BackgroundAntibiotic-associated diarrhoea (AAD) is a frequent complication of systemic antibiotic therapy and Clostridium difficile-associated diarrhoea (CDAD) is its most serious form due to associated morbidity and mortality.AimThis trial aimed to investigate whether the probiotic VSL#3 prevents AAD and CDAD in average-risk hospital patients.MethodsAdult hospital inpatients exposed to systemic antibiotics were recruited to this multicentre, randomized, double-blind, placebo-controlled trial. One sachet of VSL#3 or placebo was given twice daily for the length of the antibiotics course and for seven days thereafter. Primary outcomes were AAD and CDAD.FindingsPatients randomized to active (N = 117) and placebo (N = 112) groups were well-matched for baseline demographic patient data. No cases of CDAD were detected. The rate of AAD was significantly lower in the active group on per protocol analysis (0% active vs 11.4% placebo; P = 0.006). On intention-to-treat analysis the difference in AAD incidence (4.3% active vs 8.9% placebo; P = 0.19) was not significant.ConclusionsVSL#3 is associated with a significant reduction in the incidence of AAD in average-risk hospital inpatients exposed to systemic antibiotics. As the incidence of CDAD has fallen sharply, no cases of CDAD were found. Probiotic administration as prophylaxis for CDAD may not be indicated in average-risk hospital patients.

Introduction CDAD is the most common health care-acquired infection in the United Kingdom and causes significant morbidity and mortality. Previous studies have reported incidences of CDAD as high as 17%. Prevention of CDAD by Probiotics co-administration during antibiotic exposure is an appealing concept, but the few previously published trials showed inconclusive data and were hindered by flaws in trial design. This trial aims to investigate whether VSL#3 will prevent AAD and CDAD in hospitalised patients exposed to systemic antibiotics. Methods This multi-centre, randomised, double-blind, placebo-controlled trial will recruit 445 patients. One sachet of VSL#3 or placebo is given twice daily for the length of the antibiotics course and 7 days thereafter with follow-up for 28 days after the last antibiotic dose. Primary outcomes are occurrence of AAD and CDAD and secondary outcomes are length of stay (LOS) and 30-day mortality. Results This interim analysis reports on 124 patients enrolled in the trial so far. 62 patients were randomised to the active and 62 to the placebo group. Both groups were well matched for baseline demographic patient data. The study drug was generally well tolerated, and there was no difference in the rate of serious adverse events (3 in each group). Exposure to high risk antibiotic regimens was 85.5% (active) and 74.4% (placebo), respectively. No statistically significant differences were found in primary and secondary outcomes between the active and the placebo group at interim analysis. There was, however, a trend towards less AAD in the active group on per protocol analysis (active 0%, placebo 11.4%, p = 0.11). Assuming CDAD incidences of 5% in the placebo group and 0.1% in the active group 175 participants per group (350 in total) would give 90% power to detect a difference at a significance level of 0.05. Table 1 OC-007 Results of the interim per protocol (PP) analysis Active group (PP) Placebo group (PP) p-Value (PP) AAD 0 4 (11.4%) p = 0.11 CDAD 0 0 p = 1.0 LOS (days) 8 10.2 p = 0.31 30-day mortality 0 0 p = 1.0 Conclusion VSL#3 is well tolerated, and no drug-related SAE were reported. The incidences of both AAD and CDAD are much lower than previously reported. This may reflect improved infection control measures (hygiene, isolation rooms, and antibiotic policy) at the participating sites. Updated power calculations based on the lower incidences find that the original sample size is still suitable to confirm or refute the primary hypothesis.

We performed a randomised controlled trial (RCT) to determine whether risedronate 35 mg once weekly prevents bone loss following an 8-week reducing course of prednisolone given for an exacerbation of inflammatory bowel disease (IBD). The greatest change in bone mineral density (BMD) was at Ward’s triangle (WT), which fell by 2.2% in the placebo group, compared with a reduction of 0.8% in the risedronate group.