Clinical trial NCT00410852: Efficacy and Safety of Three Insulin Protocols in Medical Intensive Care Unit Patients
Official title: Randomized Study to Evaluate the Efficacy and Safety of Two Endovenous Insulin Protocols and a Subcutaneous Insulin Protocol in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intensive Care
Keywords: Insulin
Hyperglycemia
Hypoglycemia
Intensive care
Critical care
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2006-12-13
Enrollment: 168
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy: mean of patients' median blood glucose during ICU stay
timeFrame: ICU Stay
measure: Safety: incidence of hypoglycemia (≤40 mg/dL)during ICU stay
timeFrame: ICU stay
Secondary outcomes:
measure: Death from any cause
timeFrame: ICU and in-hospital
measure: ICU and hospital length of stay
timeFrame: ICU and in-hospital
measure: Five-day variation in SOFA score
timeFrame: Five days
measure: 90-day health status
timeFrame: 90 days
measure: Days on mechanical ventilation
measure: Initiation of dialysis
measure: Days on antibiotics
measure: Days on inotropic of vasopressor support
measure: Necessity of red blood cell transfusions
measure: Bilirubin peak
measure: Platelets through
Other outcomes:
Locations:
city: Joinville
country: Brazil
facility: Complexo Hospitalar UNIMED
state: Santa Catarina
city: Joinville
country: Brazil
facility: Hospital Dona Helena
state: Santa Catarina
city: Joinville
country: Brazil
facility: Hospital Regional Sao Jose
state: Santa Catarina
city: Santo Andre
country: Brazil
facility: Hospital Estadual Mario Covas
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Alexandre B Cavalcanti, MD
role: STUDY_CHAIR
affiliation: Hospital Israelita Albert Einstein
name: Eliezer Silva, PhD
role: STUDY_DIRECTOR
affiliation: Departamento de Medicina Preventiva, Faculdade de Medicina da Universidade de Sao Paulo
name: Jose Eluf-Neto, PhD
role: STUDY_DIRECTOR
affiliation: Hospital Regional Sao Jose
name: Milton Caldeira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Hospitalar UNIMED
name: Glauco Westphal, MD
role: PRINCIPAL_INVESTIGATOR
References: