Glucose Control in the ICU Using Continuous Glucose Monitoring (REGIMEN)

Randomized Evaluation of Glycaemic Control in the Medical Intensive Care Unit Using Continuous Glucose Monitoring (REGIMEN Trial)

Stress hyperglycemia occurs in 50-85% of patients admitted to a medical intensive care unit (MICU) and is associated with increased morbidity and mortality. However, randomized controlled trials examining the effects of strict glycemic control demonstrated conflicting results. A common finding in these trials was the high risk of hypoglycaemia.

This randomized controlled trial evaluates the impact of real-time continuous glucose monitoring (RT-CGM) on glycemic control and risk of hypoglycemia in severely ill MICU patients with an APACHE-II (Acute Physiology and Chronic Health Evaluation II) score ≥20.

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Device: experimental: real-time continuous glucose monitoring; Device: Active comparator: blinded continuous glucose monitoring

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • Middelheim General Hospital
  • Edegem, Belgium, 2650
    • Antwerp University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients admitted to a medical intensive care unit
• age: ≥ 18 y , < 75 y
• APACHE II (Acute Physiology and Chronic Health Evaluation II) score ≥ 20
• expected length of stay in ICU > 3 days

Exclusion Criteria:

• pregnancy
• patient with a DNR (do not reanimate) code
• surgical patient
• no informed consent

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
Experimental: real-time continuous glucose monitoring; real-time continuous glucose monitoring: Use will be made of the online real-time (RT) monitoring facility of the GlucoDay® (a continuous glucose monitoring (CGM)system). This will allow immediate adaptation of the insulin dose in order to maintain values within an optimal range. The same IV insulin infusion protocol will be used in the experimental and the active comparator group (adapted Yale protocol). When glycaemic changes of >25 mg/dl per 30 minutes are observed from the RT-CGM - GlucoDay data, this will be checked by measuring arterial blood glucose and the insulin infusion rate will be adapted according to the adapted Yale protocol.	Device: experimental: real-time continuous glucose monitoring; Other Names: RT-CGM using the GlucoDay device (A. Menarini, Italy)
Active Comparator: blinded continuous glucose monitoring; In the active comparator group the same continuous glucose monitoring device (GlucoDay) will be used in a blinded fashion. Glucose data will be analysed retrospectively. IV insulin infusion will be adapted according to arterial blood glucose values, using the adapted Yale protocol.	Device: Active comparator: blinded continuous glucose monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of time that patients are in target range of glycaemia (80-110 mg/dl)	after admission to the ICU, patients will be screened to check inclusion criteria, and CGM monitoring will commence within the first 48hrs after admission. CGM monitoring will be performed during 96 hours (4 days), during the first week after admission to the medical ICU	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of time that patients are in hypoglycaemic range	after admission to the ICU, patients will be screened to check inclusion criteria, and CGM monitoring will commence within the first 48hrs after admission. CGM monitoring will be performed during 96 hours (4 days), during the first week after admission to the medical ICU	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
accuracy of continuous glucose monitoring	error grid analysis, analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
glycaemic fluctuations	standard deviation of mean glucose value over 4 days, analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
accuracy of continuous glucose monitoring	Bland-Altman bias plot will be evaluated, analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
accuracy of continuous glucose monitoring	mean absolute error and mean relative error will be evaluated, analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
glycaemic fluctuations	MAGE (mean amplitude of glucose excursions), analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
glycaemic fluctuations	CONGA (continuous overlapping net glycemic action), analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
glycaemic fluctuations	area under curve (within target glycemia range, above target, below target) analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU
glycaemic fluctuations	MODD: mean of daily differences; analysing all data of the 4 days of continuous glucose monitoring period	participants will be followed for 96 hours (4 days), during the first week after admission to the medical ICU

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Christophe De Block, MD PhD, Antwerp University Hospital, Dept of Endocrinology, Diabetology & Metabolism

Publications and helpful links

General Publications

• De Block C, Manuel-Y-Keenoy B, Van Gaal L, Rogiers P. Intensive insulin therapy in the intensive care unit: assessment by continuous glucose monitoring. Diabetes Care. 2006 Aug;29(8):1750-6. doi: 10.2337/dc05-2353.
• De Block C, Manuel-y-Keenoy B, Rogiers P, Jorens P, Van Gaal L. Glucose control and use of continuous glucose monitoring in the intensive care unit: a critical review. Curr Diabetes Rev. 2008 Aug;4(3):234-44. doi: 10.2174/157339908785294460.
• Goldberg PA, Siegel MD, Sherwin RS, Halickman JI, Lee M, Bailey VA, Lee SL, Dziura JD, Inzucchi SE. Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care. 2004 Feb;27(2):461-7. doi: 10.2337/diacare.27.2.461.
• Shetty S, Inzucchi SE, Goldberg PA, Cooper D, Siegel MD, Honiden S. Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol. Endocr Pract. 2012 May-Jun;18(3):363-70. doi: 10.4158/EP11260.OR.
• Holzinger U, Warszawska J, Kitzberger R, Wewalka M, Miehsler W, Herkner H, Madl C. Real-time continuous glucose monitoring in critically ill patients: a prospective randomized trial. Diabetes Care. 2010 Mar;33(3):467-72. doi: 10.2337/dc09-1352. Epub 2009 Dec 10.
• De Block CE, Gios J, Verheyen N, Manuel-y-Keenoy B, Rogiers P, Jorens PG, Scuffi C, Van Gaal LF. Randomized Evaluation of Glycemic Control in the Medical Intensive Care Unit Using Real-Time Continuous Glucose Monitoring (REGIMEN Trial). Diabetes Technol Ther. 2015 Dec;17(12):889-98. doi: 10.1089/dia.2015.0151. Epub 2015 Aug 25.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: February 20, 2013
• First Submitted That Met QC Criteria: February 22, 2013
• First Posted (Estimate): February 26, 2013

Study Record Updates

• Last Update Posted (Estimate): February 26, 2013
• Last Update Submitted That Met QC Criteria: February 22, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: medical ICU patients; APACHE-II score ≥20
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: REGIMEN (Alias Study Number)