Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial)

Abstract

BackgroundBased on epidemiological and clinical data acute appendicitis can present either as uncomplicated (70–80%) or complicated (20–30%) disease. Recent studies have shown that antibiotic therapy is both safe and cost-effective for a CT-scan confirmed uncomplicated acute appendicitis. However, based on the study protocols to ensure patient safety, these randomised studies used mainly broad-spectrum intravenous antibiotics requiring additional hospital resources and prolonged hospital stay. As we now know that antibiotic therapy for uncomplicated acute appendicitis is feasible and safe, further studies evaluating optimisation of the antibiotic treatment regarding both antibiotic spectrum and shorter hospital stay are needed to evaluate antibiotics as the first-line treatment for uncomplicated acute appendicitis.MethodsAPPAC II trial is a multicentre, open-label, non-inferiority randomised controlled trial comparing per oral (p.o.) antibiotic monotherapy with intravenous (i.v.) antibiotic therapy followed by p.o. antibiotics in the treatment of CT-scan confirmed uncomplicated acute appendicitis. Adult patients with CT-scan diagnosed uncomplicated acute appendicitis will be enrolled in nine Finnish hospitals. The intended sample size is 552 patients.Primary endpoint is the success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without the need for surgical intervention and no recurrent appendicitis during one-year follow-up. Secondary endpoints include post-intervention complications, late recurrence of acute appendicitis after one year, duration of hospital stay, pain, quality of life, sick leave and treatment costs. Primary endpoint will be evaluated in two stages: point estimates with 95% confidence interval (CI) will be calculated for both groups and proportion difference between groups with 95% CI will be calculated and evaluated based on 6 percentage point non-inferiority margin.DiscussionTo our knowledge, APPAC II trial is the first randomised controlled trial comparing per oral antibiotic monotherapy with intravenous antibiotic therapy continued by per oral antibiotics in the treatment of uncomplicated acute appendicitis. The APPAC II trial aims to add clinical evidence on the debated role of antibiotics as the first-line treatment for a CT-confirmed uncomplicated acute appendicitis as well as to optimise the non-operative treatment for uncomplicated acute appendicitis.Trial registrationClinicaltrials.gov, NCT03236961, retrospectively registered on the 2nd of August 2017.

Suspected appendicitis and COVID-19, a change in investigation and management—a multicentre cohort study

“…There is however evidence to suggest that supportive care alone without antibiotics is a safe alternative [30]. We await the results of the APPAC II [31] and III [32] trials, which we hope will provide an optimal evidence-based non-operative strategy.…”

Prospective multicentre cohort trial on acute appendicitis and microbiota, aetiology and effects of antimicrobial treatment: study protocol for the MAPPAC (Microbiology APPendicitis ACuta) trial

“…monotherapy in the treatment of uncomplicated acute appendicitis (NCT03236961). 33 APPAC III trial is a randomised double-blind, placebo-controlled, superiority multicentre study to compare antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis (NCT03234296). 34 All incoming patients are informed of all ongoing trials.…”

Antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: Changes in treatment modalities related to the COVID-19 health crisis

“…As the outcomes reported by Vons et al appear no worse than that of the other studies (Table 1), oral administration of antibiotics seems reasonable and acceptable as long as the patient is not nauseated and does not vomit. A noninferiority randomized trial (APAC II) is currently underway to compare the efficacy of IV followed by oral administration vs initial oral administration [31].…”