</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kharkiv City Children Hospital 16 ( Site 2414)</name>
      <address>
        <city>Kharkiv</city>
        <state>Kharkivska Oblast</state>
        <zip>61075</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2409)</name>
      <address>
        <city>Kyiv</city>
        <state>Kyivska Oblast</state>
        <zip>01135</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2404)</name>
      <address>
        <city>Poltava</city>
        <state>Poltavska Oblast</state>
        <zip>36004</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Roilides E, Ashouri N, Bradley JS, Johnson MG, Lonchar J, Su FH, Huntington JA, Popejoy MW, Bensaci M, De Anda C, Rhee EG, Bruno CJ. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial. Pediatr Infect Dis J. 2023 Apr 1;42(4):292-298. doi: 10.1097/INF.0000000000003832. Epub 2023 Jan 23.</citation>
    <PMID>36689671</PMID>
  </results_reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <results_first_submitted>November 3, 2021</results_first_submitted>
  <results_first_submitted_qc>November 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 1, 2021</results_first_posted>
  <last_update_submitted>May 3, 2023</last_update_submitted>
  <last_update_submitted_qc>May 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Urinary Tract Infections</mesh_term>
    <mesh_term>Pyelonephritis</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>Ceftolozane</mesh_term>
    <mesh_term>Ceftolozane, tazobactam drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </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>September 14, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT03230838/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Males and females from birth (&gt;32 weeks gestational age and ≥7 days postnatal), to &lt;18 years of age with complicated urinary tract infection (cUTI), including pyelonephritis, were enrolled in this study.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Ceftolozane/Tazobactam</title>
          <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
        </group>
        <group group_id="P2">
          <title>Meropenem</title>
          <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="101"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="100"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Temperature excursion</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ceftolozane/Tazobactam</title>
          <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
        </group>
        <group group_id="B2">
          <title>Meropenem</title>
          <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</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="101"/>
            <count group_id="B2" value="33"/>
            <count group_id="B3" value="134"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.3" spread="5.3"/>
                    <measurement group_id="B2" value="5.5" spread="5.7"/>
                    <measurement group_id="B3" value="5.4" spread="5.4"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="108"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="100"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="133"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With ≥1 Adverse Events (AEs)</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.</description>
        <time_frame>Up to Day 88</time_frame>
        <population>All randomized participants who received any amount of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
          </group>
          <group group_id="O2">
            <title>Meropenem</title>
            <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With ≥1 Adverse Events (AEs)</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.</description>
          <population>All randomized participants who received any amount of study treatment.</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="100"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59"/>
                    <measurement group_id="O2" value="20"/>
                  </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>
            <groups_desc>Difference in Percentage (C/T minus Mero)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The Miettinen &amp; Nurminen method was used.</non_inferiority_desc>
            <param_type>Percentage Difference</param_type>
            <param_value>-1.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-19.7</ci_lower_limit>
            <ci_upper_limit>17.9</ci_upper_limit>
            <estimate_desc>Ceftolozane/Tazobactam (C/T) minus Meropenem (Mero)</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Discontinuing Study Therapy Due to AE</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.</description>
        <time_frame>Up to Day 15</time_frame>
        <population>All randomized participants who received any amount of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
          </group>
          <group group_id="O2">
            <title>Meropenem</title>
            <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Discontinuing Study Therapy Due to AE</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.</description>
          <population>All randomized participants who received any amount of study treatment.</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="100"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </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>
            <groups_desc>Difference in Percentage (C/T minus Mero)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The Miettinen &amp; Nurminen method was used.</non_inferiority_desc>
            <param_type>Percentage Difference</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.5</ci_lower_limit>
            <ci_upper_limit>5.5</ci_upper_limit>
            <estimate_desc>C/T minus Mero</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit</title>
        <description>Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the complicated urinary tract infection (cUTI) or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% confidence intervals (CIs) of each treatment are unstratified Wilson CIs.</description>
        <time_frame>Up to Test of Cure Visit (up to 35 days)</time_frame>
        <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
          </group>
          <group group_id="O2">
            <title>Meropenem</title>
            <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit</title>
          <description>Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the complicated urinary tract infection (cUTI) or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% confidence intervals (CIs) of each treatment are unstratified Wilson CIs.</description>
          <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.7" lower_limit="79.31" upper_limit="94.18"/>
                    <measurement group_id="O2" value="95.8" lower_limit="79.76" upper_limit="99.26"/>
                  </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>
            <groups_desc>Difference in Percentage (C/T minus Mero)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The Miettinen &amp; Nurminen method stratified by age group with Cochran- Mantel-Haenszel (CMH) weights was used. If there was a zero count in any class of the stratum, the groups with the lower count were pooled with its near age group stratum in the model.</non_inferiority_desc>
            <param_type>Percentage Difference</param_type>
            <param_value>-7.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.99</ci_lower_limit>
            <ci_upper_limit>10.05</ci_upper_limit>
            <estimate_desc>C/T minus Mero</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit</title>
        <description>Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
        <time_frame>Up to 48 hours after last oral dose (up to 19 days)</time_frame>
        <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
          </group>
          <group group_id="O2">
            <title>Meropenem</title>
            <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit</title>
          <description>Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
          <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.4" lower_limit="86.39" upper_limit="97.79"/>
                    <measurement group_id="O2" value="100.0" lower_limit="86.20" upper_limit="100.00"/>
                  </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>
            <groups_desc>Difference in Percentage (C/T minus Mero)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The Miettinen &amp; Nurminen method stratified by age group with Cochran- Mantel-Haenszel (CMH) weights was used. If there was a zero count in any class of the stratum, the groups with the lower count were pooled with its near age group stratum in the model.</non_inferiority_desc>
            <param_type>Percentage Difference</param_type>
            <param_value>-5.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-14.09</ci_lower_limit>
            <ci_upper_limit>8.88</ci_upper_limit>
            <estimate_desc>C/T minus Mero</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit</title>
        <description>Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to &lt;10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
        <time_frame>Up to Test of Cure Visit (up to 35 days)</time_frame>
        <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
          </group>
          <group group_id="O2">
            <title>Meropenem</title>
            <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit</title>
          <description>Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to &lt;10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
          <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.5" lower_limit="74.35" upper_limit="91.12"/>
                    <measurement group_id="O2" value="87.5" lower_limit="69.00" upper_limit="95.66"/>
                  </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>
            <groups_desc>Difference in Percentage (C/T minus Mero)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The Miettinen &amp; Nurminen method stratified by age group with Cochran- Mantel-Haenszel (CMH) weights was used. If there was a zero count in any class of the stratum, the groups with the lower count were pooled with its near age group stratum in the model.</non_inferiority_desc>
            <param_type>Percentage Difference</param_type>
            <param_value>-3.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.13</ci_lower_limit>
            <ci_upper_limit>17.40</ci_upper_limit>
            <estimate_desc>C/T minus Mero</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit</title>
        <description>Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to &lt;10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
        <time_frame>Up to 48 hours after last oral dose (up to 19 days)</time_frame>
        <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
        <group_list>
          <group group_id="O1">
            <title>Ceftolozane/Tazobactam</title>
            <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days</description>
          </group>
          <group group_id="O2">
            <title>Meropenem</title>
            <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit</title>
          <description>Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to &lt;10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.</description>
          <population>All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.0" lower_limit="84.55" upper_limit="96.95"/>
                    <measurement group_id="O2" value="95.8" lower_limit="79.76" upper_limit="99.26"/>
                  </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>
            <groups_desc>Difference in Percentage (C/T minus Mero)</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>The Miettinen &amp; Nurminen method stratified by age group with CMH weights was used. If there was a zero count in any class of the stratum, the groups with the lower count were pooled with its near age group stratum in the model.</non_inferiority_desc>
            <param_type>Percentage Difference</param_type>
            <param_value>-3.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.67</ci_lower_limit>
            <ci_upper_limit>13.41</ci_upper_limit>
            <estimate_desc>C/T minus Mero</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days.</time_frame>
      <desc>For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ceftolozane/Tazobactam</title>
          <description>Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered IV every 8 hours for 7-14 days.</description>
        </group>
        <group group_id="E2">
          <title>Meropenem</title>
          <description>Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.0</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="25" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="100"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="100"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Vulvovaginitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="100"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="100"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </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>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT03230838
org study id: 7625A-034
secondary id: 2016-004153-32
nct id: NCT03230838
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study aims to evaluate the safety and tolerability of MK-7625A (ceftolozane/tazobactam)
      compared with that of meropenem in pediatric participants with cUTI, including
      pyelonephritis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Participants With ≥1 Adverse Events (AEs)
time frame: Up to Day 88
description: An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
measure: Number of Participants Discontinuing Study Therapy Due to AE
time frame: Up to Day 15
description: An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
measure: Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit
time frame: Up to Test of Cure Visit (up to 35 days)
description: Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the complicated urinary tract infection (cUTI) or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% confidence intervals (CIs) of each treatment are unstratified Wilson CIs.
measure: Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit
time frame: Up to 48 hours after last oral dose (up to 19 days)
description: Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% CIs of each treatment are unstratified Wilson CIs.
measure: Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit
time frame: Up to Test of Cure Visit (up to 35 days)
description: Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to <10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.
measure: Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit
time frame: Up to 48 hours after last oral dose (up to 19 days)
description: Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to <10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.
arm group label: Ceftolozane/Tazobactam
arm group type: Experimental
description: Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days
arm group label: Meropenem
arm group type: Active Comparator
description: Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
intervention type: Drug
intervention name: Ceftolozane/Tazobactam
description: 12 to <18 years of age: Ceftolozane 1 g/dose; Tazobactam 0.5 g/dose via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days. <12 years of age: Ceftolozane 20 mg/kg with Tazobactam 10 mg/kg (not to exceed Ceftolozane 1 g and Tazobactam 0.5 g) via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days.
arm group label: Ceftolozane/Tazobactam
intervention type: Drug
intervention name: Meropenem
description: Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 7 to 14 days.
arm group label: Meropenem
other name: MERREM®
criteria: 
gender: All
minimum age: 7 Days
maximum age: 17 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
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country: Greece
country: Hungary
country: Mexico
country: Poland
country: Romania
country: Russian Federation
country: South Africa
country: Turkey
country: Ukraine
country: United States
citation: Roilides E, Ashouri N, Bradley JS, Johnson MG, Lonchar J, Su FH, Huntington JA, Popejoy MW, Bensaci M, De Anda C, Rhee EG, Bruno CJ. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial. Pediatr Infect Dis J. 2023 Apr 1;42(4):292-298. doi: 10.1097/INF.0000000000003832. Epub 2023 Jan 23.
PMID: 36689671
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Urinary Tract Infections
mesh term: Pyelonephritis
mesh term: Meropenem
mesh term: Tazobactam
mesh term: Ceftolozane
mesh term: Ceftolozane, tazobactam drug combination
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 