STIC Study.

Methods	Design: Multicentre, multinational, non‐inferiority RCT (74 centres, 12 countries) Follow‐up period: 14‐28 days
Participants	N: 804 participants randomised; 134 participants with DFI For all included participants: Sex (%male): 60.6% Age (mean): Intervention Group: 52.1 years; Control Group: 51.0 years Inclusion criteria: ≥ 18 years with a cSSSI or SSSI (DFI, necrotizing fasciitis, post‐surgical wound infection, complicated cellulitis, complicated erysipelas, major abscess of the skin, infection of traumatic lesion, and infected ischaemic ulcer) at one site only; requiring systemic antimicrobial therapy; sample culture taken within 24 h prior to inclusion Exclusion criteria: uncomplicated mild‐to‐moderate SSSIs; secondary infected burns; atopic dermatitis; eczema; pregnancy; nursing; life expectancy < 2 months; end‐stage liver cirrhosis; dialysis; septic shock; chronic immunosuppressant treatment; neutropenia ≤ 1000 cells/ml; AIDS with CD4 < 200 cells/μl; HIV with highly activated antiretroviral treatment; syndromes of QTc prolongation or medication that increases the QTc; hypersensitivity to study drugs; tendinopathy with quinolones; SSSI secondary to prosthetic materials; > 18% of the skin and soft tissue affected; osteomyelitis not related to DFI; requirement for systemic concomitant antibacterial agents; failure to respond to previous antibacterial treatment if it contained a fluoroquinolone, amoxicillin or a beta‐lactam/beta‐lactamase inhibitor combination; systemic antibacterial treatment for > 24 h within the 24 h before enrolment
Interventions	Intervention (n = 63)::moxifloxacin 400 mg once daily iv followed by moxifloxacin 400 mg once daily po. Control (n = 71): amoxicillin‐clavulanate 1000 mg/200 mg iv every 8 h followed by amoxicillin‐clavulanate 500 mg/125 mg po every 8 h Switch from iv to po therapy was decided by the investigator based on clinical response Treatment duration: iv for at least 3 days; po for 7‐21 days Co‐interventions: surgery at investigator's discretion
Outcomes	Primary outcome Clinical response at the TOC visit (14‐28 days) Secondary outcome Bacteriological response Safety
Notes	Financial source: Bayer; 4 authors were employees of Bayer Other: sample size calculation not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The study was defined as randomised. No additional data described
Allocation concealment (selection bias)	Unclear risk	The study was defined as randomised. No additional data described
Incomplete outcome data (attrition bias) All outcomes	Low risk	No sample size calculation described. Reasons for withdrawal were described and there were no differences between groups (P value > 0.1) Failures were carried forward for the efficacy analysis; ITT and per protocol analysis
Selective reporting (reporting bias)	Unclear risk	Only data on TOC assessment (14‐28 days) reported. Other assessments were made but not reported: prior to therapy, during treatment (days 1‐3), and day of switch to po
Other bias	Unclear risk	NA
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Evaluations were performed by investigators (unblinded)