Diabetes or With New Hyperglycemia
Conditions
Keywords
ICU, hyperglycemia, glucommander
Brief summary
The study is a multicenter, prospective, open-label randomized study to compare the safety and efficacy of continuous insulin infusion (CII) via a computer-guided(Glucommander) and a standard paper form protocol among the patients hospitalized in a medical intensive care unit (ICU). .
Detailed description
Increasing evidence from observational studies in hospitalized patients with and without diabetes indicates that hyperglycemia is a predictor of poor outcome. Blood glucose control with intensive insulin therapy in patients with acute critical illness reduces the risk of multiorgan failure and systemic infection, and decreases short- and long-term mortality. The use of intravenous insulin infusion is the preferred route of insulin administration for the management of diabetic subjects with diabetic ketoacidosis and nonketotic hyperosmolar state, intraoperative and postoperative care, the postoperative period following heart surgery and organ transplantation, acute myocardial infarction, stroke, and critical care illness. Some of these settings may be characterized by, or associated with, severe or rapidly changing insulin requirements, generalized patient edema, impaired perfusion of subcutaneous sites, requirement for pressor support, and/or use of total parenteral nutrition. In these settings, the intravenous route for insulin administration has been considered superior than the subcutaneous injection of split-mixed regimen of intermediate and regular insulin with respect to rapidity of effect in controlling hyperglycemia, overall ability to achieve glycemic control, and most importantly, preventing hypoglycemic episodes. Recently, several insulin infusion protocols have been reported in the literature; these algorithms and formulas, however, may be confusing and difficult to follow and may increase the risk of dosing errors. To facilitate patients care, insulin algorithms could be placed on a computer and used at the patient bedside to direct the nursing staff administering the intravenous insulin. The Glucommander is one of such computer-derived insulin infusion protocol which has been used successfully in over 5,802 patients with diabetes between 1984 and 1998. The study hypothesizes that management of inpatient hyperglycemia with a computer-guided intravenous infusion protocol will facilitate smoother glycemic control with a lower rate of hypoglycemic events than treatment following a standard insulin infusion algorithm in critically ill patients in medical the ICU. The study also aims to determine differences in glycemic control between treatment with a computer-guided intravenous infusion protocol (Glucommander) and a standard insulin infusion algorithm in critically ill patients in the ICU.
Interventions
DEVICEGlucommander
Glucommander is a Computer-guided Intravenous (IV) insulin infusion protocol used for glycemic control in inpatients. This algorithm directs the administration of IV insulin in response to Blood Glucose (BG) measurement at the patient's bedside. In this study, the Glucommander program was loaded into a PalmOne (Zire 31, Tungsten E2 by Palm Inc.) handheld personal digital assistant (PDA) device. During the infusion, the nurse entered BG levels into the system and the computer recommended the insulin infusion rate and a variable time to check the next glucose testing. An alarm prompted the scheduled glucose check. The insulin infusion followed the formula: Insulin/Hour = Multiplier × (BG- 60).
OTHERStandard insulin infusion algorithm
Standard insulin infusion Algorithm is a standard paper form insulin infusion algorithm. The algorithm is divided into four columns based on empirically determined insulin sensitivity. The first column was for the most insulin-sensitive patients, and the fourth column was for the most insulin resistant patients. The majority of patients are started in the algorithm 1 column. Insulin resistant patients, such as those receiving glucocorticoids or receiving \>80 units of insulin per day as outpatients, started in the algorithm 2 column. The insulin infusion rate was determined by the patient's BG level and was measured hourly until the patient was stable and within the target range. If BG targets were not achieved and the BG had not decreased by at least 60 mg/dL in the preceding hour, the patient was moved to the next column.
Sponsors
Sanofi
Grady Health System
Piedmont Healthcare
University of Tennessee
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females between the ages of 18 and 70 years admitted to a medical ICU 2. A known history of diabetes mellitus or with new hyperglycemia untreated or treated by diet, insulin therapy or with any combination of antidiabetic agents (sulfonylureas, metformin, thiazolidinediones). * Blood glucose greater than 120 mg/dl on ≥ 2 occasions for known, treated diabetics or greater than 140 mg/dl on ≥ 2 occasions for those with new hyperglycemia. 3. Subjects must have an admission blood glucose \< 400 mg/dL, without laboratory evidence of diabetic ketoacidosis (serum bicarbonate \< 18 milliequivalents/L or positive serum or urinary ketones).
Exclusion criteria
1. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state \[38\]. 2. Patients with known HIV, severely impaired renal function (serum creatinine ≥3.0 mg/dl). 3. Patients with mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. 4. Female subjects who are pregnant or breast feeding at time of enrollment into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Blood Glucose (BG) in mg/dl Among Glucommander Group Compared to Standard Insulin Infusion | First 10 days of ICU stay | Daily mean blood glucose concentrations during insulin infusion with the Glucommander and a standard paper form insulin infusion algorithm are measured every day up until 10 days and a mean values of these levels are calculated. The Mean blood glucose concentrations are measured once the target blood glucose levels are achieved after admission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Severe Hypoglycemia Episodes Among the Glucommander Group Compared to Standard Algorithm | First 10 days of ICU stay | Severe hypoglycemia is defined as the blood glucose (BG) levels lower than 40 mg/dL. The number of patients enrolled among both groups with the reports of having the BG levels lower than 40 mg/dL are recorded for duration of 10 days |
| Mean Length of Intensive Care Unit (ICU) in Days Stay Among Glucommander Group Compared to Standard Insulin Infusion Group | During ICU hospitalization, up to 30 days | Mean number of days, the patients stayed in the intensive care unit are measured among glucommander group and standard insulin infusion group. |
| Mean Hospital Length of Stay in Days Among the Glucommander Group Compared to Standard Insulin Infusion | During the complete length of hospitalization, up to 60 days | mean number of days the patients stayed in the hospital are measured among the Glucommander group and standard insulin infusion and compared |
Countries
United States
Participant flow
Recruitment details
4 hospital centers between April 2006 and August 2008.
Pre-assignment details
Of 160 enrolled, 80 were randomized to each group. Among the 80 subjects in glucommander group, 1 died prior to starting infusion and 2 were excluded because of meeting exclusion criteria for the protocol. Among 80 subject in standard group 1 withdrew consent prior to starting infusion and 3 met exclusion criteria. 153 were analyzed
Participants by arm
| Arm | Count |
|---|---|
| Glucommander insulin infusion per Glucommander | 77 |
| Standard Insulin Infusion standard insulin infusion with columnar algorithm | 76 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Standard Insulin Infusion | Glucommander | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 15 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 62 Participants | 114 Participants |
| Age, Continuous | 58.5 years STANDARD_DEVIATION 13.4 | 57.8 years STANDARD_DEVIATION 11 | 58.15 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment United States | 76 participants | 77 participants | 153 participants |
| Sex: Female, Male Female | 37 Participants | 33 Participants | 70 Participants |
| Sex: Female, Male Male | 39 Participants | 44 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 77 | 20 / 76 |
| other Total, other adverse events | 42 / 77 | 41 / 76 |
| serious Total, serious adverse events | 3 / 77 | 4 / 76 |
Outcome results
Primary
Mean Blood Glucose (BG) in mg/dl Among Glucommander Group Compared to Standard Insulin Infusion
Daily mean blood glucose concentrations during insulin infusion with the Glucommander and a standard paper form insulin infusion algorithm are measured every day up until 10 days and a mean values of these levels are calculated. The Mean blood glucose concentrations are measured once the target blood glucose levels are achieved after admission
Time frame: First 10 days of ICU stay
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucommander | Mean Blood Glucose (BG) in mg/dl Among Glucommander Group Compared to Standard Insulin Infusion | 103.3 mg/dl | Standard Deviation 8.8 |
| Standard Insulin Infusion | Mean Blood Glucose (BG) in mg/dl Among Glucommander Group Compared to Standard Insulin Infusion | 117.3 mg/dl | Standard Deviation 16.5 |
Secondary
Mean Hospital Length of Stay in Days Among the Glucommander Group Compared to Standard Insulin Infusion
mean number of days the patients stayed in the hospital are measured among the Glucommander group and standard insulin infusion and compared
Time frame: During the complete length of hospitalization, up to 60 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucommander | Mean Hospital Length of Stay in Days Among the Glucommander Group Compared to Standard Insulin Infusion | 23.9 days | Standard Deviation 26.3 |
| Standard Insulin Infusion | Mean Hospital Length of Stay in Days Among the Glucommander Group Compared to Standard Insulin Infusion | 17.5 days | Standard Deviation 15 |
Secondary
Mean Length of Intensive Care Unit (ICU) in Days Stay Among Glucommander Group Compared to Standard Insulin Infusion Group
Mean number of days, the patients stayed in the intensive care unit are measured among glucommander group and standard insulin infusion group.
Time frame: During ICU hospitalization, up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucommander | Mean Length of Intensive Care Unit (ICU) in Days Stay Among Glucommander Group Compared to Standard Insulin Infusion Group | 8.5 days | Standard Deviation 7.6 |
| Standard Insulin Infusion | Mean Length of Intensive Care Unit (ICU) in Days Stay Among Glucommander Group Compared to Standard Insulin Infusion Group | 13.4 days | Standard Deviation 13.8 |
Secondary
Number of Patients With Severe Hypoglycemia Episodes Among the Glucommander Group Compared to Standard Algorithm
Severe hypoglycemia is defined as the blood glucose (BG) levels lower than 40 mg/dL. The number of patients enrolled among both groups with the reports of having the BG levels lower than 40 mg/dL are recorded for duration of 10 days
Time frame: First 10 days of ICU stay
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glucommander | Number of Patients With Severe Hypoglycemia Episodes Among the Glucommander Group Compared to Standard Algorithm | 3 Participants |
| Standard Insulin Infusion | Number of Patients With Severe Hypoglycemia Episodes Among the Glucommander Group Compared to Standard Algorithm | 4 Participants |