<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/NCT03280147</url>
  </required_header>
  <id_info>
    <org_study_id>5/7/329/2009-RHN</org_study_id>
    <nct_id>NCT03280147</nct_id>
  </id_info>
  <brief_title>7 Days Versus 14 Days of Antibiotics for Neonatal Sepsis</brief_title>
  <official_title>Comparison of the Efficacy of a 7-day Versus 14-day Course of Intravenous Antibiotics in the Treatment of Uncomplicated Neonatal Bacterial Sepsis: a Randomized Controlled Non-inferiority Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indian Council of Medical Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Postgraduate Institute of Medical Education and Research, Chandigarh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chacha Nehru Bal Chikitsalaya, New Delhi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lady Hardinge Medical College</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Indira Gandhi Institute of Child Health, Bangalore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute of Obstetrics and Gynecology, Chennai</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>King George's Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Indian Council of Medical Research</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>
      The optimum duration of intravenous antibiotic therapy for culture-proven neonatal bacterial&#xD;
      sepsis is not known. Current practices, ranging from 7 days to 14 days of antibiotics, are&#xD;
      not evidence-based. This is a randomized, active -controlled, multi-centric, non-inferiority&#xD;
      trial to compare the efficacy of a 7-day course of intravenous antibiotics versus a 14-day&#xD;
      course among neonates weighing &gt; 1000 g at birth with culture-proven bacterial sepsis that is&#xD;
      uncomplicated by meningitis, bone or joint infections deep-seated abscesses. The primary&#xD;
      outcome measure is a definite or probable relapse within 21 days after stoppage of&#xD;
      antibiotics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The optimum duration of intravenous antibiotic therapy for uncomplicated neonatal bacterial&#xD;
      septicemia is not known. Pediatricians administer anywhere between 7 to 14 days of&#xD;
      antibiotics, but these practices are not evidence based. C reactive protein (CRP) guided&#xD;
      antibiotic duration is based on limited data and serial quantitative CRP is both cumbersome&#xD;
      and not universally available. If it could be demonstrated that a 7-day course of antibiotics&#xD;
      is not inferior to a 14-day course of antibiotics in terms of relapse rates of infection,&#xD;
      then a 7 day course of antibiotics could be uniformly adopted, resulting in economic savings,&#xD;
      shorter duration of hospitalization, less chances of hospital acquired infections, less&#xD;
      chances of antibiotic induced adverse events and less antibiotic resistance. To test this&#xD;
      hypothesis, a randomized, active-controlled, multi-centric, non-inferiority trial to compare&#xD;
      the efficacy of a 7-day course of intravenous antibiotics with a 14-day course has been&#xD;
      planned. Subjects weighing more than 1000 g at birth with suspected sepsis will be enrolled&#xD;
      and observed for a 7-day period to see if they meet eligibility criteria for randomization.&#xD;
      Subjects will be randomized on the 7th day of antibiotics, if the initial blood culture grows&#xD;
      a non-Staphylococcus aureus bacterial organism, if they have no meningitis, osteomyelitis,&#xD;
      septic arthritis or deep seated abscess and if the sepsis goes into clinical remission by the&#xD;
      5th day and remains in remission up to the 7th day of sensitive antibiotics. Subjects in the&#xD;
      14-day group will receive 7 more days of antibiotics after randomization, whereas those in&#xD;
      the 7-day group will receive no further antibiotics after randomization. Subjects will be&#xD;
      followed up for a 35-day period after randomization. The key outcome will be treatment&#xD;
      failure as measured by &quot;definite or probable relapse&quot; within a 21-day period after completion&#xD;
      of antibiotic therapy. Secondary outcomes will include definite relapse within 21 and 28 days&#xD;
      after antibiotic completion and within 28 and 35 days after randomization; and probable&#xD;
      relapse at similar time points. Other secondary outcomes will include secondary infections&#xD;
      and adverse events. A total sample size of 700 (350 in each arm) will be required to detect a&#xD;
      non-inferiority margin of 5%, assumed event rate of 10%, with 90% power, one-sided alpha&#xD;
      error of 5% and loss to follow-up of approximately 10%. Data safety monitoring board will&#xD;
      monitor serious adverse events in the trial and will perform one mid-term analysis when about&#xD;
      50% of the expected primary outcomes have occurred or when 50% of the subjects have completed&#xD;
      their follow-up as per protocol, whichever is earlier. At the time of interim analysis, the&#xD;
      DSMB will revisit the sample size of the study. O'Brien Fleming's stopping criteria will be&#xD;
      used for the primary outcome while Pocock's stopping rule will be used for the serious&#xD;
      adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">January 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized, outcome-assessor blinded, active-controlled, multi-centric, non-inferiority trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Outcome assessor will be provided objective clinical information related to episodes of all illnesses during follow-up with all patient identifiers removed and the record identified only by a unique code number. All imaging films and investigation reports provided to the outcome assessor will be similarly bereft of patient identifiers and coded by a unique code number. The outcome assessor will not be involved in the rest of the study. The outcome assessor will adjudicate whether the given episode of illness is a relapse.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Definite or probable relapse within 21 days post-antibiotic completion as per protocol</measure>
    <time_frame>From 0-21 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among participants who adhered to study protocol- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Definite or probable relapse within 21 days post-antibiotic completion as per intention to treat</measure>
    <time_frame>From 0-21 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among all randomized patients- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 21 days post-antibiotic completion, as per protocol</measure>
    <time_frame>From 0-21 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 21 days post-antibiotic completion, as per intention-to-treat</measure>
    <time_frame>From 0-21 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 28 days post-antibiotic completion, as per protocol</measure>
    <time_frame>From 0-28 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 28 days post-antibiotic completion, as per intention-to-treat</measure>
    <time_frame>From 0-28 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 28 days post-randomization, as per protocol</measure>
    <time_frame>From 0-28 days after randomization</time_frame>
    <description>Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 28 days post-randomization, as per Intention-to-treat</measure>
    <time_frame>From 0-28 days after randomization</time_frame>
    <description>Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 35 days post-randomization, as per protocol</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse within 35 days post-randomization, as per intention to treat</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 21 days post-antibiotic completion, as per protocol</measure>
    <time_frame>From 0-21 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 21 days post-antibiotic completion, as per intention-to-treat</measure>
    <time_frame>From 0-21 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 28 days post-antibiotic completion, as per protocol</measure>
    <time_frame>From 0-28 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 28 days post-antibiotic completion, as per intention-to-treat</measure>
    <time_frame>From 0-28 days after the end of the planned antibiotic therapy</time_frame>
    <description>Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 28 days post-randomization, as per protocol</measure>
    <time_frame>From 0-28 days after randomization</time_frame>
    <description>Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 28 days post-randomization, as per intention-to-treat</measure>
    <time_frame>From 0-28 days after randomization</time_frame>
    <description>Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 35 days post-randomization, as per protocol</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probable relapse within 35 days post-randomization, as per intention-to-treat</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Among all randomised patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse or probable relapse within 28 days post-randomization, as per protocol</measure>
    <time_frame>From 0-28 days after randomization</time_frame>
    <description>Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse or probable relapse within 28 days post-randomization, as per Intention-to-treat</measure>
    <time_frame>From 0-28 days after randomization</time_frame>
    <description>Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse or probable relapse within 35 days post-randomization, as per protocol</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite relapse or probable relapse within 35 days post-randomization, as per intention-to-treat</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Among all randomised patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary sepsis</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Sepsis due to bacterial organisms other than the original etiologic bacteria or with a different antibiogram or with a fungal organism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>From 0-35 days after randomization</time_frame>
    <description>Adverse events as per a list of adverse events, graded as per severity, and defined a priori</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">750</enrollment>
  <condition>Infant, Newborn</condition>
  <condition>Neonatal SEPSIS</condition>
  <condition>Anti-bacterial Agents</condition>
  <condition>Recurrence</condition>
  <arm_group>
    <arm_group_label>7-day course of antibiotics</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 7-day group will not receive any further antibiotics.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>14-day course of antibiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 14-day group will receive 7 more days of the same antibiotics, to make it a total of 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>7-day course of antibiotics</intervention_name>
    <description>Subjects in the &quot;7-day course of antibiotics&quot; arm of the study will receive no further antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.</description>
    <arm_group_label>7-day course of antibiotics</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>14-day course of antibiotics</intervention_name>
    <description>Subjects in the &quot;14-day course of antibiotics&quot; arm of the study will receive 7 more days of antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.</description>
    <arm_group_label>14-day course of antibiotics</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria for the initial observation part of study preceding randomization&#xD;
&#xD;
          1. Neonates aged 0-28 days, either inborn or outborn, who are currently admitted in the&#xD;
             Neonatal Unit of the centre.&#xD;
&#xD;
          2. Whose birth weight is greater than 1000 grams (it should be reliably ascertained from&#xD;
             records of a hospital)&#xD;
&#xD;
          3. Whose residence is within approximately 15 kms from the center, so that the infant can&#xD;
             be brought back to the center for follow-up&#xD;
&#xD;
          4. Who have suspected septicemia for which a conventional or BACTEC/BACTALERT blood&#xD;
             culture is sent and for which the treating physician decides to start antibiotics&#xD;
&#xD;
        Inclusion criteria for Randomization applicable after 7 days of therapy of above patients&#xD;
        with sensitive antibiotics:&#xD;
&#xD;
          1. Positive blood culture other than Staphylococcus aureus&#xD;
&#xD;
          2. No signs and symptoms of sepsis from end of day 5 through end of day 7 of starting&#xD;
             sensitive antibiotics&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion criteria for the initial observation part of study preceding randomization:&#xD;
&#xD;
          1. Suspected meniingitis (meningitis will be defined as one or more of CSF cell count&#xD;
             more than or equal to 25 per microliter with &gt; 60% neutrophils; glucose 180 mg/dL in&#xD;
             preterm or positive gram stain report)&#xD;
&#xD;
          2. Septic arthritis, osteomyelitis or deep-seated abscess as clinically judged by the&#xD;
             treating team&#xD;
&#xD;
          3. Life threatening congenital malformations as judged by the principal investigator of&#xD;
             the centre&#xD;
&#xD;
        Exclusion criteria for randomization applicable after 7 days of therapy of above patients&#xD;
        with sensitive antibiotics:&#xD;
&#xD;
          1. Sterile blood culture&#xD;
&#xD;
          2. Suspected contaminants in blood culture.&#xD;
&#xD;
          3. Growth of Staphylococcus aureus in blood culture&#xD;
&#xD;
          4. Growth of fungal organism in blood culture&#xD;
&#xD;
          5. Diagnosis of meningitis, septic arthritis, osteomyelitis, abscess&#xD;
&#xD;
          6. Has not gone into remission on day 5 or have recurrence of symptoms from day 5 through&#xD;
             day 7&#xD;
&#xD;
          7. If the empiric antibiotic is resistant but neonate has shown improvement of signs and&#xD;
             symptoms of sepsis and there is ambiguity regarding in vivo sensitivity of antibiotic&#xD;
             use&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Hour</minimum_age>
    <maximum_age>28 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sourabh Dutta</last_name>
    <role>Principal Investigator</role>
    <affiliation>Postgraduate Institute of Medical Education and Research</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Reeta Rasaily</last_name>
    <phone>+91-9818635958</phone>
    <email>reeta.rasaily@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Pandit BD Sharma Postgraduate Institute of Medical Sciences</name>
      <address>
        <city>Rohtak</city>
        <state>Haryana</state>
        <zip>124001</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>St Johns Medical College Hospital</name>
      <address>
        <city>Bangalore</city>
        <state>Karnataka</state>
        <zip>560034</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Institute of Child Health</name>
      <address>
        <city>Chennai</city>
        <state>Tamil Nadu</state>
        <zip>600008</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Postgraduate Institute of Medical Education and Research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160023</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sourabh Dutta, MD, PhD</last_name>
      <phone>+91-8283831967</phone>
      <email>sourabhdutta1@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kalawati Saran Childrens Hospital and Lady Hardinge Medical College</name>
      <address>
        <city>New Delhi</city>
        <zip>110001</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sushma Nangia</last_name>
      <phone>+91-9810838181</phone>
      <email>drsnangia@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chacha Nehru Bal Chikitsalaya</name>
      <address>
        <city>New Delhi</city>
        <zip>110031</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mamta Jajoo</last_name>
      <phone>+91-9643308217</phone>
      <email>mamtajajoo123@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 9, 2017</study_first_submitted>
  <study_first_submitted_qc>September 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>March 9, 2021</last_update_submitted>
  <last_update_submitted_qc>March 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Sourabh Dutta</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Neonate</keyword>
  <keyword>Sepsis</keyword>
  <keyword>Antibiotics</keyword>
  <keyword>Duration</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Neonatal Sepsis</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Antibiotics, Antitubercular</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03280147/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03280147/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03280147
org study id: 5/7/329/2009-RHN
nct id: NCT03280147
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The optimum duration of intravenous antibiotic therapy for culture-proven neonatal bacterial
      sepsis is not known. Current practices, ranging from 7 days to 14 days of antibiotics, are
      not evidence-based. This is a randomized, active -controlled, multi-centric, non-inferiority
      trial to compare the efficacy of a 7-day course of intravenous antibiotics versus a 14-day
      course among neonates weighing > 1000 g at birth with culture-proven bacterial sepsis that is
      uncomplicated by meningitis, bone or joint infections deep-seated abscesses. The primary
      outcome measure is a definite or probable relapse within 21 days after stoppage of
      antibiotics.
The optimum duration of intravenous antibiotic therapy for uncomplicated neonatal bacterial
      septicemia is not known. Pediatricians administer anywhere between 7 to 14 days of
      antibiotics, but these practices are not evidence based. C reactive protein (CRP) guided
      antibiotic duration is based on limited data and serial quantitative CRP is both cumbersome
      and not universally available. If it could be demonstrated that a 7-day course of antibiotics
      is not inferior to a 14-day course of antibiotics in terms of relapse rates of infection,
      then a 7 day course of antibiotics could be uniformly adopted, resulting in economic savings,
      shorter duration of hospitalization, less chances of hospital acquired infections, less
      chances of antibiotic induced adverse events and less antibiotic resistance. To test this
      hypothesis, a randomized, active-controlled, multi-centric, non-inferiority trial to compare
      the efficacy of a 7-day course of intravenous antibiotics with a 14-day course has been
      planned. Subjects weighing more than 1000 g at birth with suspected sepsis will be enrolled
      and observed for a 7-day period to see if they meet eligibility criteria for randomization.
      Subjects will be randomized on the 7th day of antibiotics, if the initial blood culture grows
      a non-Staphylococcus aureus bacterial organism, if they have no meningitis, osteomyelitis,
      septic arthritis or deep seated abscess and if the sepsis goes into clinical remission by the
      5th day and remains in remission up to the 7th day of sensitive antibiotics. Subjects in the
      14-day group will receive 7 more days of antibiotics after randomization, whereas those in
      the 7-day group will receive no further antibiotics after randomization. Subjects will be
      followed up for a 35-day period after randomization. The key outcome will be treatment
      failure as measured by "definite or probable relapse" within a 21-day period after completion
      of antibiotic therapy. Secondary outcomes will include definite relapse within 21 and 28 days
      after antibiotic completion and within 28 and 35 days after randomization; and probable
      relapse at similar time points. Other secondary outcomes will include secondary infections
      and adverse events. A total sample size of 700 (350 in each arm) will be required to detect a
      non-inferiority margin of 5%, assumed event rate of 10%, with 90% power, one-sided alpha
      error of 5% and loss to follow-up of approximately 10%. Data safety monitoring board will
      monitor serious adverse events in the trial and will perform one mid-term analysis when about
      50% of the expected primary outcomes have occurred or when 50% of the subjects have completed
      their follow-up as per protocol, whichever is earlier. At the time of interim analysis, the
      DSMB will revisit the sample size of the study. O'Brien Fleming's stopping criteria will be
      used for the primary outcome while Pocock's stopping rule will be used for the serious
      adverse events.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, outcome-assessor blinded, active-controlled, multi-centric, non-inferiority trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Outcome assessor will be provided objective clinical information related to episodes of all illnesses during follow-up with all patient identifiers removed and the record identified only by a unique code number. All imaging films and investigation reports provided to the outcome assessor will be similarly bereft of patient identifiers and coded by a unique code number. The outcome assessor will not be involved in the rest of the study. The outcome assessor will adjudicate whether the given episode of illness is a relapse.
measure: Definite or probable relapse within 21 days post-antibiotic completion as per protocol
time frame: From 0-21 days after the end of the planned antibiotic therapy
description: Among participants who adhered to study protocol- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Definite or probable relapse within 21 days post-antibiotic completion as per intention to treat
time frame: From 0-21 days after the end of the planned antibiotic therapy
description: Among all randomized patients- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Definite relapse within 21 days post-antibiotic completion, as per protocol
time frame: From 0-21 days after the end of the planned antibiotic therapy
description: Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 21 days post-antibiotic completion, as per intention-to-treat
time frame: From 0-21 days after the end of the planned antibiotic therapy
description: Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 28 days post-antibiotic completion, as per protocol
time frame: From 0-28 days after the end of the planned antibiotic therapy
description: Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 28 days post-antibiotic completion, as per intention-to-treat
time frame: From 0-28 days after the end of the planned antibiotic therapy
description: Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 28 days post-randomization, as per protocol
time frame: From 0-28 days after randomization
description: Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 28 days post-randomization, as per Intention-to-treat
time frame: From 0-28 days after randomization
description: Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 35 days post-randomization, as per protocol
time frame: From 0-35 days after randomization
description: Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Definite relapse within 35 days post-randomization, as per intention to treat
time frame: From 0-35 days after randomization
description: Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
measure: Probable relapse within 21 days post-antibiotic completion, as per protocol
time frame: From 0-21 days after the end of the planned antibiotic therapy
description: Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 21 days post-antibiotic completion, as per intention-to-treat
time frame: From 0-21 days after the end of the planned antibiotic therapy
description: Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 28 days post-antibiotic completion, as per protocol
time frame: From 0-28 days after the end of the planned antibiotic therapy
description: Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 28 days post-antibiotic completion, as per intention-to-treat
time frame: From 0-28 days after the end of the planned antibiotic therapy
description: Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 28 days post-randomization, as per protocol
time frame: From 0-28 days after randomization
description: Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 28 days post-randomization, as per intention-to-treat
time frame: From 0-28 days after randomization
description: Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 35 days post-randomization, as per protocol
time frame: From 0-35 days after randomization
description: Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Probable relapse within 35 days post-randomization, as per intention-to-treat
time frame: From 0-35 days after randomization
description: Among all randomised patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Definite relapse or probable relapse within 28 days post-randomization, as per protocol
time frame: From 0-28 days after randomization
description: Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Definite relapse or probable relapse within 28 days post-randomization, as per Intention-to-treat
time frame: From 0-28 days after randomization
description: Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Definite relapse or probable relapse within 35 days post-randomization, as per protocol
time frame: From 0-35 days after randomization
description: Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Definite relapse or probable relapse within 35 days post-randomization, as per intention-to-treat
time frame: From 0-35 days after randomization
description: Among all randomised patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
measure: Secondary sepsis
time frame: From 0-35 days after randomization
description: Sepsis due to bacterial organisms other than the original etiologic bacteria or with a different antibiogram or with a fungal organism
measure: Adverse events
time frame: From 0-35 days after randomization
description: Adverse events as per a list of adverse events, graded as per severity, and defined a priori
arm group label: 7-day course of antibiotics
arm group type: Experimental
description: Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 7-day group will not receive any further antibiotics.
arm group label: 14-day course of antibiotics
arm group type: Active Comparator
description: Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 14-day group will receive 7 more days of the same antibiotics, to make it a total of 14 days.
intervention type: Drug
intervention name: 7-day course of antibiotics
description: Subjects in the "7-day course of antibiotics" arm of the study will receive no further antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.
arm group label: 7-day course of antibiotics
intervention type: Drug
intervention name: 14-day course of antibiotics
description: Subjects in the "14-day course of antibiotics" arm of the study will receive 7 more days of antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.
arm group label: 14-day course of antibiotics
criteria: 
gender: All
minimum age: 1 Hour
maximum age: 28 Days
healthy volunteers: No
last name: Sourabh Dutta
role: Principal Investigator
affiliation: Postgraduate Institute of Medical Education and Research
last name: Reeta Rasaily
phone: +91-9818635958
email: reeta.rasaily@gmail.com
facility: 
status: Terminated
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Sourabh Dutta
investigator title: Professor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Neonatal Sepsis
mesh term: Recurrence
mesh term: Anti-Bacterial Agents
mesh term: Antibiotics, Antitubercular
sharing ipd: No
provided document: 
provided document: 