Efficacy and Safety of Three Insulin Protocols in Medical Intensive Care Unit Patients

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of three insulin algorithms in medical ICU patients (MICU).

Detailed Description
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Strict glycemic control has been recommended for critically ill patients. However, its implementation may face difficulties with increased nursing workload, inadequate glucose control and higher risk of hypoglycemia. We designed a computer guided protocol to adjust endovenous insulin infusion aiming glucose levels between 100mg/dl and 130 mg/dl. This trial evaluates the efficacy and safety of this protocol (algorithm A), compared to a standard endovenous insulin infusion protocol (algorithm B) and a conventional subcutaneous insulin protocol (algorithm C). Methods : MICU patients with at least one blood glucose ≥ 150 mg/dL and who are on mechanical ventilation, or had SIRS, or are admitted because of trauma or burn will be randomized to one of the following treatments: algorithm A - continuous insulin infusion with adjustments guided by hand held device or desktop software targeting glucose levels between 100mg/dL-130mg/dL; algorithm B - continuous insulin aiming glucose levels between 80mg/dl-110mg/dl using Van den Berghe's insulin protocol; algorithm C - conventional treatment - intermittent subcutaneous administration of insulin if blood glucose levels exceeds 150mg/dL; insulin will be administered as IV boluses in hypotensive patients. The randomization list was generated in blocks of six by computer software. Patients will be randomly assigned in a 1:1:1 ratio to have their glucose controlled by one of the three insulin algorithms with the use of a central, computerized system accessed by Internet, permitting concealment of allocation list. Randomization will be stratified according to study site. The study is planned to enroll 165 patients in order to have 80% power to detect a 20mg/dl difference in blood glucose means between groups, assuming standard deviation equal to 33 mg/dl and two-tailed alpha equal to 0.05. Efficacy will be measured by the mean of patients' median blood glucose and safety measured by the incidence of hypoglycemia (≤40 mg/dL). Analysis will follow the intention-to-treat principle.

Official Title
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Randomized Study to Evaluate the Efficacy and Safety of Two Endovenous Insulin Protocols and a Subcutaneous Insulin Protocol in Critically Ill Patients

Conditions
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Intensive Care

Intervention / Treatment
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* Procedure: Computer-assisted IV insulin infusion protocol (algorithm A)
* Procedure: Leuven Strict glycemic control protocol (Algorithm B)
* Procedure: Conventional Intermittent Insulin Protocol (Algorithm C)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Criteria 1, 2 and 3 must be present: Clinical patients admitted to an Intensive Care Unit At least one blood glucose measurement >= 150 mg/dL (capilar, venous or arterial blood) At least one of the following: Patient on mechanical ventilation for an acute process, with expected duration of mechanical ventilation of at least 24 hours Polytrauma patients Severe burn patients Systemic Inflammatory Response Syndrome (modified criteria), with at least three of the following: core temperature >=38°C or <=36°C; heart rate >=90 beats/min, except in patients with a medical condition or receiving a medication known to prevent tachycardia; respiratory heart rate >= 20 breaths/min or a PaCO2 <=32mmHg, or the use of mechanical ventilation for an acute process; white-cell count of >=12.000/mm3 or <=4.000/mm3 or a differential count showing >10% percent immature neutrophils Exclusion Criteria: Age < 21 years Surgical patients (surgery less than 24hs before admission to ICU) Diabetic ketoacidosis Non-ketotic hyperosmolar state Patients with defined diagnosis of brain death Moribund state in which death is perceived to be imminent

Ages Eligible for Study
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Minimum Age: 21 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Procedure: Computer-assisted IV insulin infusion protocol (algorithm A)<br>* Computer assisted insulin protocol (CAIP), with continuous intravenous insulin adjustments aiming blood glucose levels between 100 mg/dl and 130 mg/dl.<br>|
| Experimental: B<br> | Procedure: Leuven Strict glycemic control protocol (Algorithm B)<br>* Leuven protocol: continuous intravenous insulin infusion aimiming blood glucose levels between 80mg/dl and 110mg/dl.<br>|
| Active Comparator: C<br> | Procedure: Conventional Intermittent Insulin Protocol (Algorithm C)<br>* Conventional treatment: intermitent subcutaneous insulin according to a sliding scale, starting with blood glucose levels higher than 150mg/dl.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: mean of patients' median blood glucose during ICU stay |  | ICU Stay | 
| Safety: incidence of hypoglycemia (≤40 mg/dL)during ICU stay |  | ICU stay | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from any cause |  | ICU and in-hospital | 
| ICU and hospital length of stay |  | ICU and in-hospital | 
| Five-day variation in SOFA score |  | Five days | 
| 90-day health status |  | 90 days | 
| Days on mechanical ventilation |  |  | 
| Initiation of dialysis |  |  | 
| Days on antibiotics |  |  | 
| Days on inotropic of vasopressor support |  |  | 
| Necessity of red blood cell transfusions |  |  | 
| Bilirubin peak |  |  | 
| Platelets through |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, Hyperglycemia, Hypoglycemia, Intensive care, Critical care