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

• ClinicalTrials.gov Identifier: NCT02056353
• Recruitment Status: Completed
• First Posted: February 6, 2014
• Last Update Posted: January 8, 2016
• Sponsor: KU Leuven
• Collaborator: Agentschap voor Innovatie door Wetenschap en Technologie
• Information provided by (Responsible Party): Greet Van den Berghe, KU Leuven

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Critical Illness; Hyperglycemia; Hypoglycemia	Device: LOGIC-Insulin algorithm; Device: Paper protocol	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: LOGIC-Insulin Computerized Algorithm-guided Versus Nurse-directed Blood Glucose Control in Critically Ill Patients: the LOGIC-2 Multicentre Randomized Controlled Trial
• Study Start Date: February 2014
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Glycemic Penalty Index (GPI) during the Intervention [ Time Frame: up to 14 days post-randomization ]
   Adequacy of reaching and maintaining the target range for blood glucose during the intervention (Effectiveness of glycaemic control)

Secondary Outcome Measures :

1. Proportion of Patients With Severe Hypoglycaemia (<40 mg/dL) during the Intervention [ Time Frame: up to 14 days post-randomization ]
   Proportion of patients to have had one or more episodes of severe hypoglycaemia (<40 mg/dL) during the intervention
2. Incidence of Severe Hypoglycemia (<40 mg/dL) during the Intervention [ Time Frame: up to 14 days post-randomization ]
   Number of severe hypoglycaemic values as a fraction of all blood glucose measurements during the intervention
3. Blood Glucose Level Per Treatment Group during the Intervention [ Time Frame: up to 14 days post-randomization ]
   Mean and median arterial blood glucose level
4. Hyperglycaemic index (HGI) [ Time Frame: up to 14 days post-randomization ]
   Adequacy of reaching and maintaining the target range for blood glucose, as assessed by the Hyperglycaemic index (HGI)
5. Time in target range [ Time Frame: up to 14 days post-randomization ]
6. Time to target range [ Time Frame: up to 14 days post-randomization ]
7. Daily maximal blood glucose difference [ Time Frame: up to 14 days post-randomization ]
   marker of blood glucose fluctuations
8. Incidence of mild hypoglycaemia (blood glucose level < 70 mg/dL or 3.9 mmol/L) during the Intervention [ Time Frame: up to 14 days post-randomization ]
   Number of mild hypoglycaemic values as a fraction of all blood glucose measurements during the intervention
9. Proportion of Patients With Mild Hypoglycaemia (blood glucose level < 70 mg/dL or 3.9 mmol/L) during the Intervention [ Time Frame: up to 14 days post-randomization ]
   Proportion of patients to have had one or more episodes of mild hypoglycaemia during the intervention
10. Interval between blood glucose measurements [ Time Frame: up to 14 days post-randomization ]
    marker of workload
11. Protocol compliance in the intervention group [ Time Frame: up to 14 days post-randomization ]
    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.
12. Overrules in the intervention group [ Time Frame: up to 14 days post-randomization ]

    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
13. Incidence of new infections in the ICU [ Time Frame: up to 90 days post-randomization ]
    The diagnosis of "new infection" will be based on the administration of antibiotics, beyond the prophylactic scope
14. Length of stay in the ICU [ Time Frame: up to 90 days post-randomization ]
15. Length of stay in the hospital [ Time Frame: up to 90 days post-randomization ]
16. Mortality in the ICU [ Time Frame: up to 90 days post-randomization ]
17. Mortality in the hospital [ Time Frame: up to 90 days post-randomization ]
18. Landmark 90-day mortality [ Time Frame: up to 90 days post-randomization ]
19. All direct medical costs from a healthcare payer's perspective [ Time Frame: up to 90 days post-randomization ]
20. Quality of Life [ Time Frame: up to 90 days post-randomization ]
    EuroQol-5D

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Belgium

Jessa Hospital

Hasselt, Belgium, 3500

Dept Intensive Care Medicine, University Hospitals Leuven

Leuven, Belgium, 3000

Medical Intensive Care, University Hospitals Leuven

Leuven, Belgium, 3000

Netherlands

Academic Medical Center (AMC)

Amsterdam, Netherlands, 1105

Sponsors and Collaborators

KU Leuven

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)

More Information

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. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Greet Van den Berghe, Prof. Dr., KU Leuven
• ClinicalTrials.gov Identifier: NCT02056353
• 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 )
• First Posted: February 6, 2014
• Last Update Posted: January 8, 2016
• Last Verified: January 2016

Keywords provided by Greet Van den Berghe, KU Leuven:

Software; Algorithm; Cardiac surgery

Additional relevant MeSH terms:

Hypoglycemia; Hyperglycemia; Critical Illness; Glucose Metabolism Disorders; Metabolic Diseases; Disease Attributes; Pathologic Processes; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs