Background
Emergency appendectomy for acute appendicitis (AA) is an effective and universally accepted procedure performed more than 300,000 times annually in the United States. The life-time risk to have AA is 8.6% in men and 6.7% in women; the risk for emergency appendectomy is 12% and 23%, respectively. In Finland, approximately 6,500 appendectomies are performed annually with a mean hospital stay of 2.7 days. For over a century it has been generally believed that AA progresses invariably from early inflammation to later gangrene and perforation, and that emergency appendectomy is always required for surgical source control.
Although non-operative management with antibiotics of uncomplicated acute diverticulitis and salpingitis has been well established, the non-operative management of AA remains controversial. There is one Cochrane analysis, five meta-analysis and some reviews of non-operative treatment of AA. Although a non-surgical approach in AA may reduce the complication rate, the lower efficacy may prevent antibiotic therapy from being a first-hand alternative to surgery. On the other hand, appendectomy may not be always necessary for the patients with uncomplicated AA, as many patients resolve spontaneously and others may be treated with antibiotic therapy. Six randomized controlled trials (RCTs) have compared the efficacy of antibiotic therapy with surgery in the treatment of AA.
Abdominal computed tomography (CT) is the best non-invasive diagnostic tool available and it has become more commonly used in this respect for patients with AA with a high sensitivity and specificity. Most previous RCTs comparing antibiotic therapy with surgery in the management of AA are lacking abdominal CT to confirm AA. Therefore, a well-designed controlled trial comparing non-operative management versus early appendectomy for uncomplicated AA corroborated by CT imaging has been called for. CT scan is used in the APPAC trial for research purposes as CT scan confirmed uncomplicated acute appendicitis will prevent bias in our result as the antibiotic group patients are also treated for acute appendicitis enabling accurate comparison with the surgery group. The only previous study of antibiotic treatment in CT scan diagnosed AA indicated that amoxicillin/clavulanic acid was not non-inferior to emergency appendectomy in the treatment of AA, but identification of predictive markers, such as appendicolith, on CT scans might enable improved targeting of antibiotic treatment. CT scanning of patients with suspected AA has been considered essential to exclude non-appendicitis and to identify perforated appendicitis or an appendiceal abscess reducing the number of non-therapeutic appendectomies and overall admission costs. Meta-analysis and review articles suggest that although antibiotics may be used as the primary treatment for selected patients with suspected uncomplicated AA, this is unlikely to supersede appendectomy at present. The recent meta-analysis by Mason et al. identified non-operative management of uncomplicated AA to be associated with significantly fewer complications, better pain control and shorter sick leave, but overall having inferior efficacy because of high rate of recurrence (10 – 20%) in comparison with appendectomy.
Objective
The objective of the APPAC trial is to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of CT scan confirmed uncomplicated AA. The overall objective of the study is to provide level I evidence to support the hypothesis that approximately 75–85% of patients with uncomplicated AA can be treated without surgery by using effective antibiotic therapy.
The primary endpoint will be the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain VAS-scores.