NICE SUGAR 2009.
| Study characteristics | ||
| Methods | Study design: parallel randomised controlled clinical trial with randomisation ratio of 1:1 | |
| Participants |
Inclusion criteria: medical and surgical participants admitted to the ICU of 42 hospitals, expected to require treatment in the ICU on 3 or more consecutive days Exclusion criteria: imminent death, diabetic ketoacidosis or hyperosmolar state, in ICU for more than 24 hours, expected to be eating before 3rd day after admission, no informed consent, enrolled in the NICE‐SUGAR previously, suffered hypoglycaemia without full neurological recovery Diagnostic criteria for diabetes: on the basis of their medical history Setting: 38 academic tertiary care hospitals and 4 community hospitals Age group: adults Gender distribution: females and males Countries where trial was performed: Australia, New Zealand, Canada and USA |
|
| Interventions |
Intervention(s): intensive glucose control Comparator(s): conventional glucose control Duration of intervention: until participant was eating or discharged from ICU Duration of follow‐up: 90 days Run‐in period: none Number of study centres: 42 hospitals Treatment before trial (insulin): I: 29.8%, C: 27.3% |
|
| Outcomes | Reported outcome(s) in full text of publication: the primary outcome measure was death from any cause within 90 days after randomisation. Secondary outcome measures were survival time during the first 90 days, cause‐specific death and durations of mechanical ventilation, renal‐replacement therapy, and stays in the ICU and hospital. Tertiary outcomes were death from any cause within 28 days after randomisation, place of death (ICU, hospital ward or other), incidence of new organ failure, positive blood culture, receipt of red‐cell transfusion and volume of the transfusion | |
| Study registration |
Trial identifier:NCT00220987 Trial terminated early: no (certain participants yes) |
|
| Publication details |
Language of publication: English Funding: supported by grants from the Australian National Health and Medical Research Council, the Health Research Council of New Zealand, and the Canadian Institutes for Health Research. Dr. Finfer reports receiving reimbursement for travel to present research results at scientific meetings from Eli Lilly, Cardinal Health, and CSL Bioplasma and for serving on steering committees for studies sponsored by Eli Lilly and Eisai (paid to the George Institute for International Health); he also reports that the George Institute for International Health, an independent, not‐for‐profit institute affiliated with the University of Sydney, has received research funding from Servier, Novartis, Eisai, Merck Sharp & Dohme, Pfizer Australia, Fresenius Kabi Deutschland, and Sanofi‐Aventis Publication status: peer‐reviewed journal |
|
| Stated aim of study | Quote: "We designed the normoglycaemia in Intensive Care Evaluation‐Survival Using Glucose Algorithm Regulation (NICE‐SUGAR) trial to test the hypothesis that intensive glucose control reduces mortality at 90 days" | |
| 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: “Patients were randomly assigned to a treatment group by the clinicians treating them or by local study coordinators, with the use of a minimization algorithm” Quote: (from the protocol): “The George Institute for International Health will take responsibility for the web‐based randomisation. This will be available 24 hours a day.” |
| Allocation concealment (selection bias) | Low risk | Quote: “Patients were randomly assigned to a treatment group by the clinicians treating them or by local study coordinators, with the use of a minimization algorithm accessed through a secure Web site. The treatment assignments were concealed before randomization” |
| Blinding of participants and personnel (performance bias) All‐cause mortality | Low risk |
Quote: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” Comment: outcome measure unlikely influenced by lack of blinding |
| Blinding of participants and personnel (performance bias) Hypoglycaemic episodes | High risk |
Quote: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” 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: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” Comment: outcome measure likely influenced by lack of blinding |
| Blinding of participants and personnel (performance bias) Renal failure | Low risk |
Quote: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” 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: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” Comment: outcome measure likely influenced by lack of blinding |
| Blinding of participants and personnel (performance bias) Infection events | High risk |
Quote: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” Comment: outcome measure likely influenced by lack of blinding |
| Blinding of participants and personnel (performance bias) Mean blood glucose during intervention | High risk |
Quote: “The treatment assignments were concealed before randomization, but subsequently, clinical staff were aware of them” Comment: outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Infection events | High risk |
Quote “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) All‐cause mortality | Low risk |
Quote: “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure unlikely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Hypoglycaemic episodes | High risk |
Quote “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Adverse events other than hypoglycaemic episodes | High risk |
Quote “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Renal failure | Low risk |
Quote “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure unlikely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Length of ICU and hospital stay | High risk |
Quote “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure likely influenced by lack of blinding |
| Blinding of outcome assessment (detection bias) Mean blood glucose during intervention | High risk |
Quote “The primary outcome measure is mortality and therefore not subject to ascertainment bias” Comment: the trial report did not provide any detail on blinded assessment; outcome measure likely influenced by lack of blinding |
| Incomplete outcome data (attrition bias) All‐cause mortality | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Incomplete outcome data (attrition bias) Hypoglycaemic episodes | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Incomplete outcome data (attrition bias) Adverse events other than hypoglycaemic episodes | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Incomplete outcome data (attrition bias) Renal failure | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Incomplete outcome data (attrition bias) Length of ICU and hospital stay | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Incomplete outcome data (attrition bias) Infection events | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Incomplete outcome data (attrition bias) Mean blood glucose during intervention | Low risk | Comment: sample size calculation for 6100 participants. 6014 participants were randomised, but the treatment was discontinued in 10% of participants assigned to intensive glucose control and 7% of controls, with balanced reasons between groups |
| Selective reporting (reporting bias) | Low risk | Comment: study was powered for the primary outcome. All outcomes described in the methods and protocol (NCT00220987) are reported in the results |
| Other bias | Low risk | Nothing detected |