Individualized Blood Glucose Control in ICU. The CONTROLING Study. A Double Blinded Multicentric Randomized Study. (CONTROLING)

Individualized Blood Glucose Control in ICU.

During the last 2 decades, the management of hyperglycemia in critically ill patients has become one of the most discussed topics in the intensive-care field. The initial data suggesting significant benefit from the normalization of blood glucose levels in critically ill patients using intensive intravenous insulin therapy (Van den Berghe G et al. N Engl J Med. 2001) has been tempered by later studies (Finfer S et al. N Engl J Med. 2009). Some studies suggested that strict blood glucose control might benefit in non-diabetic patient and worsen outcomes in diabetics. We hypothesized that an individualized blood glucose target based on glycated hemoglobin measured at ICU admission would improve outcome when compared to a standard care of maintaining blood glucose bellow 10 mmol/l (180 mg/dl). We designed a randomized double blinded study in which Blood glucose control is piloted in both groups by a web-guided protocol that directly gives instruction to nurses (https://extranet.chu-lyon.fr/cpg). The study will enroll 4200 patients in 10 centers. Primary end point is 90 d outcome after randomization.

Study Overview

• Status: Terminated
• Conditions: Critical Illness
• Intervention / Treatment: Drug: Human insulin - Insulin administration to control blood glucose level.

• Study Type: Interventional
• Enrollment (Actual): 2069
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Belfort, France
    • Hopital Nord Franche Comte
  • Bourg-en-Bresse, France, 01012
    • CH de BOURG-EN-BRESSE
  • Bourgoin Jallieu, France, 38302
    • Centre Hospitalier de Bourgoin-Jallieu
  • Chartres, France
    • CH Chartres
  • Clermont Ferrand, France, 63003
    • CHU de Clermont Ferrand - Gabriel Montpied
  • Dijon, France, 21079
    • CHU de Dijon - Complexe Hospitalier du Bocage
  • Montpellier, France, 34295
    • CHU de Montpellier - Hôpital Lapeyronie
  • Nice, France, 06202
    • CHU de Nice - Hôpital de l'Archet 1
  • Papeete, France
    • CH de Polynésie Française
  • Pierre Benite, France, 69310
    • Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
  • Salon de Provence, France, 13658
    • Centre Hospitalier de Salon de Provence
  • St Priest en Jarez, France, 42277
    • CHU de Saint Etienne - Hopital Nord

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients are eligible for INCLUSION in the study if ALL the following criteria are met:

• Patient is 18 year old or older;
• At time of the patient's admission to the ICU the treating ICU specialist expects the patient will require treatment in the ICU that extends beyond the calendar day following the day of admission.

Exclusion Criteria:

• Patients will be EXCLUDED from the study if ONE or MORE of the following criteria are present:

  • Patient or legal surrogate decision maker does not accept the participation to the study;
  • Imminent death (anticipated in less than 48 hours);
  • The treating clinicians are not committed to full supportive care (no resuscitation, no renal replacement therapy limits in dose of vasoactive support);
  • Patient is expected to be eating before the end of the day following admission;
  • Admission in ICU for hypoglycemic encephalopathy or patient at risk for hypoglycaemia ( e.g. known insulin secreting tumour or history of unexplained or recurrent hypoglycaemia or fulminant hepatic failure);
  • If a patient has previously been enrolled in the CONTROLING Study (patients cannot be enrolled in the CONTROLING Study more than once).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individualized blood glucose target; Maintain blood glucose in individualized target based on glycated hemoglobin level (A1c); Blood glucose level is maintained bellow 1.59 × A1c - 1.59 (mmol/l).	Drug: Human insulin - Insulin administration to control blood glucose level.; On ICU admission, the glycated hemoglobin level (A1c) is measured and insulin IV is possibly administered using a web based nurse driven insulin infusion protocol (https://extranet.chu-lyon.fr/cpg) to maintain blood glucose level below 10 mmol/l. Glycated hemoglobin result triggers patient randomization. Thereafter, during ICU stay, blood glucose level is maintained either below 1.59 × A1c - 1.59 (mmol/l) (Individualized blood glucose target group), or bellow 10 mmol/l (Conventional blood glucose target group).
Active Comparator: Conventional blood glucose target; Maintain blood glucose bellow 10 mmol/l.	Drug: Human insulin - Insulin administration to control blood glucose level.; On ICU admission, the glycated hemoglobin level (A1c) is measured and insulin IV is possibly administered using a web based nurse driven insulin infusion protocol (https://extranet.chu-lyon.fr/cpg) to maintain blood glucose level below 10 mmol/l. Glycated hemoglobin result triggers patient randomization. Thereafter, during ICU stay, blood glucose level is maintained either below 1.59 × A1c - 1.59 (mmol/l) (Individualized blood glucose target group), or bellow 10 mmol/l (Conventional blood glucose target group).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
All-cause mortality	28 days after randomization and at ICU discharge
Length of intensive care unit stay	90 days
Need for respiratory support, vasopressor support, dialysis and non-prophylactic antibiotics	during ICU stay (on average 10 days)
incidence and severity of severe hypoglycemia (less than 2.2 mmol/l)	during ICU stay (on average 10 days)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Julien BOHE, MD PhD, Hospices Civils de Lyon - Centre Hospitalier Lyon Sud

Publications and helpful links

General Publications

• Bohe J, Abidi H, Brunot V, Klich A, Klouche K, Sedillot N, Tchenio X, Quenot JP, Roudaut JB, Mottard N, Thiolliere F, Dellamonica J, Wallet F, Souweine B, Lautrette A, Preiser JC, Timsit JF, Vacheron CH, Ait Hssain A, Maucort-Boulch D; CONTROLe INdividualise de la Glycemie (CONTROLING) Study Group. 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 16, 2014
• First Posted (Estimated): September 18, 2014

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: hypoglycemia; ICU; insulin; hyperglycemia; glycated hemoglobin; blood glucose target
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 2013.808; 2013-A00806-39 (Other Identifier: ANSM)