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

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ClinicalTrials.gov Identifier: NCT03665207
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : October 1, 2018
Sponsor:
Collaborators:
Universitaire Ziekenhuizen Leuven
Research Foundation Flanders
Information provided by (Responsible Party):
Greet Van den Berghe, KU Leuven

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.

Condition or disease Intervention/treatment Phase
Critical Illness Hyperglycemia Drug: Insulin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 18, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tight glucose control
Target normal fasting blood glucose concentrations (80-110 mg/dl) with insulin therapy, administered through continuous intravenous infusion.
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.

Active Comparator: Liberal glucose control
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
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 Measures :
  1. Duration of ICU dependency [ Time Frame: up to 1 year after randomization ]
    crude number of days with need for vital organ support and time to live discharge from ICU


Secondary Outcome Measures :
  1. ICU Mortality [ Time Frame: up to 1 year after randomization (with and without censoring at 90 days post randomization) ]
  2. Hospital Mortality [ Time Frame: up to 1 year after randomization (with and without censoring at 90 days post randomization) ]
  3. 90-day mortality [ Time Frame: up to 90 days post randomization ]
  4. Blood glucose concentrations in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  5. Duration of ICU dependency [ Time Frame: up to 90 days post randomization ]
    crude number of days with need for vital organ support and time to live discharge from ICU

  6. Length of stay in hospital [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  7. Time to (live) discharge from hospital [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  8. Incidence of new infections in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  9. Type of new infections in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  10. Duration of antibiotic treatment in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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) ]
  15. Incidence of acute kidney injury in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  16. Duration of acute kidney injury [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  17. Rate of recovery from acute kidney injury [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  18. 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 ]
  19. 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 ]
  20. Number of participants with need for hemodynamic support in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
    Hemodynamic support is defined as the need for either pharmacological (inotropes/vasopressors) and/or mechanical hemodynamic support.

  21. Duration of hemodynamic support in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  22. Time to (live) weaning from hemodynamic support [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
  23. Time course of markers of liver dysfunction in ICU [ Time Frame: up to 1 year post randomization, with and without censoring at 90 days post randomization ]
    including transaminases, gamma-glutamyltransferase, alkaline phosphatase and bilirubin

  24. 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 ]
  25. 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 ]
  26. Rehabilitation/functional outcome [ Time Frame: up to 2 years post randomization ]
    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.

  27. Rehabilitation/functional outcome in patients with brain injury [ Time Frame: up to 1 year post randomization ]
    including the score obtained on the modified Rankin scale. The score ranges from 0 to 6, with 0 being the best possible outcome.

  28. Rehabilitation/functional outcome in patients with brain injury [ Time Frame: up to 1 year post randomization ]
    including the score obtained on the extended Glasgow outcome scale. The score ranges from 1 to 8, with 8 being the best possible outcome.

  29. Blood lipid concentrations in ICU [ Time Frame: up to 4 years post randomization (in selected centers) ]
  30. Muscle strength [ Time Frame: up to 4 years post randomization (in selected centers) ]
    including handgrip strength as % of the predicted value

  31. Rehabilitation/Functional outcome [ Time Frame: up to 4 years post randomization (in selected centers) ]
    including the 6-minutes walking distance in meter

  32. Rehabilitation/Functional outcome [ Time Frame: up to 4 years post randomization (in selected centers) ]
    including the score obtained from the SF-36 health survey. The score ranges from 0 to 100, with 100 being the best possible outcome.

  33. Rate of recovery of organ function [ Time Frame: up to 4 years post randomization (in selected centers) ]
  34. Survival [ Time Frame: up to 4 years post randomization (in selected centers) ]
  35. Use of intensive care resources during index hospitalization [ Time Frame: up to 1 year post randomization ]

Other Outcome Measures:
  1. Biochemical markers on blood samples [ Time Frame: up to 4 years post randomization ]
    including amino acid levels, blood lipid levels, cytokines, hypothalamic-pituitary hormones, glucagon, C-peptide, (epi)genetic markers

  2. Rate of patients with muscle degeneration during ICU stay [ Time Frame: up to 30 days post randomization (in selected centers) ]
    assessed by microscopy

  3. Biochemical markers in muscle tissue during ICU stay [ Time Frame: up to 30 days post randomization (in selected centers) ]
    including tissular glucose and metabolites, lipid metabolites, myofibrillary proteins, mitochondrial complex activity, autophagy markers, proteasome activity, (epi)genetic markers

  4. Rate of patients with pathological cellular alterations in fat tissue during ICU stay [ Time Frame: up to 30 days post randomization (in selected centers) ]
    assessed by microscopy

  5. Biochemical markers in fat tissue during ICU stay [ Time Frame: up to 30 days post randomization (in selected centers) ]
    including tissular glucose and metabolites, lipid metabolites, mitochondrial complex activity, autophagy markers, (epi)genetic markers

  6. Rate of patients with muscle degeneration [ Time Frame: up to 4 years post randomization (in selected centers) ]
    assessed by microscopy

  7. Biochemical markers in muscle tissue [ Time Frame: up to 4 years post randomization (in selected centers) ]
    including tissular glucose and metabolites, lipid metabolites, myofibrillary proteins, mitochondrial complex activity, autophagy markers, proteasome activity, (epi)genetic markers

  8. Rate of patients with pathological cellular alterations in fat tissue [ Time Frame: up to 4 years post randomization (in selected centers) ]
    assessed by microscopy

  9. Biochemical markers in fat tissue [ Time Frame: up to 4 years post randomization (in selected centers) ]
    including tissular glucose and metabolites, lipid metabolites, mitochondrial complex activity, autophagy markers, (epi)genetic markers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 already enrolled in another randomized controlled trial (RCT) powered for clinical endpoints
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03665207


Contacts
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Contact: Greet Van den Berghe, MD, PhD +32 16 344021 greet.vandenberghe@kuleuven.be
Contact: Jan Gunst, MD, PhD +32 16 344021 jan.gunst@kuleuven.be

Locations
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Belgium
Department of Intensive Care Medicine, University Hospital Antwerp Not yet recruiting
Antwerp, Belgium, 2650
Contact: Philippe Jorens, MD, PhD    +32 3 8213635    Philippe.Jorens@uza.be   
Principal Investigator: Philippe Jorens, MD, PhD         
Department of Intensive Care Medicine, University Hospital Ghent Not yet recruiting
Ghent, Belgium, 9000
Contact: Dominique Benoit, MD, PhD    +32 9 3322775    Dominique.Benoit@UGent.be   
Principal Investigator: Dominique Benoit, MD, PhD         
Sub-Investigator: Eric Hoste, MD, PhD         
Sub-Investigator: Harlinde Peperstraete, MD         
Sub-Investigator: Joris Vermassen, MD         
Department of Intensive Care Medicine, Jessa Hospital Hasselt Not yet recruiting
Hasselt, Belgium, 3500
Contact: Jasperina Dubois, MD    + 32 11 308971    jasperina.dubois@jessazh.be   
Principal Investigator: Jasperina Dubois, MD         
Department of Intensive Care Medicine, University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
Contact: Greet Van den Berghe, MD, PhD    +32 16 344021    greet.vandenberghe@kuleuven.be   
Contact: Jan Gunst, MD, PhD    +32 16 344021    jan.gunst@kuleuven.be   
Principal Investigator: Greet Van den Berghe, MD, PhD         
Principal Investigator: Jan Gunst, MD, PhD         
Medical Intensive Care Unit, University Hospitals Leuven Not yet recruiting
Leuven, Belgium, 3000
Contact: Greet Hermans, MD, PhD    +32 16 344275    greet.hermans@uzleuven.be   
Principal Investigator: Greet Hermans, MD, PhD         
Sub-Investigator: Alexander Wilmer, MD, PhD         
Sponsors and Collaborators
KU Leuven
Universitaire Ziekenhuizen Leuven
Research Foundation Flanders
Investigators
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Study Director: Greet Van den Berghe, MD, PhD KU Leuven
Principal Investigator: Jan Gunst, MD, PhD KU Leuven

Publications:

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Responsible Party: Greet Van den Berghe, Full professor, Head of the clinical department and laboratory of intensive care medicine, KU Leuven
ClinicalTrials.gov Identifier: NCT03665207     History of Changes
Other Study ID Numbers: S61145
2018-000756-17 ( EudraCT Number )
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: October 1, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Hyperglycemia
Critical Illness
Disease Attributes
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs