Multicentre LOGIC-Insulin Algorithm-guided Versus Nurse-directed Blood Glucose Control During Critical Illness (LOGIC-2) (LOGIC-2)

LOGIC-Insulin Computerized Algorithm-guided Versus Nurse-directed Blood Glucose Control in Critically Ill Patients: the LOGIC-2 Multicentre Randomized Controlled Trial

Most critically ill patients are confronted with hyperglycaemia, which is associated with an increased mortality and morbidity risk. Normalising these elevated blood glucose levels by intensive insulin therapy may improve patient outcome, but is associated with an increased risk of hypoglycaemia. The LOGIC-2 study hypothesises that the LOGIC-Insulin computerised software algorithm will allow better (less hyperglycaemia) and safer (less hypoglycaemia) blood glucose control in critically ill patients than nurse-directed blood glucose control.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Hypoglycemia; Critical Illness
• Intervention / Treatment: Device: Paper protocol; Device: LOGIC-Insulin algorithm

• Study Type: Interventional
• Enrollment (Actual): 1550
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium, 3500
    • Jessa Hospital
  • Leuven, Belgium, 3000
    • Dept Intensive Care Medicine, University Hospitals Leuven
  • Leuven, Belgium, 3000
    • Medical Intensive Care, University Hospitals Leuven
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Academic Medical Center (AMC)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients admitted to the ICU with an expected stay of at least 48 hours and already receiving or potentially needing insulin infusion for blood glucose control. These patients should already have or need an arterial and central venous line
• Patients should be 18 years or older

Exclusion Criteria:

• Not critically ill
• Age under 18 years
• Patients already enrolled in another intervention randomized controlled trial
• Patients expected to die within 12 hours (=moribund patients)
• No arterial line or central venous line needed
• Pregnancy or lactating
• Patients suffering from ketoacidotic or hyperosmolar coma on admission
• Patients who have been previously been included in the LOGIC-2 study
• Allergy to insulin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nurse-directed; Blood glucose control guided by paper protocol	Device: Paper protocol
Experimental: LOGIC-Insulin; Blood glucose control guided by the LOGIC-Insulin algorithm	Device: LOGIC-Insulin algorithm

What is the study measuring?

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 (Effectiveness of glycaemic control)	up to 14 days post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Severe Hypoglycaemia (<40 mg/dL) during the Intervention	Proportion of patients to have had one or more episodes of severe hypoglycaemia (<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 hypoglycaemic 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	Mean and median arterial blood glucose level	up to 14 days post-randomization
Hyperglycaemic index (HGI)	Adequacy of reaching and maintaining the target range for blood glucose, as assessed by the Hyperglycaemic index (HGI)	up to 14 days post-randomization
Time in target range		up to 14 days post-randomization
Time to target range		up to 14 days post-randomization
Daily maximal blood glucose difference	marker of blood glucose fluctuations	up to 14 days post-randomization
Incidence of mild hypoglycaemia (blood glucose level < 70 mg/dL or 3.9 mmol/L) during the Intervention	Number of mild hypoglycaemic values as a fraction of all blood glucose measurements during the intervention	up to 14 days post-randomization
Proportion of Patients With Mild Hypoglycaemia (blood glucose level < 70 mg/dL or 3.9 mmol/L) during the Intervention	Proportion of patients to have had one or more episodes of mild hypoglycaemia during the intervention	up to 14 days post-randomization
Interval between blood glucose measurements	marker of workload	up to 14 days post-randomization
Protocol compliance in the intervention group	the number and proportion of patients in which the LOGIC-Insulin was not followed for a time period of at least 8 hours, which is the duration of one nurse shift.	up to 14 days post-randomization
Overrules in the intervention group	the number and proportions of recommendations by the software that were overruled by the bed-side nurses; Minor overrules: absolute insulin dose difference of >0.1 and < 1IU/h; Major overrules: absolute insulin dose difference of >= 1IU/h; Major overrules will also be qualitatively assessed	up to 14 days post-randomization
Incidence of new infections in the ICU	The diagnosis of "new infection" will be based on the administration of antibiotics, beyond the prophylactic scope	up to 90 days post-randomization
Length of stay in the ICU		up to 90 days post-randomization
Length of stay in the hospital		up to 90 days post-randomization
Mortality in the ICU		up to 90 days post-randomization
Mortality in the hospital		up to 90 days post-randomization
Landmark 90-day mortality		up to 90 days post-randomization
All direct medical costs from a healthcare payer's perspective		up to 90 days post-randomization
Quality of Life	EuroQol-5D	up to 90 days post-randomization

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Agentschap voor Innovatie door Wetenschap en Technologie
• Investigators: Study Director: Dieter Mesotten, MD, PhD, KU Leuven; Principal Investigator: Greet Van den Berghe, MD, PhD, KU Leuven; Principal Investigator: Jasperina Dubois, MD, Jessa hospital, Hasselt; Principal Investigator: Marcus Schultz, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• 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.
• 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 den Berghe G, Schetz M, Vlasselaers D, Hermans G, Wilmer A, Bouillon R, Mesotten D. Clinical review: Intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target? J Clin Endocrinol Metab. 2009 Sep;94(9):3163-70. doi: 10.1210/jc.2009-0663. Epub 2009 Jun 16.
• Dubois J, Van Herpe T, van Hooijdonk RT, Wouters R, Coart D, Wouters P, Van Assche A, Veraghtert G, De Moor B, Wauters J, Wilmer A, Schultz MJ, Van den Berghe G, Mesotten D. Software-guided versus nurse-directed blood glucose control in critically ill patients: the LOGIC-2 multicenter randomized controlled clinical trial. Crit Care. 2017 Aug 14;21(1):212. doi: 10.1186/s13054-017-1799-6.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 6, 2014

Study Record Updates

• Last Update Posted (Estimate): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 7, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Cardiac surgery; Software; Algorithm
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease Attributes; Hyperglycemia; Hypoglycemia; Critical Illness; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: LOGIC-Insulin 2.1.1; ML9517 (Other Identifier: IRB-BE); S55613 (Other Identifier: University Hospitals Leuven); 80M0563 (Other Identifier: FAMHP); IWT-TBM 100793 (Other Grant/Funding Number: IWT-TBM)