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).
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Acknowledgments
Supported by a grant from the ‘Communauté Française Wallonie-Bruxelles’ (Belgium).
We are indebted to Dr Daniel De Backer (Erasme University Hospital Brussels, Belgium), Dr Mette Berger (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) and Prof. Pedro Saavedra (University of Las Palmas de Gran Canaria, Spain).
The members of the independent Data and Safety monitoring board were Christian Mélot, Peter Radermacher and Greet Van den Berghe.
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Appendix 1: list of participants
Appendix 1: list of participants
Austria
University Clinic of Innsbruck
(M Joannidis)
13 patients
Belgium
Regional Centre Hospital of Citadelle, Liege (F Damas, V Fraipont)
40 patients
University Hospital Centre, Liege (JL Canivet, P Damas, B Lambermont, D Ledoux)
4 units: 141 + 158 + 16 + 110 patients
France
Raymond Poincaré Hospital, Garches (D Annane)
74 patients
Gustave-Roussy Institute, Villejuif (G Nitenberg)
12 patients
Israel
Rabin Medical Centre, Petah Tiqva (P Singer)
85 patients
The Netherlands
Free University Medical Centre, Amsterdam (J Groeneveld)
10 patients
Slovenia
University Medical Centre, Ljubljana (A Stecher, L Kompan)
112 patients
Spain
University General Hospital, Alicante (J Acosta Escribano, S Almanza; R Carrasco Moreno, M Fernández Vivas, V Ortolá Vercher)
15 patients
University Hospital Germans Trias i Pujol, Badalona (ML Bordejé, P Marcos Neira, S Martínez Vega, H Pérez Moltó)
53 patients
Dr Josep Trueta University Hospital, Girona (A Bonet Sarís, N López de Arbina, P Ortiz Ballugera)
28 patients
Dr. Negrín University Hospital, Las Palmas de Gran Canaria (S Ruiz-Santana, P Saavedra, Hípola Escalada, MA Hernández Viera, R Manzanedo Velasco, JJ Díaz Díaz)
101 patients
Hospital Severo Ochoa, Leganés (J López Martinez, R Díaz Abad)
35 patients
University Hospital 12 October, Madrid (JC Montejo, T Grau Carmona, C García Fuentes)
2 units: 15 + 40 patients
Provincial Hospital of Toledo (B García Vila, ML Rodríguez Blanco, MC Martín Parra)
19 patients
Dr Peset Hospital, Valencia (M Cervera Montes, C Campos, A Castillo, S Sancho, JM Simón)
24 patients
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Preiser, JC., Devos, P., Ruiz-Santana, S. et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 35, 1738–1748 (2009). https://doi.org/10.1007/s00134-009-1585-2
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DOI: https://doi.org/10.1007/s00134-009-1585-2