Savino 1994.

Methods	Monocentre, randomized study with four groups of allocation Duration of the study: July 1990 to December 1991 Patients excluded/patients randomized: 0/292 (0%) Sample size calculation/method description: No/No
Participants	Patients randomized: 292 Age (mean): 54 years (clotrimazole group), 57 years (ketoconazole group), 53 years (nystatin group), 54 years (no intervention) Sex: 166 men, 126 women Inclusion criteria: expected length of stay > 48 hours Exclusion criteria: patients suffered from burn injury, underwent transplant, had received systemic antifungal agents within two weeks of the study, had evidence of a pre‐existing systemic fungal infection or yeast colonization, pregnant women Percentage post‐surgical: 79% Percentage colonized with Candida at baseline: not stated
Interventions	1. Clotrimazole 30 mg/day orally (n = 80). 2. Ketoconazole 200 mg/day orally (n = 65) 3. Nystatin 2 million units every six hours (n = 75) 4. No intervention (n = 72) Duration of the intervention: until ICU discharge
Outcomes	Mortality Proven IFI Fungal colonization Follow‐up duration: not stated
Type of antifungal treatment	Prophylaxis
Funding sources	Not reported
Declaration of interest among the primary researchers	Not reported
Notes	Country: USA Setting: single centre, adult surgical ICU Other: Study not included in the quantitative analysis due to high risk of bias in key domains
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Random assignment of patients to one of the four group was accomplished by drawing a sealed envelope sequentially from a box” Comment: it was not clear to us what authors meant describing the randomization process
Allocation concealment (selection bias)	High risk	Quote: “Patients assigned to group III, or ketoconazole, were not given ketoconazole if they had known sensitivity to ketoconazole, a current history of hepatitis or hepatic cirrhosis, or evidence of hepatic dysfunctions… Assignment of these patients to one of the three remaining groups was made by drawing the next envelope” Comment: if the patient presented the conditions described by the authors and he/she was assigned to ketoconazole group, a selection bias could occur because the patient would be assigned to another group
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: no blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: insufficient information about blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no missing data outcome. All patients who were randomized were included in the final analysis
Selective reporting (reporting bias)	Low risk	Comment: the study protocol was not available but it was clear that the published report include all expected outcomes
Other bias	High risk	Comment: the study had a potential source of bias due to the specific study design (patients with altered liver function were allocated only in groups I, II and III, leading to a potential unbalanced allocation of critically ill patients