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

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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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Corresponding author

Correspondence to Jean-Charles Preiser.

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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

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