GLUCOSAFE 2 - A New Tool for Nutritional Management and Insulin-therapy in the Intensive Care Unit (ICU)

Study Overview
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Brief Summary
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The survival and the outcomes of critically ill patients are strongly influenced by insulin-therapy and nutritional support. The GLUCOSAFE 2 pilot study, aims to test the performance and the security of the new GLUCOSAFE 2 software, developed by the model-based medical decision support of Aalborg University (Denmark) and adapted to the clinical needs in the intensive care unit (ICU) of the Geneva University Hospital (HUG). This new device is based on a mathematical model of the glucose-insulin metabolism and attempts to give advices for better glycaemia control and nutritional therapy. The GLUCOSAFE 2 study hypothesizes that the use of the Glucosafe 2 software will allow better glycaemia (Time-in-target) control and better achievement of nutritional energy and protein targets in comparison to the local protocols.

Official Title
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GLUCOSAFE 2 - A New Tool for Nutritional Management and Insulin-therapy in the Intensive Care Unit (ICU): Randomized Controlled Study

Conditions
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Critical Illness, Energy Supply; Deficiency, Severe, Protein Deficiency, Hypoglycemia, Hyperglycemia

Intervention / Treatment
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* Device: GLUCOSAFE 2
* Device: Local protocol control group with routine care
* Device: Historical control group with routine care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients ≥ 18 years admitted to the ICU with An expected length of stay ≥ 72h At least 1 blood glucose (BG) measurement ≥10 mmol/l or 2 BG measurement ≥ 8.5 mmol/l Informed Consent signed by the subject/ legal representative, except for patients in the historical control group Exclusion Criteria: Lack of legal consent or consent withdrawn, except for patients in the historical control group Pregnant or breast feeding Diabetic ketoacidosis or hyperosmolar state Oral feeding Fulminant hepatic failure Medically contraindicated to receive rapidly acting insulin by intravenous (iv) infusion or iv injection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLUCOSAFE 2<br>Insulin-therapy and nutrition support guided by the GLUCOSAFE 2 software. | Device: GLUCOSAFE 2<br>* Use of GLUCOSAFE 2 software for nutrition management and insulin-therapy<br>|
| Active Comparator: Local protocol control group<br>Insulin-therapy and nutrition support guided by the local protocols (electronic or paper version) of the ICU/HUG. | Device: Local protocol control group with routine care<br>* Use of the local protocols (electronic or paper version) for nutrition management and blood glucose control.<br>|
| Other: Historical control group<br>Retrospective data with standard care before the beginning of the pilot study in order to minimize the cross-over effect due to the fact that caregivers are going to have in charge patients in both groups (intervention and control group) at the same time. | Device: Historical control group with routine care<br>* Use of the local protocols (electronic or paper version) for nutrition management and blood glucose control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-in-target (range: 5.0 - 8.5 mmol/l) | Time spent in the glycaemia range of 5.0 - 8.5 mmol/l per day, per patient and in the cohort | During ICU stay, up to 15 days post-randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall number of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events | Overall number of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events (per patient and in the cohort) | During ICU stay, up to 15 days post-randomization. | 
| Overall percentage of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events | Overall percentage of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events (per patient and in the cohort) | During ICU stay, up to 15 days post-randomization. | 
| Number of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events due to non-compliance | Overall number of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events due to non-compliance (only in intervention arm) | During ICU stay, up to 15 days post-randomization. | 
| Percentage of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events due to non-compliance | Percentage of mild (<3.3 mmol/l) and severe (<2.2 mmol/l) hypoglycemia events due to non-compliance (only in intervention arm) | During ICU stay, up to 15 days post-randomization. | 
| Time to normalize blood glucose (5.0-8.5 mmol/l) | Three values < 8.5 mmol/l as indicator for normalization | During ICU stay, up to 15 days post-randomization. | 
| Percentage of time in the ICU (per patient and in the cohort) with hyperglycaemia (BG > 8.5 mmol/l) | Percentage of time with BG > 8.5 mmol/l before and after normalization per patient and in the cohort. | During ICU stay, up to 15 days post-randomization. | 
| Percentage of time in the ICU (per patient and in the cohort) with hyperglycaemia (BG > 8.5 mmol/l) due to non compliance | Percentage of time with BG > 8.5 mmol/l before and after normalization per patient and in the cohort due to non compliance (only in the intervention arm). | During ICU stay, up to 15 days post-randomization. | 
| Number of hyperglycemic episodes after normalization (> 8.5 mmol/l) | Three values < 8.5 mmol/h as indicator for normalization | From normalization time during ICU stay, up to 15 days post-randomization. | 
| Number of hyperglycemic episodes after normalization (> 8.5 mmol/l) due to non compliance | Three values < 8.5 mmol/h as indicator for normalization | From normalization time during ICU stay, up to 15 days post-randomization. | 
| Number of episodes (per patient and in the cohort) where a BG measurements is not followed up within 30 minutes by a request for Glucosafe 2 advice | Number of episodes (per patient and in the cohort) where a BG measurements is not followed up within 30 minutes by a request for Glucosafe 2 advice | During ICU stay, up to 15 days post-randomization. | 
| Number of episodes (per patient and in the cohort) where pumps were not set within 30 min according to Glucosafe2 advice accepted by the nurse. | Number of episodes (per patient and in the cohort) when pumps were not set within 30 min according to Glucosafe2 advice accepted by the nurse. | During ICU stay, up to 15 days post-randomization. | 
| Number of advices given by GS2 which were accepted, accepted with modification, or rejected. | Number of advices given by GS2 which were accepted, accepted with modification, or rejected. | During ICU stay, up to 15 days post-randomization. | 
| Frequency of daily and cumulated BG measurements per patient and in the cohort | Frequency of BG measurements (per patient and in the cohort) | During ICU stay, up to 15 days post-randomization. | 
| Frequency of daily and cumulated adjustments of insulin and nutrition pump settings (per patient and in the cohort) | Frequency of daily and cumulated adjustments of insulin and nutrition pump settings (per patient and in the cohort) | During ICU stay, up to 15 days post-randomization. | 
| Glycaemic variability | Mean and standard deviation (SD) of blood glucose measurements. Daily maximum blood glucose difference. | During ICU stay, up to 15 days post-randomization. | 
| Protein goal achievements (80-100% of accumulated target) with a target of 1.3 g/kg of body weight per day. | Percentage of proteins received per day and at the end of the ICU stay with a target of 1.3 g/kg of body weight per day. | During ICU stay, up to 15 days post-randomization. | 
| Caloric goal achievements (80-100% of the accumulated target) by indirect calorimetry (IC) or predictive formula if IC not feasible. | Percentage of nutritional and non-nutritional calories received per day and at the end of the ICU stay with a target defined by IC or predictive formula if IC not feasible. | During ICU stay, up to 15 days post-randomization. | 
| Energy debt: difference between the defined energy target (80-100%, defined by IC or predictive formula) and the energy received (nutritional and non-nutritional) | Per day and at the end of the ICU stay. | During ICU stay, up to 15 days post-randomization. | 
| Protein debt: difference between the defined protein target (1.3 g/kg of body weight/day) and the proteins received | Per day and at the end of the ICU stay. | During ICU stay, up to 15 days post-randomization. | 
| Prediction of BG | Prediction error as a function of time elapsed since last BG measurement, per patient, per cohort.measurement (per patient and per cohort). | During ICU stay, up to 15 days post-randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin-therapy, ICU, Nutrition management, Glycaemia control, Software, Critical illness, Critically ill patients, Blood glucose control