Hyperglycemias
Conditions
Keywords
Hyperglycaemia, algorithm, emergency, s.c. insulin therapy, Emergency patient
Brief summary
The aim of this study is to test the safety and efficacy of a new algorithm for intensive s.c. insulin injection in medical emergency patients with hyperglycaemia (plasma glucose concentration ≥ 8 mmol/l)
Detailed description
BACKGROUND: Prospective randomized trials have shown that near-normoglycemic blood glucose control using insulin infusions achieves a significant reduction in mortality of severely ill patients in intensive care units, of patients with acute myocardial infarction and with stroke. This implies that most severely ill patients with hyperglycemia should be treated with insulin to reach near-normoglycemia. However, this is not common practice today in emergency room admissions outside the intensive care unit, and strategies to achieve near-normoglycemia safely outside the ICU setting with s.c. injections (insulin infusions are too risky outside the ICU) have not been established. AIM: To evaluate an insulin therapy algorithm using s.c. injections which permits effective and safe glycemic management of emergency room patients with hyperglycemia. DESIGN: Randomized, controlled trial with an open intervention. Patients presenting with hyperglycemia on admission to the emergency room are randomized 1:1 either to conventional treatment (conventional insulin group) or to intensive treatment (intensive insulin group). METHODS: 140 patients admitted to the medical emergency rooms of the University Hospital Basel and the Regional Hospital of Solothurn will be included and randomized as described above. All patients with plasma glucose levels exceeding 8.0 mmol/l will be included. Exclusion criteria include severely immunocompromised patients, patients in shock, patients with terminal illnesses on palliative care, type 1 diabetes with or without ketoacidosis and patients which require intensive care unit (ICU) or cardial care unit (CCU) therapy. PRIMARY ENDPOINT: Time in the glycaemic target range (5.5-7.0 mmol/l) during the period of observation of 48 hours (expected to be longer in the intensive insulin group) SECONDARY ENDPOINTS: Time to reach the target range. Frequency of hypoglycaemia (plasma glucose \< 3.8 mmol/l). Frequency of severe hypoglycaemia (plasma glucose \< 2.5 mmol/l. Frequency of hypokalaemia.
Interventions
DRUGNovorapid ®, Novo Nordisk, Denmark
Comparison of a sliding scale with an intensive s.c. scale
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* all patients with hyperglycaemia (≥ 8.0 mmol/l) admitted to the medical emergency room. * patients with presumed hospitalisation in ER or medical ward of more than 48 h duration.
Exclusion criteria
* patients in shock (defined as hypotension or shock index \> 1 with oliguria, changed mental status and metabolic acidosis) * patients with a terminal illness on palliative care * patients with type 1 diabetes * patients with insulin pump therapy * patients with need for hospitalisation in the intensive or coronary care unit. * patients with presumed hospitalisation shorter than 48 hours * known pregnancy (in women with childbearing potential pregnancy test for exclusion mandatory) * no informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in the Glycaemic Target Range (5.5-7.0 mmol/l) During the Period of Observation of 48 Hours | 48 h | Hours in which the plasma glucose was between 5.5 and 7.0 mmol/l (expected to be longer in the intensive insulin group) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach the Target Range | 24 h | Hours needed to reach 5.5.-7.0 mmol/l (expected to be shorter in the intensive insulin group). |
| Frequency of Hypoglycemia | during observation of 48 hours | absolute number of participants with hypoglycemia (plasma glucose \< 3.8 mmol/l) (safety endpoint, expected to be similar in the two groups) |
| Frequency of Severe Hypoglycaemia | during observation of 48 hours | Number of participants with severe hypoglycaemia (plasma glucose \< 2.5 mmol/l) (safety endpoint, expected to be similar in the two groups) |
| Frequency of Hypokalaemia | during observation of 48 hours | Number of participants with hypokalaemia (potassium \< 3.6 mmol/l, safety endpoint, expected to be similar in the two groups) |
Countries
Switzerland
Participant flow
Recruitment details
Recruitment Basel 22.01.2007 until 31.08.2008 Recruitment Solothurn 30.12.2006-29.04.2010
Participants by arm
| Arm | Count |
|---|---|
| Conventional Insulin Group In the conventional insulin group only the meal-glucose adapted sliding scale at beginning is pre-determined. All adaptations of the insulin sliding scale remain upon the discretion of the treating physician. | 63 |
| Intensive Insulin Therapy Algorithm The algorithm in the intensive insulin group contains four insulin resistance factors, depending on baseline features of the patients and on the changes of plasma glucose levels after insulin administration. Every two to four hours the plasma glucose level is measured and Insulin aspart (Novorapid®) is injected s.c. according to the scheme. If the patient is eating, the dose of Insulin aspart (NovoRapid®)is increased according to the amount of carbohydrate intake. | 67 |
| Total | 130 |
Baseline characteristics
| Characteristic | Intensive Insulin Therapy Algorithm | Conventional Insulin Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 52 Participants | 52 Participants | 104 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 11 Participants | 26 Participants |
| Age Continuous | 72.43 years STANDARD_DEVIATION 11.67 | 74.22 years STANDARD_DEVIATION 8.77 | 73.30 years STANDARD_DEVIATION 10.33 |
| Region of Enrollment Switzerland | 67 participants | 63 participants | 130 participants |
| Sex: Female, Male Female | 29 Participants | 34 Participants | 63 Participants |
| Sex: Female, Male Male | 38 Participants | 29 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 63 | 26 / 67 |
| serious Total, serious adverse events | 0 / 63 | 0 / 67 |
Outcome results
Primary
Time in the Glycaemic Target Range (5.5-7.0 mmol/l) During the Period of Observation of 48 Hours
Hours in which the plasma glucose was between 5.5 and 7.0 mmol/l (expected to be longer in the intensive insulin group)
Time frame: 48 h
Population: Intension to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Insulin Group | Time in the Glycaemic Target Range (5.5-7.0 mmol/l) During the Period of Observation of 48 Hours | 13.0 hours | Standard Deviation 14.7 |
| Intensive Insulin Therapy Algorithm | Time in the Glycaemic Target Range (5.5-7.0 mmol/l) During the Period of Observation of 48 Hours | 22.5 hours | Standard Deviation 10.5 |
Secondary
Frequency of Hypoglycemia
absolute number of participants with hypoglycemia (plasma glucose \< 3.8 mmol/l) (safety endpoint, expected to be similar in the two groups)
Time frame: during observation of 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Insulin Group | Frequency of Hypoglycemia | 4 participants |
| Intensive Insulin Therapy Algorithm | Frequency of Hypoglycemia | 13 participants |
Secondary
Frequency of Hypokalaemia
Number of participants with hypokalaemia (potassium \< 3.6 mmol/l, safety endpoint, expected to be similar in the two groups)
Time frame: during observation of 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Insulin Group | Frequency of Hypokalaemia | 15 participants |
| Intensive Insulin Therapy Algorithm | Frequency of Hypokalaemia | 15 participants |
Secondary
Frequency of Severe Hypoglycaemia
Number of participants with severe hypoglycaemia (plasma glucose \< 2.5 mmol/l) (safety endpoint, expected to be similar in the two groups)
Time frame: during observation of 48 hours
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Conventional Insulin Group | Frequency of Severe Hypoglycaemia | 0 participants | 0 |
| Intensive Insulin Therapy Algorithm | Frequency of Severe Hypoglycaemia | 1 participants | 0 |
Secondary
Time to Reach the Target Range
Hours needed to reach 5.5.-7.0 mmol/l (expected to be shorter in the intensive insulin group).
Time frame: 24 h
Population: Intension to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Insulin Group | Time to Reach the Target Range | 24.3 hours | Standard Deviation 18.4 |
| Intensive Insulin Therapy Algorithm | Time to Reach the Target Range | 11.8 hours | Standard Deviation 9.4 |