Arbeit 2004.

Methods	Design: 2 identical multicentre, international, phase III randomised trials; non inferiority trial Follow‐up period: 28 days
Participants	N: 1092 For the diabetic participants subgroup, the data came from Lipsky 2005: N:133 Sex (%male): 54% Age (mean): Intervention Group: 60 years; Control Group: 63 years Inclusion criteria: people with diabetes; between the ages of 18‐85 years; requiring hospitalisation for an infected ulcer that was known or suspected to be caused by a Gram‐positive organism (based on a Gram‐stained smear) Exclusion criteria: minor or superficial skin infections; uncomplicated cellulitis; myositis; multiple infected ulcers at distant sites; infected third‐degree burn wounds; osteomyelitis; known bacteraemic shock; hypotension, or any disorder that could interfere with the treatment evaluation; pregnancy; infection due to an organism known to be resistant to any study drug; < 40 kg in weight; hypersensitivity reaction to study drugs; haemodialysis or peritoneal dialysis; impaired renal function (creatinine clearance < 30 mL/min); immunosuppression; serum creatine phosphokinase > 50% above the upper limit of normal; statin use; systemic antibiotic treatment for more than 24 h within the previous 48 h (unless the infecting Gram‐positive organism was resistant to that therapy, or it was clinically ineffective)
Interventions	Intervention (n = 61): daptomycin 4 mg/kg iv every 24 h over 30 minutes Control (n = 72): preselected comparator (previous to randomizations) based on the investigator’s assessment of the participant’s likelihood of infection with MRSA: either vancomycin 1 g iv every 12 h over 60 minutes or a semi‐synthetic penicillin (nafcillin, oxacillin, cloxacillin or flucloxacillin, according to the investigator’s choice) The investigator could add aztreonam to cover Gram‐negative bacteria if they were suspected or proven to be part of a polymicrobial infection, or metronidazole to cover possible or proven infection with obligate anaerobic bacteria Treatment duration: 7‐14 days
Outcomes	Primary outcome Rate of clinical success in treating the diabetic foot infection Secondary outcome Rate of microbiological success in eradicating the causative pathogen(s)
Notes	Funding source: Cubist Pharmaceuticals (makers of daptomycin); 4 authors were employees of Cubist Pharmaceuticals, and the other was an investigator for Cubist clinical trials Other: no sample size calculation. This was a subgroup analysis of another RCT
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as a randomised study, but no information provided about the sequence generation
Allocation concealment (selection bias)	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	High risk	30 participants were not clinically evaluable (22.5%) with no differences between the study groups. The reasons were not explained
Selective reporting (reporting bias)	Low risk	All outcomes mentioned in the methods section were also reported in results section.
Other bias	High risk	This study was a subgroup analysis of another study so it was not big enough to identify differences between the comparison groups. The original study recruited 1092 participant with a power of 80% to detect non‐inferiority
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No information provided
Blinding of outcome assessment (detection bias) All outcomes	Low risk	A blinded investigator categorized the clinical outcome