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
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||147 participants|
|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.|
|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|
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.
Intravenous antibiotic followed by per oral antibiotics
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.
Intravenous placebo followed by per oral placebo
- 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.
- 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
- Post-intervention complications [ Time Frame: 10 years ]Complications according to the Clavien-Dindo classification
- Hospital stay [ Time Frame: 1 month ]Duration of hospital stay in days
- VAS score (visual analogue score) [ Time Frame: 10 years ]Pain as defied by the VAS pain score
- Sick leave [ Time Frame: 1 month ]Duration of sick leave
- 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
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
|Turku University Hospital|
|Principal Investigator:||Paulina Salminen, MD,PhD||Turku University Hospital|