<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/NCT03236961</url>
  </required_header>
  <id_info>
    <org_study_id>APPAC II</org_study_id>
    <nct_id>NCT03236961</nct_id>
  </id_info>
  <brief_title>Optimizing the Antibiotic Treatment of Uncomplicated Acute Appendicitis</brief_title>
  <acronym>APPACII</acronym>
  <official_title>Optimizing the Antibiotic Treatment of Uncomplicated Acute Appendicitis: a Prospective Randomised Multicenter Study (The APPAC II Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Turku University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oulu University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tampere University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kuopio University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mikkeli Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lapland Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jyväskylä Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Satakunta Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seinajoki Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Turku University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Appendicectomy has been the treatment of acute appendicitis for over a hundred years.&#xD;
      Appendicectomy, however, includes operative and postoperative risks despite being a routine&#xD;
      procedure. Several studies have proved promising results of the safety and efficiency of&#xD;
      antibiotics in the treatment of acute uncomplicated appendicitis. The APPAC study by the&#xD;
      investigators, published in 2015 in the Journal of American Medical Association, also proved&#xD;
      promising results with 73% of patients with uncomplicated appendicitis treated successfully&#xD;
      with antibiotics. None of the patients initially treated with antibiotics that later had&#xD;
      appendectomy had major complications. The results of the APPAC trial suggest that CT proven&#xD;
      uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe&#xD;
      first-line treatment option. Reducing unnecessary appendectomies has also been shown to lead&#xD;
      to significant economic savings.&#xD;
&#xD;
      The aim of this randomized prospective study is to optimize antibiotic therapy for&#xD;
      uncomplicated acute appendicitis by comparing different antibiotic regimens; intravenous&#xD;
      antibiotic (ertapenem) followed by per oral antibiotic (levofloxacin and metronidazole) with&#xD;
      only per oral antibiotics (moxifloxacin). Before randomization, the diagnosis of acute&#xD;
      uncomplicated appendicitis is confirmed with a CT scan.&#xD;
&#xD;
      The hypothesis is that broad-spectrum intravenous antibiotics requiring additional hospital&#xD;
      resources are not necessary for the treatment of uncomplicated acute appendicitis and that&#xD;
      per oral mono therapy is non-inferior to the combination of intravenous and per oral&#xD;
      antibiotic therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute appendicitis is the most common cause of abdominal pain in emergency departments and&#xD;
      appendectomy is the most common emergency abdominal surgery. The lifetime risk of acute&#xD;
      appendicitis in males is 8.6% and 6.7% in females. In Finland according to Stakes data there&#xD;
      were 6 377 appendectomies (3242 in males, 3135 in females, median age 35 years) performed in&#xD;
      2010. The total number of days in hospital care was 16 111 days and the mean length of&#xD;
      hospital stay was three days.&#xD;
&#xD;
      Although acute appendicitis is the most common reason for surgical emergency department&#xD;
      visit, its diagnosis still remains challenging. The clinical diagnosis has previously been&#xD;
      based on patient history, physical examination and laboratory findings as well as the&#xD;
      clinical surgical diagnosis. Several scoring systems have been created to aid in the&#xD;
      diagnosis of acute appendicitis18-20, but the accuracy of clinical diagnosis without&#xD;
      preoperative imaging is about 76 - 80 % for combined patient groups of males and females.&#xD;
&#xD;
      As acute appendicitis has historically been thought to always progress to perforation&#xD;
      requiring emergency appendectomy, high negative appendectomy rates even up to 40 % in some&#xD;
      patient populations have been previously accepted as good surgical practice. For the last two&#xD;
      decades, the use of dedicated imaging in acute abdomen in general and also in acute&#xD;
      appendicitis has led to improved diagnostic accuracy.&#xD;
&#xD;
      Based on large epidemiological studies, it is now known that complicated (perforated) and&#xD;
      uncomplicated (non-perforated) appendicitis have followed different epidemiological trends.&#xD;
      These unassociated epidemiologic trends suggest different pathophysiology for the two form of&#xD;
      appendicitis. The differential diagnosis is essential as patients with an uncomplicated acute&#xD;
      appendicitis may not require surgical intervention and might experience even spontaneous&#xD;
      resolution without perforation. The majority (approximately 80 %) of acute appendicitis cases&#xD;
      are of uncomplicated nature.&#xD;
&#xD;
      Complicated acute appendicitis defined as a finding of a perforation, appendicolith, abscess&#xD;
      or a suspicion of a tumor, requires emergency appendectomy with the exception of cases with&#xD;
      abscess as they are often managed conservatively.&#xD;
&#xD;
      Appendicolith is a calcified fecal concretion in the appendix resulting in internal luminal&#xD;
      obstruction and it is the most common form of complicated acute appendicitis. In the first&#xD;
      randomized study by Vons et al. comparing operative treatment and antibiotic therapy using CT&#xD;
      as a diagnostic inclusion criterion, the presence of an appendicolith in preoperative CT scan&#xD;
      was the only factor that significantly increased the risk of complicated appendicitis and it&#xD;
      was also the only factor associated with the failure of antibiotic therapy for acute&#xD;
      appendicitis. Indeed, if Vons et al had excluded the patients with an appendicolith from&#xD;
      their analysis, no significant difference in the incidence of post-intervention peritonitis&#xD;
      between the treatment groups would have been noticed in their study.&#xD;
&#xD;
      CT imaging is the primary imaging modality and the golden standard in the diagnosis of acute&#xD;
      appendicitis as it establishes the diagnosis with almost perfect diagnostic accuracy. The&#xD;
      advantages of CT imaging are high accuracy, availability, ease of performance and&#xD;
      interpretation, and that it is rarely affected by bowel gas, severe abdominal pain or extreme&#xD;
      body habitus. The main disadvantage of CT is exposure to radiation.&#xD;
&#xD;
      The increased use of preoperative CT imaging has been evaluated thoroughly by evaluating its&#xD;
      impact on the negative appendectomy rate reducing the number of unnecessary appendectomies.&#xD;
      In 2010, a mandatory imaging guideline for suspected acute appendicitis was implemented in&#xD;
      the Netherlands. After implementation the negative appendectomy rate dropped significantly&#xD;
      from 23 % to 6 % (p&lt;0.001) reducing the surgical complication rate from 20% to 14 % and&#xD;
      resulting in average cost-per-patient decrease by 594€.&#xD;
&#xD;
      The favorable diagnostic performance of CT imaging has encouraged optimization of the&#xD;
      protocol to minimize exposure to radiation through the development of low-dose CT protocols.&#xD;
      Low-dose protocols balance with as low as reasonably achievable-principle while maintaining&#xD;
      diagnostic accuracy. However, low-dose protocols with intravenous contrast are still not&#xD;
      implemented in routine clinical practice. These protocols require more advanced optimization&#xD;
      and validation because of the wider need for contrast enhanced assessment. Kim et al showed&#xD;
      that contrast enhanced low-dose CT (median radiation dose 116mmGy in dose-length product) was&#xD;
      not inferior to standard-dose contrast enhanced CT (median radiation dose 521 mmGy), with&#xD;
      negative appendectomy rates of 3.5% and 3.2% respectively and no statistical significance in&#xD;
      appendiceal perforation rates or patients requiring additional imaging.&#xD;
&#xD;
      The investigators have performed a prospective observational study (OPTICAP trial,&#xD;
      NCT02533869, Ethical committee of Turku University Hospital approval) in order to optimize a&#xD;
      low-dose CT scan for both diagnosing acute appendicitis and to differentiate uncomplicated&#xD;
      acute appendicitis from a complicated acute appendicitis. In this study, phantom imaging with&#xD;
      15 different imaging protocols were performed aiming to minimize radiation with optimal&#xD;
      diagnostic accuracy. The phantom protocols were assessed by blinded evaluation of two&#xD;
      gastrointestinal radiologists and the two best performing protocols were chosen for the&#xD;
      clinical phase. The clinical evaluation included performing both of these imaging protocols&#xD;
      for patients with suspected uncomplicated acute appendicitis evaluated by a senior digestive&#xD;
      surgeon. All of the enrolled patients underwent laparoscopic appendectomy to evaluate the&#xD;
      sensitivity and specificity of the imaging protocols. The most optimal imaging protocols were&#xD;
      selected for use in the APPAC II trial; one low-dose CT protocol for patients with BMI under&#xD;
      30 and one optimised standard CT protocol for patients with BMI exceeding 30.&#xD;
&#xD;
      For over a century appendectomy has been the standard treatment for all patients with acute&#xD;
      appendicitis. However, the results of our APPAC trial have now shown that the majority (73%)&#xD;
      of patients with uncomplicated acute appendicitis were successfully treated with antibiotics&#xD;
      alone. We also showed that none of the patients treated initially with antibiotics and later&#xD;
      undergoing appendectomy had major complications or increased morbidity defining antibiotic&#xD;
      therapy as a safe first-line treatment. Patients with a complicated acute appendicitis&#xD;
      require emergency appendectomy and early identification of these patients is of vital&#xD;
      importance. Laparoscopic appendectomy has become the golden standard for appendectomy&#xD;
      providing lower morbidity and faster recovery compared with open appendectomy. For patients&#xD;
      with uncomplicated acute appendicitis, the time has come to evaluate abandoning routine&#xD;
      appendectomy and evaluating the optimal use of antibiotic therapy.&#xD;
&#xD;
      The aim of study is to optimize the antibiotic therapy for uncomplicated acute appendicitis&#xD;
      by evaluating the success of treatment in both study groups and by comparing intravenous&#xD;
      antibiotic therapy followed by per oral antibiotics with per oral antibiotic monotherapy. The&#xD;
      study hypothesis is that broad-spectrum intravenous antibiotics requiring additional hospital&#xD;
      resources are not necessary for the treatment of uncomplicated acute appendicitis and that&#xD;
      per oral monotherapy is non-inferior to the combination of intravenous and per oral&#xD;
      antibiotic therapy. The secondary aim is to evaluate the results of the randomized APPAC&#xD;
      trial in a prospective patient cohort by implementing antibiotic therapy as the first-line&#xD;
      treatment for uncomplicated acute appendicitis in clinical practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 3, 2017</start_date>
  <completion_date type="Anticipated">April 1, 2029</completion_date>
  <primary_completion_date type="Actual">November 27, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open-label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment success</measure>
    <time_frame>1 year</time_frame>
    <description>The resolution of acute uncomplicated appendicitis with allocated antibiotic treatment. Treatment success is defined as discharge from the hospital without the need for surgical intervention after the primary hospitalisation and no recurrent appendicitis during one-year follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Late recurrence of appendicitis after antibiotic treatment</measure>
    <time_frame>1 year</time_frame>
    <description>Recurring appendicitis after primary treatment considered successful, thus recurrence after one year</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>1 month</time_frame>
    <description>Hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-intervention complications</measure>
    <time_frame>10 years</time_frame>
    <description>Complications according to the Clavien-Dindo classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VAS pain score (visual analogue score)</measure>
    <time_frame>10 years</time_frame>
    <description>Pain as described with a scale from 0-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sick leave</measure>
    <time_frame>1 month</time_frame>
    <description>Duration of sick leave</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment costs</measure>
    <time_frame>1 year</time_frame>
    <description>Treatment costs including hospital stay costs, medicinal costs, imaging costs, costs to treat possible complications, operative costs</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">552</enrollment>
  <condition>Acute Appendicitis</condition>
  <arm_group>
    <arm_group_label>Intravenous &amp; per oral antibiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ertapenem 1 g x 1 for two days i.v. followed by p.o. levofloxacin 500 mg x 1 and metronidazole 500 mg x 3 for 5 days, duration of treatment one week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Per oral antibiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Moxifloxacin 400 mg x 1 foe seven days, duration of treatment one week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ertapenem</intervention_name>
    <description>I.v. ertapenem 1 g for 2 days followed by p.o. levofloxacin 500 mg x1 and metronidazole 500 mg x 3 for 5 days</description>
    <arm_group_label>Intravenous &amp; per oral antibiotics</arm_group_label>
    <other_name>Levofloxacin</other_name>
    <other_name>Metronidazole</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <description>P.o. moxifloxacin 400 mg x1 for 7 days</description>
    <arm_group_label>Per oral antibiotics</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-60 years&#xD;
&#xD;
          -  CT confirmed uncomplicated acute appendicitis&#xD;
&#xD;
          -  Ability to give consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age under 18 years or over 60 years&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Allergy to contrast media or iodine&#xD;
&#xD;
          -  Allergy or contraindication to antibiotic therapy&#xD;
&#xD;
          -  Renal insufficiency&#xD;
&#xD;
          -  Metformin medication&#xD;
&#xD;
          -  Severe systemic illness (for example malignancy, medical condition requiring&#xD;
             immunosuppressant medication)&#xD;
&#xD;
          -  CT confirmed complicated acute appendicitis&#xD;
&#xD;
          -  Inability to co-operate and give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paulina Salminen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Turku University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Turku University Hospital</name>
      <address>
        <city>Turku</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>November 10, 2020</last_update_submitted>
  <last_update_submitted_qc>November 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Turku University Hospital</investigator_affiliation>
    <investigator_full_name>Paulina Salminen</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>uncomplicated acute appendicitis</keyword>
  <keyword>complicated acute appendicitis</keyword>
  <keyword>antibiotic therapy</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>Moxifloxacin</mesh_term>
    <mesh_term>Metronidazole</mesh_term>
    <mesh_term>Levofloxacin</mesh_term>
    <mesh_term>Ertapenem</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03236961
org study id: APPAC II
nct id: NCT03236961
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Appendicectomy has been the treatment of acute appendicitis for over a hundred years.
      Appendicectomy, however, includes operative and postoperative risks despite being a routine
      procedure. Several studies have proved promising results of the safety and efficiency of
      antibiotics in the treatment of acute uncomplicated appendicitis. The APPAC study by the
      investigators, published in 2015 in the Journal of American Medical Association, also proved
      promising results with 73% of patients with uncomplicated appendicitis treated successfully
      with antibiotics. None of the patients initially treated with antibiotics that later had
      appendectomy had major complications. The results of the APPAC trial suggest that CT proven
      uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe
      first-line treatment option. Reducing unnecessary appendectomies has also been shown to lead
      to significant economic savings.

      The aim of this randomized prospective study is to optimize antibiotic therapy for
      uncomplicated acute appendicitis by comparing different antibiotic regimens; intravenous
      antibiotic (ertapenem) followed by per oral antibiotic (levofloxacin and metronidazole) with
      only per oral antibiotics (moxifloxacin). Before randomization, the diagnosis of acute
      uncomplicated appendicitis is confirmed with a CT scan.

      The hypothesis is that broad-spectrum intravenous antibiotics requiring additional hospital
      resources are not necessary for the treatment of uncomplicated acute appendicitis and that
      per oral mono therapy is non-inferior to the combination of intravenous and per oral
      antibiotic therapy.
Acute appendicitis is the most common cause of abdominal pain in emergency departments and
      appendectomy is the most common emergency abdominal surgery. The lifetime risk of acute
      appendicitis in males is 8.6% and 6.7% in females. In Finland according to Stakes data there
      were 6 377 appendectomies (3242 in males, 3135 in females, median age 35 years) performed in
      2010. The total number of days in hospital care was 16 111 days and the mean length of
      hospital stay was three days.

      Although acute appendicitis is the most common reason for surgical emergency department
      visit, its diagnosis still remains challenging. The clinical diagnosis has previously been
      based on patient history, physical examination and laboratory findings as well as the
      clinical surgical diagnosis. Several scoring systems have been created to aid in the
      diagnosis of acute appendicitis18-20, but the accuracy of clinical diagnosis without
      preoperative imaging is about 76 - 80 % for combined patient groups of males and females.

      As acute appendicitis has historically been thought to always progress to perforation
      requiring emergency appendectomy, high negative appendectomy rates even up to 40 % in some
      patient populations have been previously accepted as good surgical practice. For the last two
      decades, the use of dedicated imaging in acute abdomen in general and also in acute
      appendicitis has led to improved diagnostic accuracy.

      Based on large epidemiological studies, it is now known that complicated (perforated) and
      uncomplicated (non-perforated) appendicitis have followed different epidemiological trends.
      These unassociated epidemiologic trends suggest different pathophysiology for the two form of
      appendicitis. The differential diagnosis is essential as patients with an uncomplicated acute
      appendicitis may not require surgical intervention and might experience even spontaneous
      resolution without perforation. The majority (approximately 80 %) of acute appendicitis cases
      are of uncomplicated nature.

      Complicated acute appendicitis defined as a finding of a perforation, appendicolith, abscess
      or a suspicion of a tumor, requires emergency appendectomy with the exception of cases with
      abscess as they are often managed conservatively.

      Appendicolith is a calcified fecal concretion in the appendix resulting in internal luminal
      obstruction and it is the most common form of complicated acute appendicitis. In the first
      randomized study by Vons et al. comparing operative treatment and antibiotic therapy using CT
      as a diagnostic inclusion criterion, the presence of an appendicolith in preoperative CT scan
      was the only factor that significantly increased the risk of complicated appendicitis and it
      was also the only factor associated with the failure of antibiotic therapy for acute
      appendicitis. Indeed, if Vons et al had excluded the patients with an appendicolith from
      their analysis, no significant difference in the incidence of post-intervention peritonitis
      between the treatment groups would have been noticed in their study.

      CT imaging is the primary imaging modality and the golden standard in the diagnosis of acute
      appendicitis as it establishes the diagnosis with almost perfect diagnostic accuracy. The
      advantages of CT imaging are high accuracy, availability, ease of performance and
      interpretation, and that it is rarely affected by bowel gas, severe abdominal pain or extreme
      body habitus. The main disadvantage of CT is exposure to radiation.

      The increased use of preoperative CT imaging has been evaluated thoroughly by evaluating its
      impact on the negative appendectomy rate reducing the number of unnecessary appendectomies.
      In 2010, a mandatory imaging guideline for suspected acute appendicitis was implemented in
      the Netherlands. After implementation the negative appendectomy rate dropped significantly
      from 23 % to 6 % (p<0.001) reducing the surgical complication rate from 20% to 14 % and
      resulting in average cost-per-patient decrease by 594€.

      The favorable diagnostic performance of CT imaging has encouraged optimization of the
      protocol to minimize exposure to radiation through the development of low-dose CT protocols.
      Low-dose protocols balance with as low as reasonably achievable-principle while maintaining
      diagnostic accuracy. However, low-dose protocols with intravenous contrast are still not
      implemented in routine clinical practice. These protocols require more advanced optimization
      and validation because of the wider need for contrast enhanced assessment. Kim et al showed
      that contrast enhanced low-dose CT (median radiation dose 116mmGy in dose-length product) was
      not inferior to standard-dose contrast enhanced CT (median radiation dose 521 mmGy), with
      negative appendectomy rates of 3.5% and 3.2% respectively and no statistical significance in
      appendiceal perforation rates or patients requiring additional imaging.

      The investigators have performed a prospective observational study (OPTICAP trial,
      NCT02533869, Ethical committee of Turku University Hospital approval) in order to optimize a
      low-dose CT scan for both diagnosing acute appendicitis and to differentiate uncomplicated
      acute appendicitis from a complicated acute appendicitis. In this study, phantom imaging with
      15 different imaging protocols were performed aiming to minimize radiation with optimal
      diagnostic accuracy. The phantom protocols were assessed by blinded evaluation of two
      gastrointestinal radiologists and the two best performing protocols were chosen for the
      clinical phase. The clinical evaluation included performing both of these imaging protocols
      for patients with suspected uncomplicated acute appendicitis evaluated by a senior digestive
      surgeon. All of the enrolled patients underwent laparoscopic appendectomy to evaluate the
      sensitivity and specificity of the imaging protocols. The most optimal imaging protocols were
      selected for use in the APPAC II trial; one low-dose CT protocol for patients with BMI under
      30 and one optimised standard CT protocol for patients with BMI exceeding 30.

      For over a century appendectomy has been the standard treatment for all patients with acute
      appendicitis. However, the results of our APPAC trial have now shown that the majority (73%)
      of patients with uncomplicated acute appendicitis were successfully treated with antibiotics
      alone. We also showed that none of the patients treated initially with antibiotics and later
      undergoing appendectomy had major complications or increased morbidity defining antibiotic
      therapy as a safe first-line treatment. Patients with a complicated acute appendicitis
      require emergency appendectomy and early identification of these patients is of vital
      importance. Laparoscopic appendectomy has become the golden standard for appendectomy
      providing lower morbidity and faster recovery compared with open appendectomy. For patients
      with uncomplicated acute appendicitis, the time has come to evaluate abandoning routine
      appendectomy and evaluating the optimal use of antibiotic therapy.

      The aim of study is to optimize the antibiotic therapy for uncomplicated acute appendicitis
      by evaluating the success of treatment in both study groups and by comparing intravenous
      antibiotic therapy followed by per oral antibiotics with per oral antibiotic monotherapy. The
      study hypothesis is that broad-spectrum intravenous antibiotics requiring additional hospital
      resources are not necessary for the treatment of uncomplicated acute appendicitis and that
      per oral monotherapy is non-inferior to the combination of intravenous and per oral
      antibiotic therapy. The secondary aim is to evaluate the results of the randomized APPAC
      trial in a prospective patient cohort by implementing antibiotic therapy as the first-line
      treatment for uncomplicated acute appendicitis in clinical practice.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open-label
measure: Treatment success
time frame: 1 year
description: The resolution of acute uncomplicated appendicitis with allocated antibiotic treatment. Treatment success is defined as discharge from the hospital without the need for surgical intervention after the primary hospitalisation and no recurrent appendicitis during one-year follow-up.
measure: Late recurrence of appendicitis after antibiotic treatment
time frame: 1 year
description: Recurring appendicitis after primary treatment considered successful, thus recurrence after one year
measure: Duration of hospital stay
time frame: 1 month
description: Hospital stay
measure: Post-intervention complications
time frame: 10 years
description: Complications according to the Clavien-Dindo classification
measure: VAS pain score (visual analogue score)
time frame: 10 years
description: Pain as described with a scale from 0-10
measure: Sick leave
time frame: 1 month
description: Duration of sick leave
measure: Treatment costs
time frame: 1 year
description: Treatment costs including hospital stay costs, medicinal costs, imaging costs, costs to treat possible complications, operative costs
arm group label: Intravenous & per oral antibiotics
arm group type: Active Comparator
description: Ertapenem 1 g x 1 for two days i.v. followed by p.o. levofloxacin 500 mg x 1 and metronidazole 500 mg x 3 for 5 days, duration of treatment one week.
arm group label: Per oral antibiotics
arm group type: Active Comparator
description: Moxifloxacin 400 mg x 1 foe seven days, duration of treatment one week.
intervention type: Drug
intervention name: Ertapenem
description: I.v. ertapenem 1 g for 2 days followed by p.o. levofloxacin 500 mg x1 and metronidazole 500 mg x 3 for 5 days
arm group label: Intravenous & per oral antibiotics
other name: Levofloxacin
other name: Metronidazole
intervention type: Drug
intervention name: Moxifloxacin
description: P.o. moxifloxacin 400 mg x1 for 7 days
arm group label: Per oral antibiotics
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Paulina Salminen, MD, PhD
role: Principal Investigator
affiliation: Turku University Hospital
facility: 
country: Finland
responsible party type: Principal Investigator
investigator affiliation: Turku University Hospital
investigator full name: Paulina Salminen
investigator title: MD, PhD
mesh term: Appendicitis
mesh term: Acute Disease
mesh term: Moxifloxacin
mesh term: Metronidazole
mesh term: Levofloxacin
mesh term: Ertapenem
sharing ipd: No