Clinical trial NCT03665207: Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Critical Illness
Hyperglycemia
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: Universitaire Ziekenhuizen KU Leuven
name: Research Foundation Flanders
First posted: 2018-09-11
Enrollment: 9230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Duration of ICU dependency
timeFrame: up to 1 year after randomization
Secondary outcomes:
measure: ICU Mortality
timeFrame: up to 1 year after randomization (with and without censoring at 90 days post randomization)
measure: Hospital Mortality
timeFrame: up to 1 year after randomization (with and without censoring at 90 days post randomization)
measure: 90-day mortality
timeFrame: up to 90 days post randomization
measure: Blood glucose concentrations in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Duration of ICU dependency
timeFrame: up to 90 days post randomization
measure: Length of stay in hospital
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Time to (live) discharge from hospital
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Incidence of new infections in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Type of new infections in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Duration of antibiotic treatment in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Time course of daily C-reactive protein in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Time to final (live) weaning from mechanical respiratory support in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Number of participants with need for a tracheostomy during ICU stay
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Presence of clinical, electrophysiological and morphological signs of respiratory and peripheral muscle weakness in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization (in selected centers)
measure: Incidence of acute kidney injury in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Duration of acute kidney injury
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Rate of recovery from acute kidney injury
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Number of participants with need for new renal replacement therapy in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Rate of recovery from new renal replacement therapy
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Number of participants with need for hemodynamic support in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Duration of hemodynamic support in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Time to (live) weaning from hemodynamic support
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Time course of markers of liver dysfunction in ICU
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Number of readmissions to the ICU within 48 hours after discharge
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Incidence of delirium in ICU (in selected centers)
timeFrame: up to 1 year post randomization, with and without censoring at 90 days post randomization
measure: Rehabilitation/functional outcome
timeFrame: up to 2 years post randomization
measure: Rehabilitation/functional outcome in patients with brain injury
timeFrame: up to 1 year post randomization
measure: Rehabilitation/functional outcome in patients with brain injury
timeFrame: up to 1 year post randomization
measure: Blood lipid concentrations in ICU
timeFrame: up to 4 years post randomization (in selected centers)
measure: Muscle strength
timeFrame: up to 4 years post randomization (in selected centers)
measure: Rehabilitation/Functional outcome
timeFrame: up to 4 years post randomization (in selected centers)
measure: Rehabilitation/Functional outcome
timeFrame: up to 4 years post randomization (in selected centers)
measure: Rate of recovery of organ function
timeFrame: up to 4 years post randomization (in selected centers)
measure: Survival
timeFrame: up to 4 years post randomization (in selected centers)
measure: Use of intensive care resources during index hospitalization
timeFrame: up to 1 year post randomization
Other outcomes:
measure: Biochemical markers on blood samples
timeFrame: up to 4 years post randomization
measure: Rate of patients with muscle degeneration during ICU stay
timeFrame: up to 30 days post randomization (in selected centers)
measure: Biochemical markers in muscle tissue during ICU stay
timeFrame: up to 30 days post randomization (in selected centers)
measure: Rate of patients with pathological cellular alterations in fat tissue during ICU stay
timeFrame: up to 30 days post randomization (in selected centers)
measure: Biochemical markers in fat tissue during ICU stay
timeFrame: up to 30 days post randomization (in selected centers)
measure: Rate of patients with muscle degeneration
timeFrame: up to 4 years post randomization (in selected centers)
measure: Biochemical markers in muscle tissue
timeFrame: up to 4 years post randomization (in selected centers)
measure: Rate of patients with pathological cellular alterations in fat tissue
timeFrame: up to 4 years post randomization (in selected centers)
measure: Biochemical markers in fat tissue
timeFrame: up to 4 years post randomization (in selected centers)
Locations:
city: Ghent
country: Belgium
facility: Department of Intensive Care Medicine, University Hospital Ghent
city: Hasselt
country: Belgium
facility: Department of Intensive Care Medicine, Jessa Hospital Hasselt
city: Leuven
country: Belgium
facility: Department of Intensive Care Medicine, University Hospitals Leuven
city: Leuven
country: Belgium
facility: Medical Intensive Care Unit, University Hospitals Leuven
Study officials:
affiliation: KU Leuven
name: Greet Van den Berghe, MD, PhD
role: STUDY_DIRECTOR
affiliation: KU Leuven
name: Jan Gunst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.