SIDESTEP Study.

Methods	Design: randomised, double‐blinded, non‐inferiority trial, multicentred Follow‐up period: 10 days after the end of antibiotic therapy
Participants	N: 586 participants randomised Sex (%male): 63.14% Age (median (min‐max)): Intervention Group: 59 years (25‐90); Control Group: 57 years (22‐94) Inclusion criteria: adults with diabetes mellitus (type 1 or 2) with foot infection that did not extend above the knee Exclusion criteria: mild infections that did not require parenteral antibiotic therapy; infection caused by resistant pathogens; thermal burn; necrotizing fasciitis; osteomyelitis unless all the infected bone was removed within 48 h after initiating study therapy; infection complicated by prosthetic material; gangrenous tissue not removed; pregnancy; nursing; fertile women not using contraception; reaction to beta‐lactam antibiotic; need for additional antibacterial agents; secondary diabetes mellitus or impaired glucose tolerance; insufficient arterial perfusion requiring revascularization; rapidly progressive or terminal illness; dialysis; immunosuppression; corticosteroid therapy; abnormal liver function; haematocrit < 25%; haemoglobin < 8; platelet count < 75000; coagulation test altered; more than 24 h of systemic antibiotic therapy within the 72 h before study screening
Interventions	Intervention (n = 295): ertapenem 1 g iv once daily Control (n = 291): piperacillin/tazobactam 3.4 g iv every 6 h Treatment duration: minimum of 5 days, then oral amoxicillin‐clavulanate (875 mg/125 mg every 12 h) could be given until day 28
Outcomes	Primary outcome Favourable clinical response (cure or improvement) at discontinuation of iv treatment Secondary outcomes Favourable clinical response at the follow‐up assessment (10 days after the last dose of study antibiotic) Adverse effects to treatment
Notes	Funding source: study funded by Merck and Co; the sponsor participated in study design, data collection, data analysis, data interpretation, and writing of the report; 2 study authors were employees of the sponsor Other: participants with mild infections and with possible osteomyelitis were excluded Sample size calculation performed and reached Most of the participants received some oral antibiotic therapy after parenteral study medication Authors commented that the trial did not assess long‐term outcomes and this could have had an impact on the durability of infection resolution
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Blocks of computer‐generated allocation numbers provided by the manufacturer
Allocation concealment (selection bias)	High risk	An unblinded pharmacist randomised participants
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data, and their reasons, well reported and presented in a CONSORT flowchart. No differences between groups
Selective reporting (reporting bias)	High risk	Trial report did not report a secondary variable described in the protocol
Other bias	Unclear risk	N/A
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blinded. The intervention group was given a saline placebo every 6 h (double‐dummy). Quote: "The pharmacist was responsible for randomising participants (1:1 ratio), and prepared intravenous therapy to be administered by clinical personnel (unaware of treatment allocation)".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The clinical personnel, who were unaware of treatment allocation, assessed the study's outcomes