Lauf 2014.

Methods	Design: multicentre, international, phase III randomised non inferiority trial. The study contained a sub study Follow‐up period: 25‐27 weeks after last dose of antibiotic
Participants	N of the main study: 955 N of the sub study: 118 Sex (main study; %male): 62.9 (tigecycline group); 67.5% (ertapenem group) Age (mean; main study): 59 years Inclusion criteria: hospitalised men and women; ≥ 18 years with diabetes mellitus; with a foot infection that did not extend above the knee. Infections of a PEDIS infection grade from 2 to 4 and a perfusion grade from 1 to 2, of acute onset or a worsening within 14 days prior; participants with osteomyelitis at baseline were not evaluable in the primary study but were included in the secondary study Exclusion criteria: participants receiving more than 48 h of a prior antibiotic treatment; necrotizing fasciitis; crepitant cellulitis; wet gangrene; gas gangrene; ecthyma gangrenosum; or implanted prosthetic material or devices that were not to be removed; infection known or suspected to be caused by a pathogen resistant to study drugs. Severely impaired arterial supply of the foot or requiring amputation within 1 month. Renal replacement therapy; plasmapheresis; hypersensitivity to study drugs; neutropenia or immunosuppressive treatment; creatinine clearance < 30 mL/min; hepatic disease; lactating women or fertile women not using contraception
Interventions	Intervention (n = 483): tigecycline 150 mg iv every 24 h ± placebo vancomycin Control (n = 472): ertapenem 1 g iv every 24 h ± vancomycin Treatment duration: 28 days for the main study and 42 days for sub study in participants with osteomyelitis
Outcomes	Primary outcome Clinical response at TOC visit (12‐92 days) in participants without osteomyelitis Secondary outcomes Clinical response rate at TOC visit (25‐27 weeks after last dose) in people with osteomyelitis (sub study) Microbiologic response of eradication at TOC visit (after 12 days)
Notes	Funding source: sponsored by Pfizer Inc, 7 authors were employees of Pfizer Other: sample size calculation not reported; the sub study was underpowered
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated. participants stratified by the presence or absence of osteomyelitis and by infection severity (grade 2‐3 vs 4)
Allocation concealment (selection bias)	Low risk	Trans‐telephonic randomizations
Incomplete outcome data (attrition bias) All outcomes	Low risk	Not ITT analysis: 11 participants did not receive the study drug and were not considered in the analysis (MITT: Modified ITT) but there were no differences between groups Withdrawals were similar between groups and reasons reported
Selective reporting (reporting bias)	Low risk	Available protocol: NCT00366249. Same outcomes as those reported in the protocol
Other bias	Unclear risk	N/A
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blinded. Dose adjustment was done by an unblinded dispenser at the request of the investigator at the investigational site’s standard of care
Blinding of outcome assessment (detection bias) All outcomes	Low risk	A blinded investigator assessed the outcome