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Antibiotics vs. Placebo in Acute Uncomplicated Appendicitis (APPACIII)

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ClinicalTrials.gov Identifier: NCT03234296
Recruitment Status : Enrolling by invitation
First Posted : July 31, 2017
Last Update Posted : April 9, 2018
Sponsor:
Collaborators:
Tampere University Hospital
Kuopio University Hospital
Oulu University Hospital
Helsinki University Central Hospital
Information provided by (Responsible Party):
Paulina Salminen, Turku University Hospital

Brief Summary:

Appendicectomy has been the treatment of acute appendicitis for over a hundred years. Appendicectomy, however, includes operative and postoperative risks despite being a "routine" operation. At the same time other similar intra-abdominal infections, such as diverticulitis, are treated with antibiotics. Several studies have proved promising results of the safety and efficiency of antibiotics in the treatment of acute uncomplicated appendicitis. Our previous APPAC study, published in 2015 in the Journal of American Medical Association, also proved promising results with 73% of patients with CT-diagnosed uncomplicated appendicitis treated successfully with antibiotics within one-year follow-up. 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.

Already in 1886 Fitz noted that 1/3 of patients in a large series of autopsies from the pre-appendicectomy era had evidence of prior appendices inflammation suggesting spontaneous resolution of acute appendicitis. Acute appendicitis is thought to be similar to acute diverticulitis ("left-sided appendicitis") and this similarity has been shown in epidemiological studies. Recent studies have shown no benefit of antibiotic treatment in the treatment of uncomplicated diverticulitis with outpatient management without antibiotics proving safe and well-functioning.

The aim of this randomised double-blinded study is to compare antibiotic therapy with placebo to evaluate the role of antibiotic therapy in the resolution of CT-diagnosed uncomplicated acute appendicitis.

The hypothesis is that antibiotic therapy is necessary in the treatment of acute uncomplicated appendicitis and that antibiotic therapy is superior to spontaneous resolution (placebo) with the primary endpoint evaluated at ten days after the intervention.


Condition or disease Intervention/treatment Phase
Acute Appendicitis Drug: Ertapenem Other: Placebo Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 147 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Anticipated enrollment delays > three alternate scenarios for sample size calculations, please see prtocol for details.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blinded RCT, no care providers, patients or researchers are aware of the randomised treatment. Separate safety monitoring committee and preplanned interim analysis.
Primary Purpose: Treatment
Official Title: Antibiotic Therapy vs. Placebo in the Treatment of Acute Uncomplicated Appendicitis: a Randomized Double-blinded Placebo-controlled Trial - APPAC III Study
Actual Study Start Date : August 9, 2017
Estimated Primary Completion Date : March 30, 2019
Estimated Study Completion Date : August 30, 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Ertapenem

Arm Intervention/treatment
Active Comparator: Antibiotic treatment
Ertapenem 1 g x 1 intravenously for 3 days, followed by per oral levofloxacin 500 mg x 1 and metronidazole 500 mg x 3 for 4 days, duration of treatment 7 days.
Drug: Ertapenem
Intravenous antibiotic followed by per oral antibiotics
Other Names:
  • Levofloxacin
  • Metronidazole

Active Comparator: Placebo
Intravenous placebo once a day for 3 days, followed by per oral placebo for 4 days with similar p.o. tablets as in the antibiotic group.
Other: Placebo
Intravenous placebo followed by per oral placebo




Primary Outcome Measures :
  1. Success of the randomized treatment [ Time Frame: 10 days after treatment initiation ]
    Resolution of acute appendicitis with study group treatment resulting in discharge from the hospital without the need for surgical intervention and treatment efficacy evaluated at ten days after initiation of the randomized treatment.


Secondary Outcome Measures :
  1. Late recurrence of appendicitis [ Time Frame: 10 years ]
    Late recurrence of acute appendicitis after study treatment defined as clear clinical suspicion of acute appendicitis evaluated at follow-up of one, three, five and ten years

  2. Post-intervention complications [ Time Frame: 10 years ]
    Complications according to the Clavien-Dindo classification

  3. Hospital stay [ Time Frame: 1 month ]
    Duration of hospital stay in days

  4. VAS score (visual analogue score) [ Time Frame: 10 years ]
    Pain as defied by the VAS pain score

  5. Sick leave [ Time Frame: 1 month ]
    Duration of sick leave

  6. Treatment costs [ Time Frame: 10 years ]
    Costs resulting from laboratory costs, imaging costs, treatments costs, hospital stay, and treatment of complications and possible operative treatment



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18-60 years
  • CT confirmed uncomplicated acute appendicitis
  • Ability to give informed consent

Exclusion Criteria:

  • Age under 18 or over 60 years
  • Pregnancy or lactation
  • Allergy to contrast media or iodine
  • Allergy or contraindication to antibiotic therapy
  • Metformin medication
  • Renal insufficiency
  • Severe systemic illness (for example malignancy, medical condition requiring immunosuppressant medication)
  • Complicated acute appendicitis confirmed by CT scan
  • Inability to cooperate or give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03234296


Locations
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Finland
Turku University Hospital
Turku, Finland
Sponsors and Collaborators
Turku University Hospital
Tampere University Hospital
Kuopio University Hospital
Oulu University Hospital
Helsinki University Central Hospital
Investigators
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Principal Investigator: Paulina Salminen, MD,PhD Turku University Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Paulina Salminen, Primary investigator, Turku University Hospital
ClinicalTrials.gov Identifier: NCT03234296     History of Changes
Other Study ID Numbers: APPAC III
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Paulina Salminen, Turku University Hospital:
uncomplicated acute appendicitis
complicated acute appendicitis
antibiotic therapy
spontaneous resolution

Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents, Urinary
Renal Agents
Antineoplastic Agents
Appendicitis
Acute Disease
Intraabdominal Infections
Infection
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cecal Diseases
Intestinal Diseases
Disease Attributes
Pathologic Processes
Metronidazole
Levofloxacin
Ofloxacin
Ertapenem
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors