LOGIC-Insulin Algorithm-guided Versus Nurse-directed Blood Glucose Control During Critical Illness

Study Overview
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Brief Summary
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The LOGIC-Insulin computerized software algorithm will be compared with a nurse-directed protocol, both targeting a blood glucose level of 80-110 mg/dL, in critically ill patients

Detailed Description
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Critical illness typically causes elevated blood glucose concentrations, which have been associated with increased mortality. Strictly normalizing these blood glucose levels by intensive insulin therapy, called tight glycemic control, decreased morbidity and mortality in well-controlled single-center clinical studies. However, multi-center pragmatic trials failed to reproduce those effects, proving that the implementation of tight glycemic control in daily clinical practice is rather difficult. A computerized algorithm, amongst others, may help the nurses in the titration of insulin to reach normal blood glucose levels and to avoid the particularly worrisome hypoglycemia. The LOGIC-1 study is a single blinded randomized controlled trial. On admission patients will be randomly assigned to either tight glycemic control (80-110 mg/dL) by the computerized LOGIC-Insulin 3.0 algorithm or to tight glycemic control (80-110 mg/dL) by the nurse-directed protocol. Written informed consent will be asked from the patient in the case of elective surgery requiring post-operative ICU-admission. Proxy informed consent from the closest family member will be asked when the patient was admitted to the ICU in emergency. As blood glucose control by itself is essential in the management of critical illness, random allocation will be done on admission and written informed consent from the closest family member can be deferred to a maximum of 24 hours after randomization. The patient or family member can at all times withdraw from the trial without impact on his treatment. Allocation will be done in blocks (block size is unknown to the care givers responsible for treatment allocation), stratified into cardiac surgery and other reasons for ICU admission, by central computer randomization. The time window for the study will be 14 days starting from admission to the ICU or when one of the following stop criteria will be met: Withdrawal of the informed consent Patient starts eating or drinking sugar containing liquids Patient is discharged from the ICU (including ICU deaths) Removal of arterial line or central venous line Under the following conditions the study investigator/treating physician will be contacted and, if necessary, patients will be switched from LOGIC-Insulin to nurse-directed blood glucose control: Recurrent severe hypoglycemia (<40 mg/dL) Refractory hyperglycemia Any change in condition that compromises the safety of the patient, as judged by the investigator or treating physician The common strategy for blood glucose control in both groups involves blood glucose measurements from arterial blood by a blood gas analyzer and the administration of insulin through a central line with a syringe pump.

Official Title
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LOGIC-Insulin Computerized Algorithm-guided Versus Nurse-directed Blood Glucose Control in Critically Ill Patients: the LOGIC-1 Randomized Controlled Trial

Conditions
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Critical Illness

Intervention / Treatment
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* Procedure: Nurse directed insulin titration
* Procedure: LOGIC-Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or more Admitted to the ICU Already receiving or needing insulin infusion for blood glucose control Exclusion Criteria: Not critically ill (eating, not mechanically ventilated) Pregnant or breastfeeding Previous inclusion into the trial Included in other trial Moribund Diabetes coma No arterial line available

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LOGIC-Insulin<br>Blood glucose control (80-110 mg/dL) guided by the LOGIC-Insulin algorithm | Procedure: LOGIC-Insulin<br>* Blood glucose control (80-110 mg/dL) guided by the LOGIC-Insulin algorithm<br>* Other names: software guided TGC;|
| Active Comparator: Nurse-directed<br>Nurse-directed blood glucose control (80-110 mg/dL) | Procedure: Nurse directed insulin titration<br>* Nurse directed insulin titration to establish glycemic control in the target range of 80-110 mg/dL<br>* Other names: Active comparator: titration-guidelines supported TGC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Penalty Index (GPI) during the intervention | Adequacy of reaching and maintaining the target range for blood glucose during the intervention | up to 14 days post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with severe hypoglycemia (<40 mg/dL) during the intervention | Proportion of patients to have had one or more episodes of severe hypoglycemia (<40 mg/dL) during the intervention | up to 14 days post-randomization | 
| Incidence of severe hypoglycemia (<40 mg/dL) during the intervention | Number of severe hypoglycemic values as a fraction of all blood glucose measurements during the intervention | up to 14 days post-randomization | 
| Blood glucose level per treatment group during the intervention |  | up to 14 days post-randomization | 
| Hyperglycemic index (HGI) during the intervention | Adequacy of reaching and maintaining the target range for blood glucose during the intervention | up to 14 days post-randomization | 
| Daily maximal blood glucose difference during the intervention | Marker of blood glucose variability | up to 14 days post-randomization | 
| Proportion of patients with common hypoglycemia (<60 mg/dL) during the intervention | Proportion of patients to have had one or more episodes of common hypoglycemia during the intervention | up to 14 days post-randomization | 
| Interval between blood glucose measurements during the intervention | Marker of workload | up to 14 days post-randomization | 
| Percentage of time in target zone (80-110 mg/dL) during the intervention | Adequacy of reaching and maintaining the target range for blood glucose during the intervention | up to 14 days post-randomization | 
| Length of stay in ICU |  | up to 90 days post-randomization | 
| Length of stay in hospital |  | up to 90 days post-randomization | 
| Hospital mortality | Patients who will have been discharged from hospital before 90 days post-randomization will be regarded as survivors | up to 90 days post-randomization | 
| Incidence of common hypoglycemia (<60 mg/dL) during the intervention | Number of common hypoglycemic values as a fraction of all blood glucose measurements during the intervention | up to 14 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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critical illness, intensive care, insulin, glucose, algorithm, blood glucose control