Tight Versus Liberal Blood Glucose Control in Adult Critically Ill Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Critical Illness, Hyperglycemia

Intervention / Treatment
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* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tight glucose control<br>Target normal fasting blood glucose concentrations (80-110 mg/dl) with insulin therapy, administered through continuous intravenous infusion. | Drug: Insulin<br>* 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.<br>|
| Active Comparator: Liberal glucose control<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | crude number of days with need for vital organ support and time to live discharge from ICU | up to 90 days post randomization | 
| Length of stay in hospital |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Time to (live) discharge from hospital |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Incidence of new infections in ICU |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Type of new infections in ICU |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Duration of antibiotic treatment in ICU |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Time course of daily C-reactive protein in ICU |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| 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 | 
| 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 | 
| 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) | 
| Incidence of acute kidney injury in ICU |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Duration of acute kidney injury |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Rate of recovery from acute kidney injury |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| 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 | 
| Rate of recovery from new renal replacement therapy |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| 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 | 
| Duration of hemodynamic support in ICU |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| Time to (live) weaning from hemodynamic support |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| 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 | 
| 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 | 
| Incidence of delirium in ICU (in selected centers) |  | up to 1 year post randomization, with and without censoring at 90 days post randomization | 
| 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 | 
| 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 | 
| 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 | 
| Blood lipid concentrations in ICU |  | up to 4 years post randomization (in selected centers) | 
| Muscle strength | including handgrip strength as % of the predicted value | up to 4 years post randomization (in selected centers) | 
| Rehabilitation/Functional outcome | including the 6-minutes walking distance in meter | up to 4 years post randomization (in selected centers) | 
| 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) | 
| Rate of recovery of organ function |  | up to 4 years post randomization (in selected centers) | 
| Survival |  | up to 4 years post randomization (in selected centers) | 
| Use of intensive care resources during index hospitalization |  | up to 1 year post randomization |