Kranjcec 2014.

Study characteristics
Methods	Study design Parallel, open‐label, 3‐arm RCT Study duration and follow‐up 6 months treatment, no further follow‐up (October 2010 to October 2012) Study type Prevention and treatment study
Participants	General information Country: Croatia Setting: single centre Inclusion criteria: women aged ≥ 18 years; acute cystitis; history of recurrent cystitis (at least 2 episodes in 6 months or 3 in 12 months) Exclusion criteria: pregnant or breastfeeding; symptoms of upper UTI; symptoms or systemic inflammatory response (fever > 38°C, WCC > 12,000); history of urinary tract anomalies, interstitial cystitis or diabetes; taking hormone therapy, contraception, or had previously received antibiotic prophylaxis Baseline characteristics Number: treatment group 1 (103); treatment group 2 (103); control group (102) Median age, range (years): treatment group 1 (49, 38 to 56); treatment group 2 (48, 29 to 58); control group (52, 38 to 56) Sex: 100% women Definition of UTI: based on 103 or more CFU/mL of clean voided midstream urine, and at least two of the following LUTS: dysuria, frequency, urgency, suprapubic pain, nocturia, and hematuria Co‐morbidities: post‐menopausal (146) Other information: most commonly isolated bacteria during acute cystitis phase was E. coli in 236 patients (76.6 %), followed by Enterococcus faecalis (17, 5.5 %), Klebsiella pneumoniae (12, 3.9 %), Streptococcus agalactiae (8, 2.6 %), Proteus mirabilis (7, 2.3 %), Citrobacter freundii (4, 1.3 %)
Interventions	Treatment group 1 D‐mannose: 2 g powder in 200 mL water Once/day for 6 months Treatment group 2 Nitrofurantoin: 50 mg antibiotic tablet Once/day for 6 months Control group No treatment for 6 months Co‐interventions or additional treatments None reported Follow‐up details None past 6 months of treatment
Outcomes	Outcomes reported at 6 months Number of patients without recurrent UTI Isolated bacteria in acute cystitis Median time from prophylactic therapy start to cystitis symptoms onset (days) median (IQR) Complications during prophylaxis
Notes	Trial registration: not reported A priori published protocol: not reported Funding: not reported Conflicts of interest: "all authors state that they have no conflict of interest"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients with less than 103 CFU/ml in urine culture and no LUTS were considered cured and were randomly divided by throwing the dice in one of the three groups according to the prophylaxis they would receive during the following 6 months"
Allocation concealment (selection bias)	High risk	Comment: appears the patients may have thrown their own dice for randomisation (also the study is open‐label study so unlikely that allocation was concealed)
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	Low risk	Comment: 0% lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	Trial registration: not reported A priori published protocol: not reported Comment: the outcomes planned in the methods were reported in the results, however, no report or access to a priori methods
Other bias	Unclear risk	Funding: not reported Conflicts of interest: "all authors state that they have no conflict of interest"