POISE‐2 2013.

Methods	Study design: parallel RCT Study duration: January 2011 to December 2013 Study follow‐up: 30 POD
Participants	Countries: Canada, USA, Colombia, India, Spain, Australia, South Africa, Denmark, Hong Kong, Belgium, Austria, Pakistan, Peru, Malaysia, Italy, Chile, Switzerland, France, UK, Brazil, New Zealand Setting: multicentre (88) Inclusion criteria: patients undergoing non‐cardiac surgery Number: treatment group 1 (3443); treatment group 2 (3453); control group 1 (3462); control group 2 (3452) Mean age ± SD (years): treatment group 1 (69.3 ± 9.9); treatment group 2 (69.1 ± 10.0); control group 1 (69.1 ± 10.0); control group 2 (69.2 ± 9.9) Sex (M/F): treatment group 1 (1808/1635);treatment group 2 (1846/1607); control group 1 (1861/1601); control group 2 (1823/1629) Exclusion criteria: ESKD prior to randomisation; no pre‐ or post‐randomisation SCr measurement available
Interventions	Treatment group 1 Aspirin: 200 mg 2 to 4 h before surgery and then 100 mg for either 7 days (for those taking long‐term aspirin) or 30 days (for those not taking long‐term aspirin) Treatment group 2 (not included in meta‐analyses) Oral clonidine: 0.2 mg 2 to 4 h before surgery and then a transdermal clonidine patch (which provided clonidine 0.2 mg/d) until 72 h after surgery Control group 1 Placebo: 2 to 4 h before surgery and then placebo for up to 30 days after surgery Control group 2 (not included in meta‐analyses) Placebo: 2 to 4 h before surgery and then a transdermal placebo patch until 72 h after surgery
Outcomes	AKI Dialysis within 30 days
Notes	Treatment group 2 and control group 2 not included in the meta‐analyses (wrong intervention) Funding source: funding received from the industry. Sponsors of the study had no role in the design and conduct of the study, data collection and analysis or publication. Financial support provided from Australian National Health and Medical Research Council, the Spanish Ministry of Health and Social Policy. Study drugs were provided by Boehringer Ingelheim and Bayer Pharma AG. Boehringer Ingelheim provided an uncertain amount of funding Up to 10% of patients included had an eGFR of 45 mL/min or less at start of the study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerized randomisation
Allocation concealment (selection bias)	Low risk	Concealed allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Patients, clinicians, data collectors, and outcome adjudicators were blinded to the allocation of each intervention.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Patients, clinicians, data collectors, and outcome adjudicators were blinded to the allocation of each intervention.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Less than 5% missing creatinine values were reported. Multiple imputation models were used to handle missing data, which all yielded similar results
Selective reporting (reporting bias)	Low risk	Study protocol matches outcomes presented
Other bias	Low risk	Contribution of funding sources unclear, however financial support provided by two large governmental non‐profit organisations. The authors state that the sponsors had no role in the design and conduct of the study, collection, management, analysis, review or approval of the manuscript; and decision to submit the manuscript for publication