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

Intensive Care Med. 2021 Nov;47(11):1271-1283. doi: 10.1007/s00134-021-06526-8. Epub 2021 Sep 29.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose
  • Critical Illness*
  • Humans
  • Hyperglycemia* / drug therapy
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Intensive Care Units

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT02244073