Glucontrol 2009.

Study characteristics
Methods	Study design: parallel randomised controlled clinical trial with randomisation ratio of 1:1
Participants	Inclusion criteria: adult participants (older than 18 years) admitted to the participating ICUs Exclusion criteria: life expectancy lower than 24 hours, and the absence of consent Diagnostic criteria: — Setting: medical and surgical ICU Age group: adults Gender distribution: females and males Countries where trial was performed: Austria, Belgium, France, Israel, The Netherlands, Slovenia, Spain
Interventions	Intervention(s): intensive insulin therapy (4.4 mmol/L to 6.1 mmol/L) Comparator(s): intermediate target (7.8 mmol/L to 10.0 mmol/L) Duration of intervention: during ICU stay Duration of follow‐up: 28 days Run‐in period: none Number of study centres: 21 Treatment before trial: —
Outcomes	Reported outcome(s) in full text of publication: the primary outcome variable was the all‐cause absolute mortality during the ICU stay. Secondary outcome variables included hospital and 28‐day mortality, ICU and hospital, length of stay (LOS), incidence of organ failures assessed by the daily SOFA score, rate of hypoglycaemia and the SOFA score on the day of hypoglycaemia, duration of mechanical ventilation, inotrope/vasopressor and renal replacement therapy, number of packed red blood cells transfusion (PRBC), febrile days and days with therapeutic anti‐infective agents
Study registration	Trial identifier:NCT00107601 Trial terminated early: yes (due to a high rate of unintended protocol violations)
Publication details	Language of publication: English Funding: non‐commercial funding. Supported by a grant from the ‘Communauté Française Wallonie‐Bruxelles’ (Belgium) Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The present study was undertaken to test the hypothesis that IIT improves survival of patients treated in medico‐surgical intensive care units (ICU), as compared with a glucose control target of 7.8 ‐ 10.0 mmol/L, lower than in the Leuven trials [...] Specifically, this study was designed to detect whether IIT was associated with a 4% decrease of the absolute ICU mortality"
Notes	Information exclusively on diabetes participants was provided by trial authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The central computerised randomisation (blocks of eight patients) was stratified by centre and concealed"
Allocation concealment (selection bias)	Low risk	Quote: “The central computerised randomization (blocks of eight patients) was stratified by centre and concealed” Comment: probably adequate concealment
Blinding of participants and personnel (performance bias) All‐cause mortality	Low risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Hypoglycaemic episodes	High risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Adverse events other than hypoglycaemic episodes	High risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Cardiovascular events	Low risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Renal failure	Low risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure unlikely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Length of ICU and hospital stay	High risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure likely influenced by lack of blinding
Blinding of participants and personnel (performance bias) Mean blood glucose during intervention	High risk	Quote: “Inherently related to the intervention under investigation, the study was not blinded, ...”; outcome measure likely influenced by lack of blinding
Blinding of outcome assessment (detection bias) All‐cause mortality	Low risk	Quote: "The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Blinding of outcome assessment (detection bias) Hypoglycaemic episodes	Low risk	Quote: "The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Blinding of outcome assessment (detection bias) Adverse events other than hypoglycaemic episodes	Low risk	Quote: “The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Blinding of outcome assessment (detection bias) Cardiovascular events	Low risk	Quote: “The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Blinding of outcome assessment (detection bias) Renal failure	Low risk	Quote: “The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Blinding of outcome assessment (detection bias) Length of ICU and hospital stay	Low risk	Quote: “The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Blinding of outcome assessment (detection bias) Mean blood glucose during intervention	Low risk	Quote: “The central data manager and the statistician were blinded to treatment assignment"; “The assessment of outcome and the statistical analysis were performed blindly”
Incomplete outcome data (attrition bias) All‐cause mortality	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Incomplete outcome data (attrition bias) Hypoglycaemic episodes	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Incomplete outcome data (attrition bias) Adverse events other than hypoglycaemic episodes	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Incomplete outcome data (attrition bias) Cardiovascular events	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Incomplete outcome data (attrition bias) Renal failure	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Incomplete outcome data (attrition bias) Length of ICU and hospital stay	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Incomplete outcome data (attrition bias) Mean blood glucose during intervention	Unclear risk	Quote: “...the trial was stopped early due to a high rate of unintended protocol violations.” “Specifically, the proportion of BG values in the assigned range calculated from the BG readings available at the time of the interim analysis [...] were deemed as a high rate of unintended protocol violation rate” Comment: the researchers did not report a sample size calculation for this trial. The trial randomised 1101 participants
Selective reporting (reporting bias)	Low risk	Comment: all outcomes described in the methods are reported in the results. Study powered for the primary outcome. Outcomes in the publication same as in the protocol (NCT00107601)
Other bias	Low risk	Nothing detected