RESEARCH

APPAC I

The initial APPAC trial, conducted from November 2009 to June 2012, compared antibiotic therapy with appendectomy in the treatment of CT-confirmed uncomplicated acute appendicitis. The APPAC trial was a multicenter, randomized, open-label, non-inferiority trial conducted in Finland enrolling 530 patients 18 to 60 years of age with uncomplicated acute appendicitis. The majority of patients with uncomplicated acute appendicitis were successfully treated with antibiotics. None of the patients, who initially were treated with antibiotics that later had appendectomy, had major complications. Our results suggested that CT-proven uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe first-line treatment of uncomplicated acute appendicitis. The landmark nature of this ambitious trial was recognized by the selections as one of the Top 10 articles of the decade 2010–2019: most important to clinical medicine and public health

APPAC II

The randomized, clinical, multicenter APPAC II non-inferiority trial by our APPAC study group (conducted in nine Finnish hospitals) compared oral antibiotic monotherapy with a combination of similar-spectrum intravenous antibiotics followed by oral antibiotics in the management of CT-confirmed uncomplicated acute appendicitis. The trial enrolled 599 patients between April 2017 and November 2018. The APPAC II trial assessed the safety and efficacy of oral antibiotics, which were similar to intravenous followed by oral antibiotics allowing the future trials to assess outpatient treatment with only orally administered antibiotics.

APPAC III

The APPAC III trial is a double-blind, placebo-controlled, superiority, randomized APPAC III pilot feasibility trial conducted at all five university hospitals in Finland to assess the role of antibiotics in uncomplicated acute appendicitis. The lack of antibiotic superiority in this APPAC III trial suggests that even antibiotics may not be necessary for uncomplicated acute appendicitis and a large non-inferiority trial against placebo (APPAC IV) is warranted in adults with CT-confirmed uncomplicated acute appendicitis.

MAPPAC I & II

The original MAPPAC  (Microbiology APPendicitis  Acuta) is designed as a prospective trial with two arms. The single center arm aims to determine the possible differences in the etiology of complicated and uncomplicated acute appendicitis with a special reference to the role of appendicoliths. The multicenter arm focuses on investigating possible  immunological and  microbiological factors involved in appendicitis recurrence, the effects of antibiotic treatment and placebo on gut microbiota as well as the duration of the hospital stay on the possible antimicrobial resistance within gut microbiota.

APPAC IV

Building on our previous trials, the APPAC IV trials has been designed as a randomized double-blind multicenter clinical trial comparing once daily oral moxifloxacin with placebo in an outpatient setting aims to evaluate whether antibiotics and hospitalization or both can be omitted in the treatment of uncomplicated appendicitis further significantly increasing cost savings and patient satisfaction.

To achieve this, the APPAC IV study has four specific Aims:

1. Can antibiotics be omitted in the treatment of uncomplicated acute appendicitis?
2. Is outpatient treatment of uncomplicated acute appendicitis safe – can hospitalization be avoided?
3. The effect of oral antibiotics on gut microbiota and antibiotic resistance (Microbiology APPAC II)
4. The effect of oral antibiotics on gut microbiota and correlation to serum cytokines (MAPPAC II)

RESEARCH MATERIALS