Complex and Simple Appendicitis: REstrictive or Liberal Postoperative Antibiotic eXposure (CASA RELAX) Using Desirability of Outcome Ranking and Response Adjusted for Duration of Antibiotic Risk: A Multicenter Bayesian Randomized Controlled Trial

Background: The optimal duration of antibiotic agents after appendectomy for simple or complicated (gangrenous or perforated) appendicitis is unknown. We performed a randomized trial to compare a Restrictive to a Liberal post-operative antibiotic strategy, after appendectomy. Methods: Adults undergoing appendectomy were randomized 1:1 to a Restrictive (no post-operative antibiotic agents for simple, up to 1 d for complicated) or Liberal (up to 1 d for simple, 4 d for complicated) strategy. The primary endpoint was on the basis of Desirability of Outcome Ranking (DOOR)/Response Adjusted for Duration of Antibiotic Risk (RADAR), an ordinal scale of mutually exclusive clinical complications with within-category rankings determined by duration of antibiotic exposure. Bayesian cumulative logistic models using a neutral prior were used to assess the Posterior probability (PP) of benefit with a Restrictive strategy. Type of appendicitis (simple vs. complicated) was assessed as an interaction. Results: A total of 346 subjects enrolled from 9 sites were included in the final analysis. Baseline demographics between groups were similar. There were 265 simple and 81 complicated (11 gangrenous) appendicitis cases. The Restrictive strategy, had a cumulative odds ratio of 0.84 (95% credible interval [CrI] 0.42–1.72), a 68% PP that Restrictive tactic reduces (improves) the DOOR category. This was driven by patients with complicated appendicitis with an OR 0.69 (95% CrI: 0.27–1.68), a 79% probability that the Restrictive strategy, reduces DOOR. In the RADAR analysis, the Restrictive strategy, had an 80% PP of a more desirable overall outcome compared with the Liberal strategy. Conclusions: A restrictive post-operative antibiotic strategy, in acute appendicitis resulted in similar to mildly improved clinical outcomes, when compared with a Liberal strategy. The patients who benefitted most from a Restrictive strategy, were patients with complicated appendicitis.