Comparing Placebo versus Antibiotics for Acute Uncomplicated Diverticulitis

About This Grant

PROJECT SUMMARY/ABSTRACT Diverticulitis is a disease marked by inflammation of diverticula in the colon. In the US, it is highly prevalent and costly, accounting for more than 2.6 million outpatient visits (combined emergency department and ambulatory clinic) and 200,000 inpatient admissions for diverticulitis at a cost of more than $2 billion. Patients can present with a wide spectrum of disease severity, from localized inflammation (uncomplicated) to frank perforation (complicated). Traditionally in the US, treatment for acute uncomplicated diverticulitis (AUD) has been antibiotic therapy. However, antibiotics can have significant side effects, both on the patient and population level. Patients can experience side effects as well as life-threatening superinfections. At the population level, inappropriate antibiotic use is the primary driver of antimicrobial resistance (AMR), a critical national and global threat. Results from recent studies conducted in Europe suggest that antibiotics may be unnecessary to treat mild acute diverticulitis. However, these trials have significant flaws and concerning trends in secondary outcomes which have limited implementation in a US population. Additionally, the US population differs fundamentally from the European population in race and ethnicity as well as the effect of socioeconomic drivers of health. A recent study cites the lack of US data as the strongest barrier to implementation. This knowledge gap – whether antibiotics improve recovery from AUD in current US clinical practice – leads to the proposal of a pilot, randomized trial of placebo versus antibiotic treatment of AUD in 100 patients with oversampling based on race and ethnicity. We aim to 1) determine differential rates of recruitment, treatment acceptance/adherence, cross-over, clinical endpoint assessment compliance and loss to follow-up at 30 days and 6 months by race and ethnicity to assess feasibility of a large scale, multicenter trial. 2) acquire preliminary data regarding the effects of a placebo compared to antibiotics for AUD on a range of key patient-centric efficacy and safety endpoints These results will inform the design, sample size, and endpoint selection for the subsequent efficacy trial that will generate critical evidence to assess the role of antibiotics in the treatment of AUD. This proposal is an outstanding fit for PAS-23-086 (Small R01s for Clinical Trials Targeting Diseases within the Mission of NIDDK). This small, short-term clinical trial in humans will acquire preliminary data regarding the effects of non-antibiotic management of acute, uncomplicated diverticulitis, as well as feasibility data related to recruitment and retention, and study conduct. Completion of this award will lay the foundation for larger, multicenter clinical trials to further our understanding of the optimal role of antibiotics in the management of acute uncomplicated diverticulitis.