<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/NCT01678365</url>
  </required_header>
  <id_info>
    <org_study_id>043-07-EMC</org_study_id>
    <nct_id>NCT01678365</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children</brief_title>
  <official_title>Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HaEmek Medical Center, Israel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>HaEmek Medical Center, Israel</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective open randomized study conducted between July 1st 2008 and June 30th, 2009.&#xD;
      Included were children younger than 14 years with Complicated appendicitis randomly assigned&#xD;
      either to a single daily dose of Ceftriaxone and Metronidazole or Ampicillin, Gentamicin, and&#xD;
      Metronidazole. The outcome variables compared were: maximum daily temperatures, overall&#xD;
      duration of fever, time return to oral intake, length of antibiotic therapy, results of&#xD;
      repeat WBC measure, general/intra abdominal complications, need for intra abdominal abscess&#xD;
      drainage, Length of stay and adverse reaction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study was conducted at the Pediatric Surgery Department at HaEmek Medical Center, Afula,&#xD;
      Israel. Included were children age 1-14 years with complicated appendicitis that was defined&#xD;
      by one of the followings: 1. Demonstration by abdominal ultrasound and/or computed tomography&#xD;
      of appendix perforation and/or peri-appendicular abscess 2. Demonstration by abdominal&#xD;
      ultrasound of free fluid, and signs of diffuse peritoneal irritation in the right lower&#xD;
      quadrant of the abdomen 3. At surgery performed for suspected non complicated appendicitis.&#xD;
      In a patient with perforate appendicitis that was diagnosed at surgery, appendectomy was&#xD;
      performed by one of the 4 senior pediatric surgeons on call at the time of the child's&#xD;
      admission. Exclusion criteria were: documented allergy to any of the study medications, acute&#xD;
      or renal insufficiency at admission, and severe septic shock at admission.&#xD;
&#xD;
      Therapeutic approach: After the diagnosis of complicated appendicitis was established,&#xD;
      patients were randomly assigned to therapy with either once daily of ceftriaxone and&#xD;
      metronidazole or ampicillin, gentamicin and metronidazole. Therapy was change to&#xD;
      piperacillin/tazobactam in patients who were still febrile at day 7-10 of the admission (if&#xD;
      not given before), based on the clinical situation, and in all febrile patients at 11 day of&#xD;
      the admission . All patients had also been treats after inclusion with pain control&#xD;
      medications, no oral food or fluid , and intravenous hydration as necessary. Nasogastric&#xD;
      tubes were not used routinely. On the fifth admission day patients who were stable, a&#xD;
      febrile, could tolerate diet and had Complete blood count within normal limits were&#xD;
      discharged home with oral amoxicillin/clavulanate therapy for further 7 days.&#xD;
&#xD;
      Follow-up at the admission: CBC and renal and liver function tests were obtained before&#xD;
      starting the antibiotic treatment and repeated on day 4 in all patients. In the group treated&#xD;
      with AGM, serum trough gentamicin concentration was drawn before the fourth dose with normal&#xD;
      level considered as &lt; 2 mcg/ml. Other blood studies were performed based on the discretion of&#xD;
      the attending physician based on the patient's clinical status. For patients who were either&#xD;
      febrile or had leukocytosis, at day 5 of therapy abdominal ultrasound was obtained to assess&#xD;
      for the presence of an abscess. Patients in whom abscesses were delectated undergone per&#xD;
      coetaneous drainage (when possible). The original antibiotic regimen was either continued or&#xD;
      changed to piperacillin/tazobactam based on the clinical situation. Patients, in whom&#xD;
      appendectomy had not been done at admission, were readmitted for appendectomy at 6 weeks. All&#xD;
      patients had been followed for a year since the admission for signs of intra abdominal&#xD;
      complication such: repeat abscess formation, repeat admission, obstruction etc.&#xD;
&#xD;
      Data collection: Data were recorded were: patient's age, weight, gender, maximum daily&#xD;
      temperature, duration of fever, results of complete blood count, renal and liver function&#xD;
      tests, gentamicin levels (where applicable), intra abdominal complications and duration of&#xD;
      hospitalization. The outcome variables included maximum daily temperatures for each of the&#xD;
      first 10 postoperative days, time to initial oral intake, length of hospitalization, length&#xD;
      of antibiotic therapy, abscess formation rate, need to change antibiotic regimen, wound&#xD;
      infection rate, and any abnormal findings during the follow-up visits.&#xD;
&#xD;
      Statistical analysis: Since data in the literature show that there is no difference of the&#xD;
      length of stay in between the 2 regimens (in children with complicated appendicitis following&#xD;
      operation), and most studies included relatively low number of patients, no power analysis&#xD;
      was calculated. The difference between various parameters in the two treatment groups were&#xD;
      assessed by 2 independent sample T tests or Fisher exact tests for categorical data and 2&#xD;
      independent sample t test or the Mann Whitney test for continuous data. Descriptive&#xD;
      statistics were calculated as mean ± SD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2008</start_date>
  <completion_date type="Actual">October 2009</completion_date>
  <primary_completion_date type="Actual">October 2009</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Length of stay (days)</measure>
    <time_frame>From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of primary antibiotic regimen to Piperacillin/tazobactam</measure>
    <time_frame>From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of new intrabdominal abcesses</measure>
    <time_frame>From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Re hospitalization due to intra abdominal abcess formation</measure>
    <time_frame>Within 2 years after day of discharge</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Complicated Appendicitis</condition>
  <arm_group>
    <arm_group_label>ceftriaxone and metronidazole for complicated appendicitis.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children with complicated appendicitis treated with single daily dose of ceftriaxone and metronidazole.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ampicillin, gentamicin, and metronidazole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Children with complicated appendicitis treated with ampicillin, gentamicin, and metronidazole</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ceftriaxone, metronidazole/ampicillin, gentamicin, and metronidazole</intervention_name>
    <arm_group_label>Ampicillin, gentamicin, and metronidazole</arm_group_label>
    <arm_group_label>ceftriaxone and metronidazole for complicated appendicitis.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children age 1-14 years CA that was defined by one of the followings:&#xD;
&#xD;
               1. Demonstration by abdominal ultrasound (US) and/or computed tomography (CT) of&#xD;
                  appendix perforation and/or peri-appendicular abscess&#xD;
&#xD;
               2. Demonstration by abdominal ultrasound (US) of free fluid, and signs of diffuse&#xD;
                  peritoneal irritation in the right lower quadrant of the abdomen 3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented allergy to any of the study medications, acute or renal insufficiency at&#xD;
             admission, and severe septic shock at admission.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pediatric Surgery Department, HaEmek Medical Center</name>
      <address>
        <city>Afula</city>
        <zip>18101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>July 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <last_update_submitted>September 3, 2012</last_update_submitted>
  <last_update_submitted_qc>September 3, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 5, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>HaEmek Medical Center, Israel</investigator_affiliation>
    <investigator_full_name>Dan Miron, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>complicated appendicitis</keyword>
  <keyword>Children</keyword>
  <keyword>conservative therapy</keyword>
  <keyword>Study population: Children 1 month - 14 years with Complicated appendicitis</keyword>
  <keyword>Type of the study: prospective, open randomized</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Appendicitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metronidazole</mesh_term>
    <mesh_term>Gentamicins</mesh_term>
    <mesh_term>Ceftriaxone</mesh_term>
    <mesh_term>Ampicillin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01678365
org study id: 043-07-EMC
nct id: NCT01678365
lead sponsor: 
has dmc: Yes
A prospective open randomized study conducted between July 1st 2008 and June 30th, 2009.
      Included were children younger than 14 years with Complicated appendicitis randomly assigned
      either to a single daily dose of Ceftriaxone and Metronidazole or Ampicillin, Gentamicin, and
      Metronidazole. The outcome variables compared were: maximum daily temperatures, overall
      duration of fever, time return to oral intake, length of antibiotic therapy, results of
      repeat WBC measure, general/intra abdominal complications, need for intra abdominal abscess
      drainage, Length of stay and adverse reaction.
The study was conducted at the Pediatric Surgery Department at HaEmek Medical Center, Afula,
      Israel. Included were children age 1-14 years with complicated appendicitis that was defined
      by one of the followings: 1. Demonstration by abdominal ultrasound and/or computed tomography
      of appendix perforation and/or peri-appendicular abscess 2. Demonstration by abdominal
      ultrasound of free fluid, and signs of diffuse peritoneal irritation in the right lower
      quadrant of the abdomen 3. At surgery performed for suspected non complicated appendicitis.
      In a patient with perforate appendicitis that was diagnosed at surgery, appendectomy was
      performed by one of the 4 senior pediatric surgeons on call at the time of the child's
      admission. Exclusion criteria were: documented allergy to any of the study medications, acute
      or renal insufficiency at admission, and severe septic shock at admission.

      Therapeutic approach: After the diagnosis of complicated appendicitis was established,
      patients were randomly assigned to therapy with either once daily of ceftriaxone and
      metronidazole or ampicillin, gentamicin and metronidazole. Therapy was change to
      piperacillin/tazobactam in patients who were still febrile at day 7-10 of the admission (if
      not given before), based on the clinical situation, and in all febrile patients at 11 day of
      the admission . All patients had also been treats after inclusion with pain control
      medications, no oral food or fluid , and intravenous hydration as necessary. Nasogastric
      tubes were not used routinely. On the fifth admission day patients who were stable, a
      febrile, could tolerate diet and had Complete blood count within normal limits were
      discharged home with oral amoxicillin/clavulanate therapy for further 7 days.

      Follow-up at the admission: CBC and renal and liver function tests were obtained before
      starting the antibiotic treatment and repeated on day 4 in all patients. In the group treated
      with AGM, serum trough gentamicin concentration was drawn before the fourth dose with normal
      level considered as < 2 mcg/ml. Other blood studies were performed based on the discretion of
      the attending physician based on the patient's clinical status. For patients who were either
      febrile or had leukocytosis, at day 5 of therapy abdominal ultrasound was obtained to assess
      for the presence of an abscess. Patients in whom abscesses were delectated undergone per
      coetaneous drainage (when possible). The original antibiotic regimen was either continued or
      changed to piperacillin/tazobactam based on the clinical situation. Patients, in whom
      appendectomy had not been done at admission, were readmitted for appendectomy at 6 weeks. All
      patients had been followed for a year since the admission for signs of intra abdominal
      complication such: repeat abscess formation, repeat admission, obstruction etc.

      Data collection: Data were recorded were: patient's age, weight, gender, maximum daily
      temperature, duration of fever, results of complete blood count, renal and liver function
      tests, gentamicin levels (where applicable), intra abdominal complications and duration of
      hospitalization. The outcome variables included maximum daily temperatures for each of the
      first 10 postoperative days, time to initial oral intake, length of hospitalization, length
      of antibiotic therapy, abscess formation rate, need to change antibiotic regimen, wound
      infection rate, and any abnormal findings during the follow-up visits.

      Statistical analysis: Since data in the literature show that there is no difference of the
      length of stay in between the 2 regimens (in children with complicated appendicitis following
      operation), and most studies included relatively low number of patients, no power analysis
      was calculated. The difference between various parameters in the two treatment groups were
      assessed by 2 independent sample T tests or Fisher exact tests for categorical data and 2
      independent sample t test or the Mann Whitney test for continuous data. Descriptive
      statistics were calculated as mean ± SD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Length of stay (days)
time frame: From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks
measure: Change of primary antibiotic regimen to Piperacillin/tazobactam
time frame: From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks
measure: Number of new intrabdominal abcesses
time frame: From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks
measure: Re hospitalization due to intra abdominal abcess formation
time frame: Within 2 years after day of discharge
arm group label: ceftriaxone and metronidazole for complicated appendicitis.
arm group type: Experimental
description: Children with complicated appendicitis treated with single daily dose of ceftriaxone and metronidazole.
arm group label: Ampicillin, gentamicin, and metronidazole
arm group type: Active Comparator
description: Children with complicated appendicitis treated with ampicillin, gentamicin, and metronidazole
intervention type: Drug
intervention name: ceftriaxone, metronidazole/ampicillin, gentamicin, and metronidazole
arm group label: Ampicillin, gentamicin, and metronidazole
arm group label: ceftriaxone and metronidazole for complicated appendicitis.
criteria: 
gender: All
minimum age: 1 Year
maximum age: 14 Years
healthy volunteers: No
facility: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: HaEmek Medical Center, Israel
investigator full name: Dan Miron, MD
investigator title: Professor
mesh term: Appendicitis
mesh term: Metronidazole
mesh term: Gentamicins
mesh term: Ceftriaxone
mesh term: Ampicillin