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

Not Applicable

Completed

Conditions: Critical Illness

Interventions: Procedure: LOGIC-Insulin
Procedure: Nurse directed

Registration Number: NCT01420302

Lead Sponsor: Greet Van den Berghe

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 300

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LOGIC-Insulin	LOGIC-Insulin	Blood glucose control (80-110 mg/dL) guided by the LOGIC-Insulin algorithm
Nurse-directed	Nurse directed	Nurse-directed blood glucose control (80-110 mg/dL)

Primary Outcome Measures

Name	Time	Method
Glycemic Penalty Index (GPI) During the Intervention	The GPI is the average of all penalties that are individually assigned to all blood glucose values obtained up to 14 days post-randomization, based on an optimized smooth penalty function.	The GPI is an index (ranging from 0 to 100) derived from the blood glucose values that are outside the target level of 80-110 mg/dL, in both the hyperglycemic and the hypoglycemic ranges. The weight of the penalty score of a blood glucose measurement is proportional to the level of deviation from normoglycemia. The GPI is the average of all penalties that are individually assigned to all blood glucose values, based on an optimized smooth penalty function. Higher GPI scores indicate lower efficacy of glycemic control.

Secondary Outcome Measures

Name	Time	Method
Incidence of Severe Hypoglycemia (<40 mg/dL) During the Intervention	up to 14 days post-randomization	Number of severe hypoglycemic values as a fraction of all blood glucose measurements during the intervention
Blood Glucose Level Per Treatment Group During the Intervention	up to 14 days post-randomization
Interval Between Blood Glucose Measurements During the Intervention	up to 14 days post-randomization	Marker of workload
Percentage of Time in Target Zone (80-110 mg/dL) During the Intervention	up to 14 days post-randomization	Adequacy of reaching and maintaining the target range for blood glucose during the intervention
Length of Stay in ICU	up to 90 days post-randomization
Length of Stay in Hospital	up to 90 days post-randomization
Incidence of Common Hypoglycemia (<60 mg/dL) During the Intervention	up to 14 days post-randomization	Number of common hypoglycemic values as a fraction of all blood glucose measurements during the intervention
Proportion of Patients With Severe Hypoglycemia (<40 mg/dL) During the Intervention	up to 14 days post-randomization	Proportion of patients to have had one or more episodes of severe hypoglycemia (\<40 mg/dL) during the intervention
Hospital Mortality	up to 90 days post-randomization	Patients who will have been discharged from hospital before 90 days post-randomization will be regarded as survivors
Hyperglycemic Index (HGI) During the Intervention	up to 14 days post-randomization	Adequacy of reaching and maintaining the target range for blood glucose during the intervention
Daily Maximal Blood Glucose Difference During the Intervention	up to 14 days post-randomization	Marker of blood glucose variability
Proportion of Patients With Common Hypoglycemia (<60 mg/dL) During the Intervention	up to 14 days post-randomization	Proportion of patients to have had one or more episodes of common hypoglycemia during the intervention