Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients

NCT03665207 | Active Not Recruiting Phase 3

• 2 other identifiers: S611452018-000756-17
• Study Type: interventional
• Target: 9,230
• Locations: 1 country
• Sites: 4

Brief Summary

Critically ill patients usually develop hyperglycemia, which is associated with an increased risk of morbidity and mortality. Controversy exists on whether targeting normal blood glucose concentrations with insulin therapy, referred to as tight blood glucose control (TGC) improves outcome of these patients, as compared to tolerating hyperglycemia. It remains unknown whether TGC, when applied with optimal tools to avoid hypoglycemia, is beneficial in a context of withholding early parenteral nutrition. The TGC-fast study hypothesizes that TGC is beneficial in adult critically ill patients not receiving early parenteral nutrition, as compared to tolerating hyperglycemia.

Conditions

Critical Illness; Hyperglycemia

Outcome Measures

Primary Outcomes (1)

• Duration of ICU dependency

  crude number of days with need for vital organ support and time to live discharge from ICU

  up to 1 year after randomization

Secondary Outcomes (35)

• ICU Mortality

  up to 1 year after randomization (with and without censoring at 90 days post randomization)

• Hospital Mortality

  up to 1 year after randomization (with and without censoring at 90 days post randomization)

• 90-day mortality

  up to 90 days post randomization

• Blood glucose concentrations in ICU

  up to 1 year post randomization, with and without censoring at 90 days post randomization

• Duration of ICU dependency

  up to 90 days post randomization

Other Outcomes (9)

• Biochemical markers on blood samples

  up to 4 years post randomization

• Rate of patients with muscle degeneration during ICU stay

  up to 30 days post randomization (in selected centers)

• Biochemical markers in muscle tissue during ICU stay

  up to 30 days post randomization (in selected centers)

Study Arms (2)

Tight glucose control

EXPERIMENTAL

Target normal fasting blood glucose concentrations (80-110 mg/dl) with insulin therapy, administered through continuous intravenous infusion.

Drug: Insulin

Liberal glucose control

ACTIVE COMPARATOR

Tolerate hyperglycemia up to 215 mg/dl. In patients requiring insulin therapy, insulin will be titrated to target blood glucose concentrations between 180 and 215 mg/dl.

Drug: Insulin

Interventions

Insulin DRUG

When blood glucose exceeds the preset target, insulin will be administered through continuous intravenous infusion. Insulin will be titrated according to frequent measurement of blood glucose and with use of the LOGIC-insulin algorithm in the experimental group. The intervention will be stopped upon ICU discharge, or until the patient is able to resume oral feeding, or until the patient no longer has a central venous catheter, whatever comes first.

Liberal glucose control; Tight glucose control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Adult patient (18 years or older) admitted to a participating intensive care unit (ICU)

You may not qualify if:

• Patients with a do not resuscitate (DNR) order at the time of ICU admission
• Patients expected to die within 12 hours after ICU admission (= moribund patients)
• Patients able to receive oral feeding (not critically ill)
• Patients without arterial and without central venous line and without imminent need to place it as part of ICU management (not critically ill)
• Patients previously included in the trial (when readmission is within 48 hours post ICU discharge, the trial intervention will be resumed)
• Patients transferred from a non-participating ICU with a pre-admission ICU stay \>7 days
• Patients planned to receive parenteral nutrition during the first week in ICU
• Patients suffering from diabetic ketoacidotic or hyperosmolar coma on ICU admission
• Patients with inborn metabolic diseases
• Patients with insulinoma
• Patients known to be pregnant or lactating
• Informed consent refusal

Sponsors & Collaborators

• KU Leuven: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Research Foundation Flanders: collaborator

Study Sites (4)

Department of Intensive Care Medicine, University Hospital Ghent

Ghent, 9000, Belgium

Location

Department of Intensive Care Medicine, Jessa Hospital Hasselt

Hasselt, 3500, Belgium

Location

Department of Intensive Care Medicine, University Hospitals Leuven

Leuven, 3000, Belgium

Location

Medical Intensive Care Unit, University Hospitals Leuven

Leuven, 3000, Belgium

Location

Related Publications (8)

• van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. doi: 10.1056/NEJMoa011300.

  PMID: 11794168 BACKGROUND

• Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006 Feb 2;354(5):449-61. doi: 10.1056/NEJMoa052521.

  PMID: 16452557 BACKGROUND

• Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, Mesotten D, Casaer MP, Meyfroidt G, Ingels C, Muller J, Van Cromphaut S, Schetz M, Van den Berghe G. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet. 2009 Feb 14;373(9663):547-56. doi: 10.1016/S0140-6736(09)60044-1. Epub 2009 Jan 26.

  PMID: 19176240 BACKGROUND

• NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26;360(13):1283-97. doi: 10.1056/NEJMoa0810625. Epub 2009 Mar 24.

  PMID: 19318384 BACKGROUND

• Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011 Aug 11;365(6):506-17. doi: 10.1056/NEJMoa1102662. Epub 2011 Jun 29.

  PMID: 21714640 BACKGROUND

• Fivez T, Kerklaan D, Mesotten D, Verbruggen S, Wouters PJ, Vanhorebeek I, Debaveye Y, Vlasselaers D, Desmet L, Casaer MP, Garcia Guerra G, Hanot J, Joffe A, Tibboel D, Joosten K, Van den Berghe G. Early versus Late Parenteral Nutrition in Critically Ill Children. N Engl J Med. 2016 Mar 24;374(12):1111-22. doi: 10.1056/NEJMoa1514762. Epub 2016 Mar 15.

  PMID: 26975590 BACKGROUND

• Gunst J, Debaveye Y, Guiza F, Dubois J, De Bruyn A, Dauwe D, De Troy E, Casaer MP, De Vlieger G, Haghedooren R, Jacobs B, Meyfroidt G, Ingels C, Muller J, Vlasselaers D, Desmet L, Mebis L, Wouters PJ, Stessel B, Geebelen L, Vandenbrande J, Brands M, Gruyters I, Geerts E, De Pauw I, Vermassen J, Peperstraete H, Hoste E, De Waele JJ, Herck I, Depuydt P, Wilmer A, Hermans G, Benoit DD, Van den Berghe G; TGC-Fast Collaborators. Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU. N Engl J Med. 2023 Sep 28;389(13):1180-1190. doi: 10.1056/NEJMoa2304855.

  PMID: 37754283 DERIVED

• Gunst J, Mebis L, Wouters PJ, Hermans G, Dubois J, Wilmer A, Hoste E, Benoit D, Van den Berghe G. Impact of tight blood glucose control within normal fasting ranges with insulin titration prescribed by the Leuven algorithm in adult critically ill patients: the TGC-fast randomized controlled trial. Trials. 2022 Sep 19;23(1):788. doi: 10.1186/s13063-022-06709-8.

  PMID: 36123593 DERIVED

MeSH Terms

Conditions

Critical Illness; Hyperglycemia

Interventions

Insulin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Greet Van den Berghe, MD, PhD

  KU Leuven

  STUDY DIRECTOR

• Jan Gunst, MD, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor, Head of the clinical department and laboratory of intensive care medicine

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: September 11, 2018
• Study Start: September 18, 2018
• Primary Completion: November 30, 2022
• Study Completion (Estimated): November 1, 2026
• Last Updated: June 5, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)