Lazar 2011.

Study characteristics
Methods	Study design: parallel randomised controlled clinical trial with randomisation ratio of 1:1
Participants	Inclusion criteria: participants with diabetes mellitus undergoing CABG surgery on cardiopulmonary bypass Exclusion criteria: severe hyperglycaemia (serum glucose > 400 mg/dL), which could not be controlled on a stable insulin regimen preoperatively, chronic renal failure (creatinine level ≥ 2.5 mg/dL), acute renal failure (urine output < 20 mL/hour for 3 hours), and those participants requiring concomitant procedures in addition to CABG surgery Diagnostic criteria: — Setting: Boston Medical Center Age group: adults Gender distribution: females and males Country where trial was performed: USA Co‐morbidities: angina class IV: I: 33%, C: 33%; CHF: I: 13%, C: 14%; MI: I: 57%; C: 57%; HTN: I: 93%, C: 100%; left main disease: I: 15%; C: 21% Co‐medications: cardioprotective medication (β‐blockers, statins, ACE inhibitors)
Interventions	Intervention(s): aggressive group (serum glucose 90 mg/dL to 120 mg/dL) Comparator(s): moderate group (serum glucose 120 mg/dL to 180 mg/dL) Duration of intervention: during surgery and the next 18 hours in the ICU Duration of follow‐up: 30 days Run‐in period: none Number of study centres: 1 Treatment before trial: Intervention: β‐blockers: 100%; statins: 100%; ACE inhibitors: 60%; hyperlipidaemia treatment: 100%; insulin: 38%; oral diabetic agents: 52%, diet control: 5%; insulin and oral diabetic agents: 5% Comparator: β‐blockers: 100%; statins: 100%; ACE inhibitors: 59%; hyperlipidaemia treatment: 100%; insulin: 31%; oral diabetic agents: 48%, diet control: 10%; insulin and oral diabetic agents: 11%
Outcomes	Reported outcome(s) in full text of publication: to determine whether more aggressive glycaemic control would result in more optimal clinical outcomes and less morbidity than can be achieved with moderate control in participants with diabetes mellitus undergoing CABG surgery
Study registration	Trial identifier:NCT00460499 Trial terminated early: no
Publication details	Language of publication: English Funding: — Publication status: peer‐reviewed journal
Stated aim of study	Quote: "This study sought to determine whether aggressive glycaemic control (90 ‐ 120 mg/dL) would result in more optimal clinical outcomes and less morbidity than moderate glycaemic control (120 ‐ 180 mg/dL) in diabetic patients undergoing coronary artery bypass graft (CABG) surgery"
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "This was a prospective, randomized single center trial..." Comment: no additional details provided on randomisation sequence generation
Allocation concealment (selection bias)	Unclear risk	Quote: “This was a prospective, randomized single center trial …” Comment: no additional details provided on randomisation sequence concealment
Blinding of participants and personnel (performance bias) All‐cause mortality	Low risk	Quote: “Clinicians were not blinded to the treatment groups, ...” Comment: outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Hypoglycaemic episodes	High risk	Quote: “Clinicians were not blinded to the treatment groups, ...” Comment: outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Adverse events other than hypoglycaemic episodes	High risk	Quote: “Clinicians were not blinded to the treatment groups, ...” Comment: outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Cardiovascular events	Low risk	Quote: “Clinicians were not blinded to the treatment groups, ...” Comment: outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Renal failure	Low risk	Quote: “Clinicians were not blinded to the treatment groups, ...”. Comment: outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Length of ICU and hospital stay	High risk	Quote: “Clinicians were not blinded to the treatment groups, ...”. Comment: outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Infection events	High risk	Quote: “Clinicians were not blinded to the treatment groups, ...” Comment: outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Mean blood glucose during intervention	High risk	Quote: “Clinicians were not blinded to the treatment groups, ...” Comment: outcome measure likely influenced by lack of blinding
Blinding of outcome assessment (detection bias) Infection events	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) All‐cause mortality	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) Hypoglycaemic episodes	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) Adverse events other than hypoglycaemic episodes	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) Cardiovascular events	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) Renal failure	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) Length of ICU and hospital stay	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Blinding of outcome assessment (detection bias) Mean blood glucose during intervention	Low risk	Comment: the trial report did not provide any detail on blinded assessment, but the trial registration record disclosed that outcome assessment was masked
Incomplete outcome data (attrition bias) All‐cause mortality	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Incomplete outcome data (attrition bias) Hypoglycaemic episodes	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Incomplete outcome data (attrition bias) Adverse events other than hypoglycaemic episodes	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Incomplete outcome data (attrition bias) Cardiovascular events	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Incomplete outcome data (attrition bias) Renal failure	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Incomplete outcome data (attrition bias) Length of ICU and hospital stay	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Incomplete outcome data (attrition bias) Mean blood glucose during intervention	Low risk	Quote: “All patients completed the protocol, and none were lost to follow‐up.” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 82 participants
Selective reporting (reporting bias)	Unclear risk	Comment: one of the primary outcomes reported in the trial publication (incidence of major adverse events) was not disclosed at its trial register record
Other bias	Unclear risk	Quote: "Supported by a research grant by Eli Lilly..." Comment: Eli Lilly is a manufacturer of insulin. Also in the protocol an estimated enrolment of 400 is reported, however the study only enrolled 82 participants