LOGIC-insulin - Clinical validation and filing for regulatory approval of a blood glucose regulator for the Intensive Care Unit

From 01-01-2011 to 31-12-2012

Description

Critically ill patients, admitted to the Intensive Care Unit  after e.g. major trauma,cardiac surgery, transplantation or severe infections are in an imminent life-threatening condition. Criticalillness typically leads to an increase of the blood glucose concentrations: the so-called stresshyperglycaemia. While stress hyperglycaemia has traditionally been regarded as an adaptive, beneficialresponse, it has also been clear from observational studies that hyperglycaemia, as well ashypoglycaemia, are associated with increased risk of death in critically ill patients. The associationbetween blood glucose levels and mortality risk follows a J-curved relationship with the nadir roughlybetween 80-140 mg/dL . The first randomized controlled trial (RCT) that showed hyperglycaemiaactively contributes to worsened patient outcome was performed in Leuven. This study targeted a “strictlynormal level for fasting blood glucose”, i.e. 80-110 mg/dL versus treating hyperglycaemia only when itexceeded the renal threshold of 215 mg/dL. The insulin dose-adaptations were based on a guideline tostimulate intuitive and anticipating decision making by bedside nurses. At the same time the study wasset up with a single-centre, proof-of-concept design. The latter encompassed precise arterial bloodglucose measurements with a blood gas analyser and the administration of insulin via an accuratesyringe pump and a homogeneous patient population (mainly cardiac surgery and high risk/complicatednon-cardiac surgery). The study showed that maintaining strict normoglycaemia by “intensive insulintherapy” lowered ICU mortality from 8.0% to 4.6%and in-hospital mortality from 10.9% to 7.2%.Further, ICU morbidity was reduced by preventingorgan failure (reflected in a shorter duration ofmechanical ventilation, a decreased incidence ofacute kidney failure, severe infections andpolyneuropathy and less blood transfusions).Generalising to the medical and paediatric critically illpatient population, these results were confirmed inthe same context of a well controlled, single-centreexpert setting.

Team

• Greta Van den Berghe, Co-promoter (External)
• Bart De Moor, Co-promoter
• Dieter Mesotten, Promoter (External)
• Tom Van Herpe, Team member

Financing

Funding: KU Leuven - Internal Funding KU Leuven

Program/Grant Type: IOF - IOF-mandaten: Postdoctoral Fellowships