Insulin Glargine in the Intensive Care Unit: A Model-Based Clinical Trial Design

Type of content
Journal Article
Thesis discipline
Degree name
Publisher
University of Canterbury. Mechanical Engineering
Journal Title
Journal ISSN
Volume Title
Language
Date
2013
Authors
Willis, J.G.
Fisk, L.
Razak, N.
Le Compte, A.J.
Shaw, Geoff
Chase, Geoff
Abstract

Introduction: Current succesful AGC (Accurate Glycemic Control) protocols require extra clinical effort and are impractical in less acute wards where patients are still susceptible to stress-induced hyperglycemia. Long-acting insulin Glargine has the potential to be used in a low effort controller. However, potential variability in efficacy and length of action, prevent direct in-hospital use in an AGC framework for less acute wards. Method: Clinically validated virtual trials based on data from stable ICU patients from the SPRINT cohort who would be transferred to such an approach are used to develop a 24-hour AGC protocol robust to different Glargine potencies (1.0x, 1.5x and 2.0x regular insulin) and initial dose sizes (dose = total insulin over prior 12, 18 and 24 hours). Glycemic control in this period is provided only by varying nutritional inputs. Performance is assessed as %BG in the 4.0-8.0mmol/L band and safety by %BG<4.0mmol/L. Results: The final protocol consisted of Glargine bolus size equal to insulin over the previous 18 hours. Compared to SPRINT there was a 6.9% - 9.5% absolute decrease in mild hypoglycemia (%BG<4.0mmol/L) and up to a 6.2% increase in %BG between 4.0 and 8.0mmol/L. When the efficacy is known (1.5x assumed) there were reductions of: 27% BG measurements, 59% insulin boluses, 67% nutrition changes, and 6.3% absolute in mild hypoglycemia. Conclusion: A robust 24-48 clinical trial has been designed to safely investigate the efficacy and kinetics of Glargine as a first step towards developing a Glargine-based protocol for less acute wards. Ensuring robustness to variability in Glargine efficacy significantly affects the performance and safety that can be obtained.

Description
Online 4 Oct 2012
Citation
Willis, J.G., Fisk, L., Razak, N., Le Compte, A.J., Shaw, G.M., Chase, J.G. (2013) Insulin Glargine in the Intensive Care Unit: A Model-Based Clinical Trial Design. Biomedical Signal Processing & Control (BSPC), 8(2), pp. 120-129.
Keywords
clinical trial, simulation, glycemic control
Ngā upoko tukutuku/Māori subject headings
ANZSRC fields of research
Fields of Research::32 - Biomedical and clinical sciences::3202 - Clinical sciences::320208 - Endocrinology
Fields of Research::32 - Biomedical and clinical sciences::3202 - Clinical sciences::320212 - Intensive care
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