LOGIC-Insulin Algorithm-guided Versus Nurse-directed Blood Glucose Control During Critical Illness (LOGIC-1)

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

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

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Procedure: LOGIC-Insulin; Procedure: Nurse directed

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Dept Intensive Care Medicine, University Hospitals Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Penalty Index (GPI) During the Intervention	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.	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.

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

Collaborators and Investigators

• Sponsor: Greet Van den Berghe
• Collaborators: Fund for Scientific Research, Flanders, Belgium; Agency for Innovation by Science and Technology, Flanders, Belgium
• Investigators: Study Director: Dieter Mesotten, MD, PhD, KU Leuven; Principal Investigator: Greet Van den Berghe, MD, PhD, KU Leuven; Principal Investigator: Tom Van Herpe, Eng, PhD, KU Leuven; Principal Investigator: Bart De Moor, Eng, PhD, KU Leuven

Publications and helpful links

General Publications

• van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. doi: 10.1056/NEJMoa011300.
• Van Herpe T, De Brabanter J, Beullens M, De Moor B, Van den Berghe G. Glycemic penalty index for adequately assessing and comparing different blood glucose control algorithms. Crit Care. 2008;12(1):R24. doi: 10.1186/cc6800. Epub 2008 Feb 26.
• Van Herpe T, De Moor B, Van den Berghe G. Towards closed-loop glycaemic control. Best Pract Res Clin Anaesthesiol. 2009 Mar;23(1):69-80. doi: 10.1016/j.bpa.2008.07.003.
• Van Herpe T, Mesotten D, Wouters PJ, Herbots J, Voets E, Buyens J, De Moor B, Van den Berghe G. LOGIC-insulin algorithm-guided versus nurse-directed blood glucose control during critical illness: the LOGIC-1 single-center, randomized, controlled clinical trial. Diabetes Care. 2013 Feb;36(2):188-94. doi: 10.2337/dc12-0584. Epub 2012 Sep 6.

Helpful Links

• Leuven Laboratory Intensive Care Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: August 17, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimated): August 19, 2011

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: algorithm; intensive care; insulin; critical illness; glucose; blood glucose control
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: LOGIC-Insulin 1.1.1.; S 51956 (Other Identifier: University Hospitals Leuven); 80M0437 (Other Identifier: Belgian Federal Agency for Medicines and Health Products); ML 6079 (Other Identifier: IRB)