Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients

Critical Illness Clinical Trial

— TGC-fast  

Official title:

Impact of Tight Blood Glucose Control Within Normal Fasting Ranges With Insulin Titration Prescribed by the Leuven Algorithm in Adult Critically Ill Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03665207
• Other study ID #: S61145
• Secondary ID: 2018-000756-17
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 18, 2018
• Est. completion date: November 2026

Study information

• Verified date: June 2023
• Source: KU Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 9230
• Est. completion date: November 2026
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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 included in an IMP-RCT of which the PI indicates that co-inclusion is prohibited
• 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

Related Conditions & MeSH terms

• Critical Illness
• Hyperglycemia

Intervention

Drug:
• Insulin
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.

Locations

Country	Name	City	State
Belgium	Department of Intensive Care Medicine, University Hospital Ghent	Ghent
Belgium	Department of Intensive Care Medicine, Jessa Hospital Hasselt	Hasselt
Belgium	Department of Intensive Care Medicine, University Hospitals Leuven	Leuven
Belgium	Medical Intensive Care Unit, University Hospitals Leuven	Leuven

Sponsors (3)

Lead Sponsor	Collaborator
KU Leuven	Research Foundation Flanders, Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biochemical markers on blood samples	including amino acid levels, blood lipid levels, cytokines, hypothalamic-pituitary hormones, glucagon, C-peptide, (epi)genetic markers	up to 4 years post randomization
Other	Rate of patients with muscle degeneration during ICU stay	assessed by microscopy	up to 30 days post randomization (in selected centers)
Other	Biochemical markers in muscle tissue during ICU stay	including tissular glucose and metabolites, lipid metabolites, myofibrillary proteins, mitochondrial complex activity, autophagy markers, proteasome activity, (epi)genetic markers	up to 30 days post randomization (in selected centers)
Other	Rate of patients with pathological cellular alterations in fat tissue during ICU stay	assessed by microscopy	up to 30 days post randomization (in selected centers)
Other	Biochemical markers in fat tissue during ICU stay	including tissular glucose and metabolites, lipid metabolites, mitochondrial complex activity, autophagy markers, (epi)genetic markers	up to 30 days post randomization (in selected centers)
Other	Rate of patients with muscle degeneration	assessed by microscopy	up to 4 years post randomization (in selected centers)
Other	Biochemical markers in muscle tissue	including tissular glucose and metabolites, lipid metabolites, myofibrillary proteins, mitochondrial complex activity, autophagy markers, proteasome activity, (epi)genetic markers	up to 4 years post randomization (in selected centers)
Other	Rate of patients with pathological cellular alterations in fat tissue	assessed by microscopy	up to 4 years post randomization (in selected centers)
Other	Biochemical markers in fat tissue	including tissular glucose and metabolites, lipid metabolites, mitochondrial complex activity, autophagy markers, (epi)genetic markers	up to 4 years post randomization (in selected centers)
Primary	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	ICU Mortality		up to 1 year after randomization (with and without censoring at 90 days post randomization)
Secondary	Hospital Mortality		up to 1 year after randomization (with and without censoring at 90 days post randomization)
Secondary	90-day mortality		up to 90 days post randomization
Secondary	Blood glucose concentrations in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Duration of ICU dependency	crude number of days with need for vital organ support and time to live discharge from ICU	up to 90 days post randomization
Secondary	Length of stay in hospital		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Time to (live) discharge from hospital		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Incidence of new infections in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Type of new infections in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Duration of antibiotic treatment in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Time course of daily C-reactive protein in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Time to final (live) weaning from mechanical respiratory support in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Number of participants with need for a tracheostomy during ICU stay		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Presence of clinical, electrophysiological and morphological signs of respiratory and peripheral muscle weakness in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization (in selected centers)
Secondary	Incidence of acute kidney injury in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Duration of acute kidney injury		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Rate of recovery from acute kidney injury		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Number of participants with need for new renal replacement therapy in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Rate of recovery from new renal replacement therapy		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Number of participants with need for hemodynamic support in ICU	Hemodynamic support is defined as the need for either pharmacological (inotropes/vasopressors) and/or mechanical hemodynamic support.	up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Duration of hemodynamic support in ICU		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Time to (live) weaning from hemodynamic support		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Time course of markers of liver dysfunction in ICU	including transaminases, gamma-glutamyltransferase, alkaline phosphatase and bilirubin	up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Number of readmissions to the ICU within 48 hours after discharge		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Incidence of delirium in ICU (in selected centers)		up to 1 year post randomization, with and without censoring at 90 days post randomization
Secondary	Rehabilitation/functional outcome	including the score obtained from the 36-item short form health survey (SF-36). The score ranges from 0 to 100, with 100 being the best possible outcome.	up to 2 years post randomization
Secondary	Rehabilitation/functional outcome in patients with brain injury	including the score obtained on the modified Rankin scale. The score ranges from 0 to 6, with 0 being the best possible outcome.	up to 1 year post randomization
Secondary	Rehabilitation/functional outcome in patients with brain injury	including the score obtained on the extended Glasgow outcome scale. The score ranges from 1 to 8, with 8 being the best possible outcome.	up to 1 year post randomization
Secondary	Blood lipid concentrations in ICU		up to 4 years post randomization (in selected centers)
Secondary	Muscle strength	including handgrip strength as % of the predicted value	up to 4 years post randomization (in selected centers)
Secondary	Rehabilitation/Functional outcome	including the 6-minutes walking distance in meter	up to 4 years post randomization (in selected centers)
Secondary	Rehabilitation/Functional outcome	including the score obtained from the SF-36 health survey. The score ranges from 0 to 100, with 100 being the best possible outcome.	up to 4 years post randomization (in selected centers)
Secondary	Rate of recovery of organ function		up to 4 years post randomization (in selected centers)
Secondary	Survival		up to 4 years post randomization (in selected centers)
Secondary	Use of intensive care resources during index hospitalization		up to 1 year post randomization