Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial.

Julien Bohé (1, 2) , Hassane Abidi (1, 2) , Vincent Brunot (3) , Amna Klich (2, 4) , Kada Klouche (5, 6) , Nicholas Sedillot (7) , Xavier Tchenio (7) , Jean-Pierre Quenot (8, 9, 10, 11, 12) , Jean-Baptiste Roudaut (8) , Nicolas Mottard (1, 2) , Fabrice Thiollière (1, 2) , Jean Dellamonica (13, 14) , Florent Wallet (1, 2) , Bertrand Souweine (15, 16) , Alexandre Lautrette (15, 16) , Jean-Charles Preiser (17) , Jean-François Timsit (18, 19) , Charles-Hervé Vacheron (1, 2) , Ali Ait Hssain (15) , Delphine Maucort-Boulch (2, 4, 20)

1 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
2 HCL - Hospices Civils de Lyon
3 CHU Montpellier
4 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
5 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
6 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
7 CHBBF - Centre Hospitalier Fleyriat [Bourg en Bresse]
8 CHU Dijon
9 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
10 LabEx LipSTIC - Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer
11 FCS Bourgogne Franche-Comté - Fondation de Coopération Scientifique Bourgogne Franche-Comté
12 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques
13 Hôpital l'Archet
14 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
15 CHU Gabriel Montpied [Clermont-Ferrand]
16 LMGE - Laboratoire Microorganismes : Génome et Environnement
17 ULB - Université libre de Bruxelles
18 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
19 UPD7 - Université Paris Diderot - Paris 7
20 Service de Biostatistiques [Lyon]

Purpose: Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient's pre-admission usual glycaemia, could improve outcome.Methods: In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days.Results: Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018).Conclusion: Targeting an ICU patient's pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.

Mots clés: Glucose control; Glycated haemoglobin A1c; Hyperglycaemia; Individualised glucose control; Insulin

Domaines: Sciences du Vivant [q-bio]

Julien Bohé, Hassane Abidi, Vincent Brunot, Amna Klich, Kada Klouche, et al.. Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial.. Intensive Care Medicine, 2021, ⟨10.1007/s00134-021-06526-8⟩. ⟨hal-03363013⟩