BackgroundComputerised decision-support systems (CDSSs) for antibiotic stewardship could help to assist physicians in the appropriate prescribing of antibiotics. However, high-quality evidence for their effect on the quantity and quality of antibiotic use remains scarce. The aim of our study was to assess whether a computerised decision support for antimicrobial stewardship combined with feedback on prescribing indicators can reduce antimicrobial prescriptions for adults admitted to hospital.MethodsThe Computerised Antibiotic Stewardship Study (COMPASS) was a multicentre, cluster-randomised, parallel-group, open-label superiority trial that aimed to assess whether a multimodal computerised antibiotic-stewardship intervention is effective in reducing antibiotic use for adults admitted to hospital. After pairwise matching, 24 wards in three Swiss tertiary-care and secondary-care hospitals were randomised (1:1) to the CDSS intervention or to standard antibiotic stewardship measures using an online random sequence generator. The multimodal intervention consisted of a CDSS providing support for choice, duration, and re-evaluation of antimicrobial therapy, and feedback on antimicrobial prescribing quality. The primary outcome was overall systemic antibiotic use measured in days of therapy per admission, using adjusted-hurdle negative-binomial mixed-effects models. The analysis was done by intention to treat and per protocol. The study was registered with ClinicalTrials.gov (identifier NCT03120975).Findings24 clusters (16 at Geneva University Hospitals and eight at Ticino Regional Hospitals) were eligible and randomly assigned to control or intervention between Oct 1, 2018, and Dec 31, 2019. Overall, 4578 (40·2%) of 11 384 admissions received antibiotic therapy in the intervention group and 4142 (42·8%) of 9673 in the control group. The unadjusted overall mean days of therapy per admission was slightly lower in the intervention group than in the control group (3·2 days of therapy per admission, SD 6·2, vs 3·5 days of therapy per admission, SD 6·8; p<0·0001), and was similar among patients receiving antibiotics (7·9 days of therapy per admission, SD 7·6, vs 8·1 days of therapy per admission, SD 8·4; p=0·50). After adjusting for confounders, there was no statistically significant difference between groups for the odds of an admission receiving antibiotics (odds ratio [OR] for intervention vs control 1·12, 95% CI 0·94–1·33). For admissions with antibiotic exposure, days of therapy per admission were also similar (incidence rate ratio 0·98, 95% CI 0·90–1·07). Overall, the CDSS was used at least once in 3466 (75·7%) of 4578 admissions with any antibiotic prescription, but from the first day of antibiotic treatment for only 1602 (58·9%) of 2721 admissions in Geneva. For those for whom the CDSS was not used from the first day, mean time to use of CDSS was 8·9 days. Based on the manual review of 1195 randomly selected charts, transition from intravenous to oral therapy was significantly more frequent in the intervention group after adjusting for confounders (154 [76·6%] of 201 vs 187 [87%] of 215, +10·4%; OR 1·9, 95% CI 1·1–3·3). Consultations by infectious disease specialists were less frequent in the intervention group (388 [13·4%] of 2889) versus the control group (405 [16·9%] of 2390; OR 0·84, 95% CI 0·59–1·25).InterpretationAn integrated multimodal computerised antibiotic stewardship intervention did not significantly reduce overall antibiotic use, the primary outcome of the study. Contributing factors were probably insufficient uptake, a setting with relatively low antibiotic use at baseline, and delays between ward admission and first CDSS use.FundingSwiss National Science Foundation.TranslationsFor the French and Italian translations of the abstract see Supplementary Materials section.