<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/NCT01697059</url>
  </required_header>
  <id_info>
    <org_study_id>RIH408212</org_study_id>
    <nct_id>NCT01697059</nct_id>
  </id_info>
  <brief_title>Initial Antibiotics and Delayed Appendectomy for Acute Appendicitis</brief_title>
  <official_title>Initial Antibiotics and Delayed Appendectomy for Acute Appendicitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rhode Island Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Several recent studies have examined the feasibility and benefits of nonoperative treatment&#xD;
      of perforated appendicitis in children. One such study showed a trend toward longer operative&#xD;
      times for patients randomized to immediate appendectomy, but no overall advantage. In another&#xD;
      larger study, the costs of delayed appendectomy for perforated appendicitis were higher - in&#xD;
      part related to readmissions in the interval (6-8 weeks). Nevertheless, these and other&#xD;
      studies have demonstrated the safety of delaying appendectomy for perforated appendicitis.&#xD;
&#xD;
      Emergency appendectomy is a well-established approach, and postoperative recovery in children&#xD;
      is fast. Nevertheless, from the onset of symptoms through the hospital stay and the&#xD;
      postoperative recovery, appendicitis causes a disruption of a family's normal routine&#xD;
      (absence from school and work) of up to 1-2 weeks. Because this is an unplanned operation,&#xD;
      patients have to wait until an operating room becomes available, or elective operations have&#xD;
      to be placed on hold to accommodate the emergency operation. Each year, more than 250&#xD;
      children undergo an appendectomy at HCH. This represents 250 episodes of emergency surgery,&#xD;
      or about one emergency add-on operation per working day. If an initial trial of antibiotics&#xD;
      is safe for the treatment of appendicitis, converting an emergency operation into an&#xD;
      elective, scheduled outpatient procedure may reduce stress and disruption of routine for&#xD;
      patients and their families - and may allow better operating room planning for health care&#xD;
      professionals and hospitals.&#xD;
&#xD;
      The investigators hypothesize that initial antibiotic treatment of acute (non-perforated)&#xD;
      appendicitis, followed by scheduled outpatient appendectomy, reduces the overall cost of&#xD;
      treating the disease and results in greater patient and family satisfaction.&#xD;
&#xD;
      This pilot study aims to establish the safety and feasibility of treating acute appendicitis&#xD;
      with intravenous antibiotics, followed by outpatient oral antibiotics. Patients and their&#xD;
      families will be offered the possibility of initial nonoperative treatment and subsequent&#xD;
      outpatient elective appendectomy in a nonrandomized, single arm study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of treatment failures</measure>
    <time_frame>Worsening of symptoms at 8 hours or failure of improvement at 18 hours of treatment</time_frame>
    <description>If after a period of at least 8 hours (and 2 doses of intravenous antibiotics), the patient's symptoms worsen, or fail to subside within 18 hours, the patient will undergo an emergent/urgent appendectomy, and treatment will proceed as per standard-of-care (1 intraoperative dose of antibiotics, with or without postoperative antibiotics, progressive postoperative diet and discharge home once tolerating a regular diet). The patient will then be considered having failed nonoperative treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cost-saving of initial nonoperative treatment for early appendicitis</measure>
    <time_frame>1 year</time_frame>
    <description>Cost of nonoperative treatment will be calculated as follows: Hospitalization charges (# hospital days - observation) + costs of antibiotics (actual number of doses/days) + outpatient surgery hospital fee (operating room and PACU time) + additional costs associated with unanticipated events (e.g., Emergency room visits after initial discharge).&#xD;
Control costs (contemporary data) will consider the following: Hospitalization charges (# hospital days) + intravenous antibiotics (price/dose x number of doses).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Utility of initial nonoperative treatment of early appendicitis</measure>
    <time_frame>1 year</time_frame>
    <description>Questionnaires given to parents and patients regarding their experience of initial nonoperative treatment and interval appendectomy will be analyzed, and compared with controls and with standard levels in the literature.&#xD;
The Pediatric Quality of Life Scale-Version 4.0 (PedsQL) is a reliable and valid 23-item questionnaire that measures child health-related quality of life (QOL) in the preceding month. Items can be recoded from 100 to 0 on 25-point intervals and averaged to produce a total score (α=0.90). The total score is derived from items that assess the child's physical (e.g., problems with low energy or difficulty lifting something heavy), emotional (e.g., feeling afraid, angry, or scared), social (e.g., problems with getting teased or other children not wanting to be friends), and school functioning (e.g., problems paying attention in class or missing school). Higher scores indicate better QOL.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Acute Appendicitis</condition>
  <arm_group>
    <arm_group_label>Piperacillin + Amoxicillin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Piperacillin/Tazobactam (Zosyn®) 100 mg/kg, up to adult dose of 3 g, i.v. q 6 hours x 2 doses, followed by Ampicillin/Clavulanate (Augmentin®) 50 mg/kg/d p.o. in 3 divided doses for 1 week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Piperacillin + Amoxicillin</intervention_name>
    <arm_group_label>Piperacillin + Amoxicillin</arm_group_label>
    <other_name>Zosyn®</other_name>
    <other_name>Augmentin®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Maximum 48-hour-history of abdominal pain&#xD;
&#xD;
          -  Diagnosis of acute appendicitis based on clinical, laboratory and/or radiologic&#xD;
             criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Duration of symptoms &gt; 48 hours&#xD;
&#xD;
          -  Presence of an appendiceal abscess on imaging&#xD;
&#xD;
          -  Clinical or laboratory suspicion of advanced appendicitis, peritonitis or perforation&#xD;
&#xD;
          -  Significant comorbidities&#xD;
&#xD;
          -  Inability or unwillingness to complete a 1-week course of oral antibiotics&#xD;
&#xD;
          -  Allergy to penicillin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francois I. Luks, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rhode Island Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hasbro Children's Hospital (Rhode Island Hospital)</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Narsule CK, Kahle EJ, Kim DS, Anderson AC, Luks FI. Effect of delay in presentation on rate of perforation in children with appendicitis. Am J Emerg Med. 2011 Oct;29(8):890-3. doi: 10.1016/j.ajem.2010.04.005. Epub 2010 Jul 13.</citation>
    <PMID>20627213</PMID>
  </reference>
  <reference>
    <citation>Powers RJ, Andrassy RJ, Brennan LP, Weitzman JJ. Alternate approach to the management of acute perforating appendicitis in children. Surg Gynecol Obstet. 1981 Apr;152(4):473-5.</citation>
    <PMID>7209777</PMID>
  </reference>
  <reference>
    <citation>St Peter SD, Aguayo P, Fraser JD, Keckler SJ, Sharp SW, Leys CM, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Holcomb GW 3rd, Ostlie DJ. Initial laparoscopic appendectomy versus initial nonoperative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial. J Pediatr Surg. 2010 Jan;45(1):236-40. doi: 10.1016/j.jpedsurg.2009.10.039.</citation>
    <PMID>20105610</PMID>
  </reference>
  <reference>
    <citation>Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, Rex L, Badume I, Granstrom L. Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial. World J Surg. 2006 Jun;30(6):1033-7. doi: 10.1007/s00268-005-0304-6.</citation>
    <PMID>16736333</PMID>
  </reference>
  <reference>
    <citation>Yardeni D, Hirschl RB, Drongowski RA, Teitelbaum DH, Geiger JD, Coran AG. Delayed versus immediate surgery in acute appendicitis: do we need to operate during the night? J Pediatr Surg. 2004 Mar;39(3):464-9; discussion 464-9. doi: 10.1016/j.jpedsurg.2003.11.020.</citation>
    <PMID>15017571</PMID>
  </reference>
  <verification_date>May 2015</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>May 4, 2015</last_update_submitted>
  <last_update_submitted_qc>May 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 6, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rhode Island Hospital</investigator_affiliation>
    <investigator_full_name>Francois Luks</investigator_full_name>
    <investigator_title>Francois I. Luks, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>appendicitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Appendicitis</mesh_term>
    <mesh_term>Acute Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Piperacillin</mesh_term>
    <mesh_term>Amoxicillin-Potassium Clavulanate Combination</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/NCT01697059
org study id: RIH408212
nct id: NCT01697059
lead sponsor: 
has dmc: No
Several recent studies have examined the feasibility and benefits of nonoperative treatment
      of perforated appendicitis in children. One such study showed a trend toward longer operative
      times for patients randomized to immediate appendectomy, but no overall advantage. In another
      larger study, the costs of delayed appendectomy for perforated appendicitis were higher - in
      part related to readmissions in the interval (6-8 weeks). Nevertheless, these and other
      studies have demonstrated the safety of delaying appendectomy for perforated appendicitis.

      Emergency appendectomy is a well-established approach, and postoperative recovery in children
      is fast. Nevertheless, from the onset of symptoms through the hospital stay and the
      postoperative recovery, appendicitis causes a disruption of a family's normal routine
      (absence from school and work) of up to 1-2 weeks. Because this is an unplanned operation,
      patients have to wait until an operating room becomes available, or elective operations have
      to be placed on hold to accommodate the emergency operation. Each year, more than 250
      children undergo an appendectomy at HCH. This represents 250 episodes of emergency surgery,
      or about one emergency add-on operation per working day. If an initial trial of antibiotics
      is safe for the treatment of appendicitis, converting an emergency operation into an
      elective, scheduled outpatient procedure may reduce stress and disruption of routine for
      patients and their families - and may allow better operating room planning for health care
      professionals and hospitals.

      The investigators hypothesize that initial antibiotic treatment of acute (non-perforated)
      appendicitis, followed by scheduled outpatient appendectomy, reduces the overall cost of
      treating the disease and results in greater patient and family satisfaction.

      This pilot study aims to establish the safety and feasibility of treating acute appendicitis
      with intravenous antibiotics, followed by outpatient oral antibiotics. Patients and their
      families will be offered the possibility of initial nonoperative treatment and subsequent
      outpatient elective appendectomy in a nonrandomized, single arm study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of treatment failures
time frame: Worsening of symptoms at 8 hours or failure of improvement at 18 hours of treatment
description: If after a period of at least 8 hours (and 2 doses of intravenous antibiotics), the patient's symptoms worsen, or fail to subside within 18 hours, the patient will undergo an emergent/urgent appendectomy, and treatment will proceed as per standard-of-care (1 intraoperative dose of antibiotics, with or without postoperative antibiotics, progressive postoperative diet and discharge home once tolerating a regular diet). The patient will then be considered having failed nonoperative treatment.
measure: Cost-saving of initial nonoperative treatment for early appendicitis
time frame: 1 year
description: Cost of nonoperative treatment will be calculated as follows: Hospitalization charges (# hospital days - observation) + costs of antibiotics (actual number of doses/days) + outpatient surgery hospital fee (operating room and PACU time) + additional costs associated with unanticipated events (e.g., Emergency room visits after initial discharge).
Control costs (contemporary data) will consider the following: Hospitalization charges (# hospital days) + intravenous antibiotics (price/dose x number of doses).
measure: Utility of initial nonoperative treatment of early appendicitis
time frame: 1 year
description: Questionnaires given to parents and patients regarding their experience of initial nonoperative treatment and interval appendectomy will be analyzed, and compared with controls and with standard levels in the literature.
The Pediatric Quality of Life Scale-Version 4.0 (PedsQL) is a reliable and valid 23-item questionnaire that measures child health-related quality of life (QOL) in the preceding month. Items can be recoded from 100 to 0 on 25-point intervals and averaged to produce a total score (α=0.90). The total score is derived from items that assess the child's physical (e.g., problems with low energy or difficulty lifting something heavy), emotional (e.g., feeling afraid, angry, or scared), social (e.g., problems with getting teased or other children not wanting to be friends), and school functioning (e.g., problems paying attention in class or missing school). Higher scores indicate better QOL.
arm group label: Piperacillin + Amoxicillin
arm group type: Experimental
description: Piperacillin/Tazobactam (Zosyn®) 100 mg/kg, up to adult dose of 3 g, i.v. q 6 hours x 2 doses, followed by Ampicillin/Clavulanate (Augmentin®) 50 mg/kg/d p.o. in 3 divided doses for 1 week.
intervention type: Drug
intervention name: Piperacillin + Amoxicillin
arm group label: Piperacillin + Amoxicillin
other name: Zosyn®
other name: Augmentin®
criteria: 
gender: All
minimum age: 5 Years
maximum age: 18 Years
healthy volunteers: No
last name: Francois I. Luks, MD, PhD
role: Principal Investigator
affiliation: Rhode Island Hospital
facility: 
country: United States
citation: Narsule CK, Kahle EJ, Kim DS, Anderson AC, Luks FI. Effect of delay in presentation on rate of perforation in children with appendicitis. Am J Emerg Med. 2011 Oct;29(8):890-3. doi: 10.1016/j.ajem.2010.04.005. Epub 2010 Jul 13.
PMID: 20627213
citation: Powers RJ, Andrassy RJ, Brennan LP, Weitzman JJ. Alternate approach to the management of acute perforating appendicitis in children. Surg Gynecol Obstet. 1981 Apr;152(4):473-5.
PMID: 7209777
citation: St Peter SD, Aguayo P, Fraser JD, Keckler SJ, Sharp SW, Leys CM, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Holcomb GW 3rd, Ostlie DJ. Initial laparoscopic appendectomy versus initial nonoperative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial. J Pediatr Surg. 2010 Jan;45(1):236-40. doi: 10.1016/j.jpedsurg.2009.10.039.
PMID: 20105610
citation: Styrud J, Eriksson S, Nilsson I, Ahlberg G, Haapaniemi S, Neovius G, Rex L, Badume I, Granstrom L. Appendectomy versus antibiotic treatment in acute appendicitis. a prospective multicenter randomized controlled trial. World J Surg. 2006 Jun;30(6):1033-7. doi: 10.1007/s00268-005-0304-6.
PMID: 16736333
citation: Yardeni D, Hirschl RB, Drongowski RA, Teitelbaum DH, Geiger JD, Coran AG. Delayed versus immediate surgery in acute appendicitis: do we need to operate during the night? J Pediatr Surg. 2004 Mar;39(3):464-9; discussion 464-9. doi: 10.1016/j.jpedsurg.2003.11.020.
PMID: 15017571
responsible party type: Principal Investigator
investigator affiliation: Rhode Island Hospital
investigator full name: Francois Luks
investigator title: Francois I. Luks, MD, PhD
mesh term: Appendicitis
mesh term: Acute Disease
mesh term: Amoxicillin
mesh term: Piperacillin
mesh term: Amoxicillin-Potassium Clavulanate Combination