Back to results

Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients (TGC-fast)

Primary Purpose

Critical Illness, Hyperglycemia

Status

Active

Phase

Phase 3

Locations

Belgium

Study Type

Interventional

Intervention

Insulin

About this trial

This is an interventional treatment trial for Critical Illness

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Department of Intensive Care Medicine, University Hospital Ghent
Department of Intensive Care Medicine, Jessa Hospital Hasselt
Department of Intensive Care Medicine, University Hospitals Leuven
Medical Intensive Care Unit, University Hospitals Leuven

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tight glucose control

Liberal glucose control

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Duration of ICU dependency

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

Secondary Outcome Measures

ICU Mortality

Hospital Mortality

90-day mortality

Blood glucose concentrations in ICU

Duration of ICU dependency

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

Length of stay in hospital

Time to (live) discharge from hospital

Incidence of new infections in ICU

Type of new infections in ICU

Duration of antibiotic treatment in ICU

Time course of daily C-reactive protein in ICU

Time to final (live) weaning from mechanical respiratory support in ICU

Number of participants with need for a tracheostomy during ICU stay

Presence of clinical, electrophysiological and morphological signs of respiratory and peripheral muscle weakness in ICU

Incidence of acute kidney injury in ICU

Duration of acute kidney injury

Rate of recovery from acute kidney injury

Number of participants with need for new renal replacement therapy in ICU

Rate of recovery from new renal replacement therapy

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.

Duration of hemodynamic support in ICU

Time to (live) weaning from hemodynamic support

Time course of markers of liver dysfunction in ICU

including transaminases, gamma-glutamyltransferase, alkaline phosphatase and bilirubin

Number of readmissions to the ICU within 48 hours after discharge

Incidence of delirium in ICU (in selected centers)

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.

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.

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.

Blood lipid concentrations in ICU

Muscle strength

including handgrip strength as % of the predicted value

Rehabilitation/Functional outcome

including the 6-minutes walking distance in meter

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.

Rate of recovery of organ function

Survival

Use of intensive care resources during index hospitalization

Full Information

NCT ID

NCT03665207

First Posted

August 29, 2018

Last Updated

June 2, 2023

Sponsor

KU Leuven

Collaborators

Universitaire Ziekenhuizen KU Leuven, Research Foundation Flanders

1. Study Identification

Unique Protocol Identification Number

NCT03665207

Brief Title

Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 18, 2018 (Actual)

Primary Completion Date

November 30, 2022 (Actual)

Study Completion Date

November 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

KU Leuven

Collaborators

Universitaire Ziekenhuizen KU Leuven, Research Foundation Flanders

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Illness, Hyperglycemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

9230 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tight glucose control

Arm Type

Experimental

Arm Description

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

Arm Title

Liberal glucose control

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Duration of ICU dependency

Description

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

Time Frame

up to 1 year after randomization

Secondary Outcome Measure Information:

Title

ICU Mortality

Time Frame

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

Title

Hospital Mortality

Time Frame

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

Title

90-day mortality

Time Frame

up to 90 days post randomization

Title

Blood glucose concentrations in ICU

Time Frame

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

Title

Duration of ICU dependency

Description

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

Time Frame

up to 90 days post randomization

Title

Length of stay in hospital

Time Frame

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

Title

Time to (live) discharge from hospital

Time Frame

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

Title

Incidence of new infections in ICU

Time Frame

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

Title

Type of new infections in ICU

Time Frame

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

Title

Duration of antibiotic treatment in ICU

Time Frame

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

Title

Time course of daily C-reactive protein in ICU

Time Frame

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

Title

Time to final (live) weaning from mechanical respiratory support in ICU

Time Frame

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

Title

Number of participants with need for a tracheostomy during ICU stay

Time Frame

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

Title

Presence of clinical, electrophysiological and morphological signs of respiratory and peripheral muscle weakness in ICU

Time Frame

up to 1 year post randomization, with and without censoring at 90 days post randomization (in selected centers)

Title

Incidence of acute kidney injury in ICU

Time Frame

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

Title

Duration of acute kidney injury

Time Frame

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

Title

Rate of recovery from acute kidney injury

Time Frame

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

Title

Number of participants with need for new renal replacement therapy in ICU

Time Frame

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

Title

Rate of recovery from new renal replacement therapy

Time Frame

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

Title

Number of participants with need for hemodynamic support in ICU

Description

Hemodynamic support is defined as the need for either pharmacological (inotropes/vasopressors) and/or mechanical hemodynamic support.

Time Frame

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

Title

Duration of hemodynamic support in ICU

Time Frame

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

Title

Time to (live) weaning from hemodynamic support

Time Frame

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

Title

Time course of markers of liver dysfunction in ICU

Description

including transaminases, gamma-glutamyltransferase, alkaline phosphatase and bilirubin

Time Frame

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

Title

Number of readmissions to the ICU within 48 hours after discharge

Time Frame

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

Title

Incidence of delirium in ICU (in selected centers)

Time Frame

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

Title

Rehabilitation/functional outcome

Description

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.

Time Frame

up to 2 years post randomization

Title

Rehabilitation/functional outcome in patients with brain injury

Description

including the score obtained on the modified Rankin scale. The score ranges from 0 to 6, with 0 being the best possible outcome.

Time Frame

up to 1 year post randomization

Title

Rehabilitation/functional outcome in patients with brain injury

Description

including the score obtained on the extended Glasgow outcome scale. The score ranges from 1 to 8, with 8 being the best possible outcome.

Time Frame

up to 1 year post randomization

Title

Blood lipid concentrations in ICU

Time Frame

up to 4 years post randomization (in selected centers)

Title

Muscle strength

Description

including handgrip strength as % of the predicted value

Time Frame

up to 4 years post randomization (in selected centers)

Title

Rehabilitation/Functional outcome

Description

including the 6-minutes walking distance in meter

Time Frame

up to 4 years post randomization (in selected centers)

Title

Rehabilitation/Functional outcome

Description

including the score obtained from the SF-36 health survey. The score ranges from 0 to 100, with 100 being the best possible outcome.

Time Frame

up to 4 years post randomization (in selected centers)

Title

Rate of recovery of organ function

Time Frame

up to 4 years post randomization (in selected centers)

Title

Survival

Time Frame

up to 4 years post randomization (in selected centers)

Title

Use of intensive care resources during index hospitalization

Time Frame

up to 1 year post randomization

Other Pre-specified Outcome Measures:

Title

Biochemical markers on blood samples

Description

including amino acid levels, blood lipid levels, cytokines, hypothalamic-pituitary hormones, glucagon, C-peptide, (epi)genetic markers

Time Frame

up to 4 years post randomization

Title

Rate of patients with muscle degeneration during ICU stay

Description

assessed by microscopy

Time Frame

up to 30 days post randomization (in selected centers)

Title

Biochemical markers in muscle tissue during ICU stay

Description

including tissular glucose and metabolites, lipid metabolites, myofibrillary proteins, mitochondrial complex activity, autophagy markers, proteasome activity, (epi)genetic markers

Time Frame

up to 30 days post randomization (in selected centers)

Title

Rate of patients with pathological cellular alterations in fat tissue during ICU stay

Description

assessed by microscopy

Time Frame

up to 30 days post randomization (in selected centers)

Title

Biochemical markers in fat tissue during ICU stay

Description

including tissular glucose and metabolites, lipid metabolites, mitochondrial complex activity, autophagy markers, (epi)genetic markers

Time Frame

up to 30 days post randomization (in selected centers)

Title

Rate of patients with muscle degeneration

Description

assessed by microscopy

Time Frame

up to 4 years post randomization (in selected centers)

Title

Biochemical markers in muscle tissue

Description

including tissular glucose and metabolites, lipid metabolites, myofibrillary proteins, mitochondrial complex activity, autophagy markers, proteasome activity, (epi)genetic markers

Time Frame

up to 4 years post randomization (in selected centers)

Title

Rate of patients with pathological cellular alterations in fat tissue

Description

assessed by microscopy

Time Frame

up to 4 years post randomization (in selected centers)

Title

Biochemical markers in fat tissue

Description

including tissular glucose and metabolites, lipid metabolites, mitochondrial complex activity, autophagy markers, (epi)genetic markers

Time Frame

up to 4 years post randomization (in selected centers)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Greet Van den Berghe, MD, PhD

Organizational Affiliation

KU Leuven

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Jan Gunst, MD, PhD

Organizational Affiliation

KU Leuven

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Intensive Care Medicine, University Hospital Ghent

City

Ghent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Department of Intensive Care Medicine, Jessa Hospital Hasselt

City

Hasselt

ZIP/Postal Code

3500

Country

Belgium

Facility Name

Department of Intensive Care Medicine, University Hospitals Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Medical Intensive Care Unit, University Hospitals Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Data sharing will be considered only on a collaborative basis with PIs, after evaluation of the proposed study protocol and statistical analysis plan.

Citations:

PubMed Identifier

11794168

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.

Results Reference

background

PubMed Identifier

16452557

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.

Results Reference

background

PubMed Identifier

19176240

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.

Results Reference

background

PubMed Identifier

19318384

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.

Results Reference

background

PubMed Identifier

21714640

Citation

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.

Results Reference

background

PubMed Identifier

26975590

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.

Results Reference

background

PubMed Identifier

36123593

Citation

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.

Results Reference

derived

Learn more about this trial

Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients

We'll reach out to this number within 24 hrs