Porru 2014.

Study characteristics
Methods	Study design Cross‐over, open‐label RCT After 24 weeks of treatment, patients switched groups for another 24 weeks, with no washout period Study duration and follow‐up 6 months treatment, 12 months follow‐up (study dates not reported) Study type Prevention and treatment study
Participants	General information Country: Italy Setting: single centre Inclusion criteria: females ≥ 18 years; acute symptomatic UTI and 3 or more UTIs with culture of midstream urine specimen in last 12 months; no antimicrobials in last 4 weeks Exclusion criteria: pregnant; upper UTI and/or temp > 38°C; flank/lumbar pain or tenderness; kidney disease; anatomical abnormalities; gynaecological surgery; immunosuppressive medications or disease Baseline characteristics Number: 60 Mean age (range): 42 years (22 to 54) Sex: 100% women Definition of UTI: acute flare of urinary symptoms + positive voided urine culture with at least 100,000 uropathogens/mL (24‐hour voiding diary) Co‐morbidities: irritable bowel syndrome (5); constipation (26)
Interventions	Treatment group D‐mannose: 1 g tablets 3/day for 2 weeks, then 2/day for 22 weeks Control group Oral antibiotics: trimethoprim 160 mg + sulfamethoxazole 800 mg Twice/day, followed by a single dose at bedtime for 1 week each month in the following 22 weeks Co‐interventions or additional treatments "D‐mannose activity is best when urine has a neutral pH, patients were instructed to measure urinary pH using dipstick and take oral sodium bicarbonate 250 mg b.i.d or potassium citrate 1 g b.i.d as alkalising agents it pH was < 7" Follow‐up details 12 months
Outcomes	Outcomes reported at 24 weeks Time‐to‐recurrence of symptomatic bacteriuria: acute flare of urinary symptoms + positive voided urine culture with at least 100,000 uropathogens/mL (24‐hour voiding diary) Pain (VAS) Urgency per 24 hours (VAS)
Notes	A priori published protocol: not reported Funding: "this research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors" Conflicts of interest: "none declared"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "each participant entering the trial was assigned to one of the following treatments in a random sequence" Comment: insufficient details provided about the methods used to randomise to treatment groups
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided regarding the concealment of allocation to groups
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: open‐label study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Comment: open‐label study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: attrition and withdrawals not reported, unclear if any participants dropped out and if an intention‐to‐treat analysis was undertaken
Selective reporting (reporting bias)	Low risk	Trial registration: NCT01808755 A priori published protocol: not reported Comment: all outcomes planned in the methods were reported in the results, and the methodology matches the trial registration details
Other bias	Low risk	Funding: "this research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors" Conflicts of interest: "none declared"