A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study

Byline: Jean-Charles Preiser (1,14), Philippe Devos (1), Sergio Ruiz-Santana (2), Christian Melot (3), Djillali Annane (4), Johan Groeneveld (5), Gaetano Iapichino (6), Xavier Leverve (7), Gerard Nitenberg (8), Pierre Singer (9), Jan Wernerman (10), Michael Joannidis (11), Adela Stecher (12), Rene Chiolero (13) Keywords: Insulin therapy; Insulin resistance; Stress hyperglycaemia; Hypoglycaemia; Critical illness Abstract: Purpose An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control. Methods Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8--10.0 mmol/L) or to group 2 (target BG 4.4--6.1 mmol/L). Results While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1--9.0) (median of all values) and 7.7 mmol/L (IQR 6.7--8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0--7.2) and 6.1 mmol/L (IQR 5.5--6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5--50.0) and 39.3 (26.2--53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%). Conclusions In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4--6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8--10.0 mmol/L target. (ClinicalTrials.gov NCT00107601, EUDRA-CT Number: 200400391440). Author Affiliation: (1) Department of General Intensive Care, University Hospital, Liege, Belgium (2) Department of Intensive Care, Dr Negrin University Hospital, University of Las Palmas de Gran Canaria, Las Palmas, Spain (3) Department of Intensive Care, Erasme Hospital, Brussels, Belgium (4) Department of Intensive Care, Raymond Poincare Hospital, Garches, France (5) Department of Intensive Care, Free University Medical Centre, Amsterdam, The Netherlands (6) Department of Anaesthesia and Intensive Care, Hospital of San Paolo, University of Milano, Milan, Italy (7) Department of Emergency and Intensive Care, Joseph Fourier University, Grenoble, France (8) Department of Intensive Care, Gustave-Roussy Institute, Villejuif, France (9) Department of Intensive Care, Rabin Medical Centre, Petah Tiqva, Israel (10) Department of Anaesthesia and Intensive Care, Karolinska Institute, Stockholm, Sweden (11) Department of Intensive Care, University Clinic Innsbruck, Innsbruck, Austria (12) Department of Anaesthesia and Intensive Care, University Medical Centre, Ljubljana, Slovenia (13) Department of Intensive Care, University Hospital Lausanne, Lausanne, Switzerland (14) Department of General Intensive Care, University Hospital of Liege, University of Liege, Domaine Universitaire du Sart-Tilman, 4000, Liege, Belgium Article History: Registration Date: 14/07/2009 Received Date: 10/11/2008 Accepted Date: 08/07/2009 Online Date: 28/07/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1585-2) contains supplementary material, which is available to authorized users.