A Multi-Center, Open Label Randomized Stratified Controlled Trial of the Effects of Blood Glucose Management on 90-Day All-Cause Mortality in a Heterogenous Population of Intensive Care Unit (ICU) Patients.
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- The George Institute
- Enrollment
- 6,104
- Locations
- 1
- Primary Endpoint
- all-cause mortality
Study Overview
Brief Summary
The primary aim of the study is to compare the effects of the two blood glucose targets on 90 day all-cause mortality in Intensive Care patients who are predicted on admission to stay in the ICU for at least one full calendar day. The hypothesis is that there is little difference in the relative risk of death between patients assigned a glucose range of 4.5 - 6.0 mmol/L, and those assigned a glucose range of less than 10.0 mmol/L with insulin being infused if blood glucose exceeds 10.0 mmol/L, and adjusted when needed to maintain blood glucose of 8.0 - 10.0 mmol/L.
Detailed Description
The NICE-SUGAR study is a multi-centre, open label, randomised controlled trial of blood glucose management with an intensive insulin regimen to maintain blood glucose between 4.5 - 6.0 mmol/L versus an insulin regimen maintaining blood glucose less than 10.0 mmol/L with insulin being infused if blood glucose exceeds 10.0 mmol/L, and adjusted when needed to maintain blood glucose between 8.0 - 10.0 mmol/L.
To ensure patient safety, the target blood glucose concentration must be closely monitored and the results known to the clinical staff treating the patients. As patient safety is paramount, it is not possible to blind the clinical staff to treatment allocation. In this open-label trial, bias will be minimised by ensuring concealment of treatment allocation prior to randomisation. The unblinded design risks introducing a systematic difference in some other treatment between the two groups, this is unlikely in the ICU setting where many other interventions will be administered simultaneously. The primary outcome measure is mortality and therefore not subject to ascertainment bias.
Patient recruitment
The treatment effect in Van den Berghe's study was limited to patients who stayed in Intensive Care for five days or longer, but all ventilated patients were admitted to the study at the time of ICU admission. Identifying patients who will stay in the ICU for five days or longer is problematic whereas it is relatively easy to identify patients, particularly patients admitted for routine post-operative monitoring, who will be discharged alive from the ICU after the day following admission. For that reason we propose to consider all patients but exclude those expected to be discharged alive or dead before the end of the day following admission.
The attending Intensive Care physician will make this assessment. In addition it is essential that patients who will stay in the ICU for greater than the eligible criteria time frame but who have a very low risk of death are excluded. For this reason we will exclude patients who are able to eat (or who are tube fed due to pre-existing bulbar or laryngeal dysfunction) and patients who do not merit an arterial line as part of their normal management.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients are eligible for INCLUSION in the study if ALL the following criteria are met:
- •At time of the patient's admission to the ICU the treating ICU specialist expects the patient will require treatment in the ICU that extends beyond the calendar day following the day of admission.
- •Patient has an arterial line in situ or placement of an arterial line is imminent (within the next hour) as part of routine ICU management.
Exclusion Criteria
- •Patients will be EXCLUDED from the study if ONE or MORE of the following criteria are present:
- •Age < 18 years.
- •Imminent death (cardiac standstill or brain death anticipated in less than 24 hours) and the treating clinicians are not committed to full supportive care. This should be confirmed by a documented treatment-limitation order that exceeds a "not-for-resuscitation" order.
- •Patients admitted to the ICU for treatment of diabetic ketoacidosis or hyperosmolar state.
- •Patient is expected to be eating before the end of the day following admission
- •Patients who have suffered hypoglycaemia without documented full neurological recovery.
- •Patient thought to be at abnormally high risk of suffering hypoglycaemia ( e.g. known insulin secreting tumour or history of unexplained or recurrent hypoglycaemia or fulminant hepatic failure)
- •If a patient has previously been enrolled in the NICE-SUGAR Study (patients cannot be enrolled in the NICE-SUGAR Study more than once).
- •If the patient can not provide prior informed consent, there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent
- •The patient has been in the study ICU or another ICU for longer than 24 hours for this admission.
- •There is no upper age limit for inclusion into the study unless any of the specific exclusion criteria are present.
Arms & Interventions
Intensive Insulin therapy
Intensive Insulin therapy
Intervention: Intensive Insulin Therapy (Other)
Conventional Therapy
conventional insulin therapy
Intervention: Conventional Insulin therapy (Other)
Outcomes
Primary Outcomes
all-cause mortality
Time Frame: 90 days
Secondary Outcomes
- The secondary outcomes, also determined over the same period of 90 days include:(90 days)
- All cause mortality(Day 28)
- Length of intensive care unit stay;(90 days)
- Length of hospital stay;(90 Days)
- The need for organ support (inotropes, renal replacement therapy and positive pressure ventilation);(90 Days)
- Incidence of blood stream infections;(90 Days)
- Incidence and severity of hypoglycaemia;(90 Days)
- extended glasgow outcome score(2 years)