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

Intensive Care Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00410852
• Other study ID #: FAPESP 2005/50557-5
• Status: Completed
• Phase: N/A
• First received: December 12, 2006
• Last updated: October 31, 2007
• Start date: May 2005
• Est. completion date: March 2007

Study information

• Verified date: October 2007
• Source: Hospital Israelita Albert Einstein
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Criteria 1, 2 and 3 must be present:

1. Clinical patients admitted to an Intensive Care Unit

2. At least one blood glucose measurement >= 150 mg/dL (capilar, venous or arterial blood)

3. At least one of the following:

1. Patient on mechanical ventilation for an acute process, with expected duration of mechanical ventilation of at least 24 hours

2. Polytrauma patients

3. Severe burn patients

4. 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Intensive Care

Intervention

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

Locations

Country	Name	City	State
Brazil	Complexo Hospitalar UNIMED	Joinville	Santa Catarina
Brazil	Hospital Dona Helena	Joinville	Santa Catarina
Brazil	Hospital Regional Sao Jose	Joinville	Santa Catarina
Brazil	Hospital Estadual Mario Covas	Santo Andre	Sao Paulo
Brazil	Hospital Israelita Albert Einstein	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: mean of patients' median blood glucose during ICU stay		ICU Stay
Primary	Safety: incidence of hypoglycemia (=40 mg/dL)during ICU stay		ICU stay
Secondary	Death from any cause		ICU and in-hospital
Secondary	ICU and hospital length of stay		ICU and in-hospital
Secondary	Five-day variation in SOFA score		Five days
Secondary	90-day health status		90 days
Secondary	Days on mechanical ventilation
Secondary	Initiation of dialysis
Secondary	Days on antibiotics
Secondary	Days on inotropic of vasopressor support
Secondary	Necessity of red blood cell transfusions
Secondary	Bilirubin peak
Secondary	Platelets through