The effect of strict blood glucose control within normal fasting ranges, with insulin adjusted according to the Leuven algorithm, in adult critically ill patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

1 Sep 2018 → ongoing

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Research Foundation - Flanders (FWO-Vlaanderen)

External identifiers

EU CT number

2023-510358-17-00

EudraCT number

2018-000756-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The purpose of the study is to investigate whether strictly targeting normal fasting ranges for blood glucose with use of a validated algorithm is clinically superior to tolerating hyperglycemia in adult critically ill patients in the context of withholding parenteral nutrition during the first week in the intensive care unit (ICU). The primary objective is to study the short-term clinical impact of the studied intervention (short-term morbidity and mortality).

Secondary objectives 3

1. To study the long-term impact of the intervention (morbidity and mortality)
2. To study the economic impact (healthcare resources)
3. To study the pathophysiological mechanisms involved (depending on additional funding)

Conditions and MedDRA coding

Hyperglycemia in critically ill patients (stress hyperglycemia)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. adult (≥18 years of age)
2. admitted to one of the participating intensive care units

Exclusion criteria 12

1. Patients with a DNR (do not resuscitate) order at the time of ICU admission
2. Patients expected to die within 12 hours after ICU admission (= moribund patients)
3. Patients able to receive oral feeding (not critically ill)
4. Patients without arterial and without central venous line and without imminent need to place it as part of ICU management (not critically ill)
5. Patients previously included in the trial (when readmission is within 48 hours post ICU discharge, the trial intervention will be resumed)
6. Inclusion in an IMP-RCT of which the PI indicates that co-inclusion specifically in TGC-fast is prohibited
7. Patients transferred from a non-participating ICU with a pre-admission ICU stay >7 days
8. Patients planned to receive parenteral nutrition during the first week in ICU
9. Patients suffering from diabetic ketoacidotic or hyperosmolar coma on ICU admission
10. Patients with inborn metabolic diseases
11. Patients with insulinoma
12. Patients known to be pregnant or lactating

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The duration of ICU dependency (defined as the crude number of days with need for vital organ support and as the time to live discharge from ICU to account for death as competing risk)

Secondary endpoints 30

1. Glucose metrics in ICU, with and without censoring at 90 days (mean/median morning blood glucose concentration, mean daily blood glucose concentration, incidence of moderate and severe hypoglycemia during ICU stay, peak blood glucose concentration after hypoglycemic event, duration of hypoglycemia, number of hypoglycemic events per patient, minimum and maximum blood glucose concentration per day, time within blood glucose target range, blood glucose variability, hyperglycemic index)
2. Mortality in ICU and in hospital, with and without censoring at 90 days
3. Mortality 90 days post randomization
4. Hospital length of stay, with and without censoring at 90 days
5. Time to (live) discharge from hospital, with and without censoring at 90 days
6. Time to final (live) weaning from mechanical respiratory support, with and without censoring at 90 days
7. The duration of ICU dependency (defined as the crude number of days with need for vital organ support and as the time to live discharge from ICU to account for death as competing risk), with censoring at 90 days
8. The incidence of new infections during ICU stay, with and without censoring at 90 days
9. The need for tracheostomy during ICU stay, with and without censoring at 90 days
10. Presence of clinical, electrophysiological and morphological signs of respiratory and peripheral muscle weakness during ICU stay in patient subgroups in selected centers, with and without censoring at 90 days
11. The presence or absence of new kidney injury during ICU stay, and duration and recovery herefrom, with and without censoring at 90 days
12. The need for new initiation of renal replacement therapy in ICU (incidence, duration and recovery hereof), with and without censoring at 90 days
13. The need for hemodynamic support during ICU stay, its duration and the time to (live) weaning from hemodynamic support, with and without censoring at 90 days
14. The incidence of new-onset atrial fibrillation and recurrence of pre-existing atrial fibrillation during ICU stay in selected centers, with and without censoring at 90 days
15. The incidence of major adverse cardiovascular events (MACE; non-fatal myocardial infarction, non-fatal stroke, low cardiac output syndrome, and cardiovascular death) during ICU stay in selected centers, with and without censoring at 90 days
16. The presence or absence of signs of liver dysfunction in ICU, with and without censoring at 90 days
17. The duration of antibiotic treatment during ICU stay, with and without censoring at 90 days
18. The incidence of bacteremia, and of airway, urinary tract, wound and other infections acquired during ICU stay, with and without censoring at 90 days
19. Peak and time profile of C-reactive protein concentrations during ICU stay, with and without censoring at 90 days
20. The number of readmissions to the ICU within 48 hours after discharge, with and without censoring at 90 days
21. The presence or absence of delirium during ICU stay (in selected centers), with and without censoring at 90 days
22. Biochemical, metabolic, immunological, inflammatory, cardiac and (epi)genetic markers on blood and tissue samples up to 5 years post randomization (depending on additional funding and in selected centers)
23. Muscle strength, rehabilitation, recovery of organ function and survival up to 5 years post randomization in selected centers and subgroups of patients (depending on additional funding)
24. Long-term functional outcome: For all patients: a validated health questionnaire (Short Form 36, SF-36) 2 years after inclusion
25. Subgroup of brain-injured patients: additional functional outcome after 6 and 12 months (extended Glasgow outcome scale and/or modified Rankin scale)
26. Survival and Barthel index (index obtained by verbal questionnaire) up to 5 years post randomization, in selected centers
27. Use of intensive care resources (costs for hospitalization, for honoraria for medical and allied healthcare services, for pharmacy, for blood products, for clinical chemistry, for radiology, for graft products and for other expenses)
28. The presence or absence of new-onset diabetes mellitus diagnosed after enrolment in the study, up to 5 years post randomization, and, if applicable, the timing of diagnosis and current treatment (e.g. diet only, antidiabetic drugs, insulin or other parenteral treatment), in selected centers
29. The presence or absence of pancreas or pancreatic islet transplantation, up to 5 years post randomization, and, if applicable, the timing of transplantation, in selected centers
30. The presence or absence of end stage renal disease (ESRD) treated with maintenance renal replacement therapy (RRT) or kidney transplantation, at up to 5 years post randomization, and, if applicable, the timing of initiation and the modality of RRT (in-center hemodialysis, home hemodialysis or peritoneal dialysis), in selected centers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Greet Van den Berghe

Public contact point

Organisation

UZ Leuven

Contact name

Greet Van den Berghe

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications