Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial
Julien Bohé, Hassane Abidi, Vincent Brunot, Amna Klich, Kada Klouche, Nicholas Sedillot, Xavier Tchenio, Jean-Pierre Quenot, Jean-Baptiste Roudaut, Nicolas Mottard, Fabrice Thiollière, Jean Dellamonica, Florent Wallet, Bertrand Souweine, Alexandre Lautrette, Jean-Charles Preiser, Jean-François Timsit, Charles-Hervé Vacheron, Ali Ait Hssain, Delphine Maucort-Boulch, CONTROLe INdividualisé de la Glycémie (CONTROLING) Study Group, Aurèle Buzancais, Anne Marie Dupuy, Rémi Bruyère, Henri de Montclos, Marion Provent, Jocelyne Drai, Joëlle Goudable, Anne Mialon, Bernard Allaouchiche, Arnaud Friggeri, Véréna Landel, Hélène Boyer, Hervé Hyvernat, Céline Caruba-Bafghi, Edouard Soum, Christophe Leroy, Laurence Roszyk, Pierre Eric Danin, Julio Badie, Stefan Georgiev, Martine Laplace, Richard Jospe, Jérôme Morel, Ali Mofredj, Abdelbaki Azaouzi, Jean-Paul Aubry, Abdelhamid Fatah, Stanislas Ledochowski, Sabine Zaepfel, Eric Fontaine, Julien Bohé, Hassane Abidi, Vincent Brunot, Amna Klich, Kada Klouche, Nicholas Sedillot, Xavier Tchenio, Jean-Pierre Quenot, Jean-Baptiste Roudaut, Nicolas Mottard, Fabrice Thiollière, Jean Dellamonica, Florent Wallet, Bertrand Souweine, Alexandre Lautrette, Jean-Charles Preiser, Jean-François Timsit, Charles-Hervé Vacheron, Ali Ait Hssain, Delphine Maucort-Boulch, CONTROLe INdividualisé de la Glycémie (CONTROLING) Study Group, Aurèle Buzancais, Anne Marie Dupuy, Rémi Bruyère, Henri de Montclos, Marion Provent, Jocelyne Drai, Joëlle Goudable, Anne Mialon, Bernard Allaouchiche, Arnaud Friggeri, Véréna Landel, Hélène Boyer, Hervé Hyvernat, Céline Caruba-Bafghi, Edouard Soum, Christophe Leroy, Laurence Roszyk, Pierre Eric Danin, Julio Badie, Stefan Georgiev, Martine Laplace, Richard Jospe, Jérôme Morel, Ali Mofredj, Abdelbaki Azaouzi, Jean-Paul Aubry, Abdelhamid Fatah, Stanislas Ledochowski, Sabine Zaepfel, Eric Fontaine
Abstract
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.
Trial registration: ClinicalTrials.gov NCT02244073.
Keywords: Glucose control; Glycated haemoglobin A1c; Hyperglycaemia; Individualised glucose control; Insulin.
Conflict of interest statement
We declare no competing interests.
© 2021. The Author(s).
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