Kruis 1997.

Study characteristics
Methods	Double‐blind, multicentre RCT Setting: outpatient hospitals and private practices in Germany, the Czech Republic and Austria Study period: not stated
Participants	Inclusion: age > 17 years; presence of chronic UC currently in remission (defined by CAI score) Exclusion: active UC, infectious colitis, existing or intended pregnancy, any other medication for UC besides the study drugs, antibiotics or suphonamides, substantial cardiac, hepatic or renal disease, major operations on the bowels, and known intolerance to salicylates Age* (range): 19 to 88 years Sex* (M/F): 55/48 Site of disease*: 28 (proctitis); 40 (proctosigmoiditis); 19 (left‐sided colitis); 18 (total/subtotal colitis) Use of medication*: 82 (salicylates); 25 (corticosteroids) Length of time remission at study entry: 14 (1 to 147 (probiotic)/12 (1 to 60) months (mesalazine) Number randomised (n = 120): 60? (probiotics)/60? (mesalazine) Number assessed: 50 (probiotics)/53 (mesalazine) Postrandomisation exclusion: 2 ‐ not started taking study medication, 15 ‐ had CAI of > 4 (8 versus 7)
Interventions	Probiotics + mesalazine placebo: oral preparation containing E coli strain Nissle 1917. 200 mg/day (day 1 to 4, only 100 mg/day) of a preparation of viable E coli strain Nissle 1917 (Mutaflor, Ardeypharm GmbH, Herdecke, Germany) taken as a single dose during breakfast. Mutaflor 100 mg contains 25 X 109 viable E coli bacteria Mesalazine + placebo: 500 mg mesalazine three times a day (Salofalk, Dr Falk Pharma GmbH, Freiburg, Germany) plus placebo indistinguishable from the E coli preparation
Outcomes	Duration of follow‐up: 12 weeks (in one centre the total study period was 24 weeks) Relapse defined as CAI > 4 Relapse‐free time Adverse events Withdrawal due to adverse events
Notes	Funding source: supported by Ardeypharm GmbH, Herdecke, Germany Declaration of interest: not reported. *Baseline characteristics reported do not account for participants who were excluded postrandomisation
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Participants were reportedly randomised, however, the method of randomisation was not adequately described
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blind double‐dummy. Both intervention arms included placebos.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Described as double‐blind double‐dummy, however, there was no specific information as to whether outcome assessment was blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT analysis (modified ITT) was partially applied as it failed to account for participants who were excluded postrandomisation. However, number and reasons for postrandomisation exclusion appear to have been equal across groups (16% versus 11%)
Selective reporting (reporting bias)	Low risk	Trial registration was not available, however, all expected outcomes were reported
Other bias	Low risk	No other apparent biases