Gandhi 2007.

Study characteristics
Methods	Study design: parallel randomised controlled clinical trial with randomisation ratio of 1:1
Participants	Inclusion criteria: adults undergoing elective cardiac surgery Exclusion criteria: participants who had off‐pump cardiopulmonary bypass procedures Diagnostic criteria: — Setting: St. Mary's Hospital Age group: adults Gender distribution: females and males Country where trial was performed: USA Co‐morbidities: chronic renal failure: I: 1%, C: 2%; history of myocardial infarction: I: 11%, C: 16%; stroke or transient ischaemic attack: I: 11%, C: 7%
Interventions	Intervention(s): intensive insulin therapy Comparator(s): conventional insulin therapy Duration of intervention: during the surgery Duration of follow‐up: 30 days Run‐in period: none Number of study centres: 1 Treatment before trial: Intervention: insulin 22%, oral diabetic medication 54%, both: 16% Comparator: insulin 28%, oral diabetic medication 31%, both: 19%
Outcomes	Reported outcome(s) in full text of publication: the primary outcome variable was a composite of death, sternal wound infections, prolonged pulmonary ventilation, cardiac arrhythmias (new‐onset atrial fibrillation, heart block requiring permanent pacemaker or cardiac arrest), stroke and acute renal failure within 30 days after surgery. Secondary outcome measures were length of stay in the ICU and hospital
Study registration	Trial identifier:NCT00282698 Trial terminated early: no
Publication details	Language of publication: English Funding: Novo Nordisk, Princeton, New Jersey, and Mayo Foundation and Mayo Clinic College of Medicine, Rochester, Minnesota funded the study Publication status: peer‐reviewed journal
Stated aim of study	Quote: "...we conducted a randomized, controlled trial at 1 center to determine whether maintenance of near normoglycaemia during cardiac surgery by using intraoperative intravenous insulin infusion reduced perioperative death and morbidity when added to rigorous postoperative glycaemic control "
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Randomization was computer generated with permuted blocks of 4, with stratification according to surgeon, surgical procedure (...), and diabetes”
Allocation concealment (selection bias)	Low risk	Quote: "The randomisation assignments were concealed in opaque, sealed, tamper‐proof envelopes that were opened sequentially by study personnel after participants signed the patient consent form"
Blinding of participants and personnel (performance bias) All‐cause mortality	Low risk	Comment: described as an open trial; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Hypoglycaemic episodes	High risk	Comment: described as an open trial; outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Adverse events other than hypoglycaemic episodes	High risk	Comment: described as an open trial; outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Cardiovascular events	Low risk	Comment: described as an open trial; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Renal failure	Low risk	Comment: described as an open trial; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Length of ICU and hospital stay	High risk	Comment: described as an open trial; outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Infection events	Low risk	Comment: described as an open trial; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Mean blood glucose during intervention	High risk	Comment: described as an open trial; outcome measure likely influenced by lack of blinding
Blinding of outcome assessment (detection bias) Infection events	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) All‐cause mortality	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) Hypoglycaemic episodes	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) Adverse events other than hypoglycaemic episodes	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) Cardiovascular events	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) Renal failure	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) Length of ICU and hospital stay	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Blinding of outcome assessment (detection bias) Mean blood glucose during intervention	Low risk	Quote: “Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis”
Incomplete outcome data (attrition bias) All‐cause mortality	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Hypoglycaemic episodes	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants participants randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Adverse events other than hypoglycaemic episodes	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Cardiovascular events	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Renal failure	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Length of ICU and hospital stay	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Infection events	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Incomplete outcome data (attrition bias) Mean blood glucose during intervention	Low risk	Comment: sample size calculation for 177 participants per treatment group that was adjusted to 200 participants to ensure a sufficient number of outcomes. 400 participants were randomised, with minimal dropouts that were balanced between groups
Selective reporting (reporting bias)	Low risk	Comment: all outcomes published in the protocol (NCT00282698) are reported in the publication. In the publication, primary outcomes from the protocol are considered a composite, and not all secondary outcomes described as secondary in the publication
Other bias	Low risk	Nothing detected