Evaluation of an Algorithm for Intensive s.c. Insulin Therapy in Emergency Room Patients With Hyperglycaemia

• 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)

• Time to Reach the Target Range [ Time Frame: 24 h ] [ Designated as safety issue: No ]
  Hours needed to reach 5.5.-7.0 mmol/l (expected to be shorter in the intensive insulin group).
• Frequency of Hypoglycemia [ Time Frame: during observation of 48 hours ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: during observation of 48 hours ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: during observation of 48 hours ] [ Designated as safety issue: Yes ]
  Number of participants with hypokalaemia (potassium < 3.6 mmol/l, safety endpoint, expected to be similar in the two groups)

• Time to reach the target range (expected to be shorter in the intensive insulin group).
• Frequency of hypoglycaemia (plasma glucose < 3.8 mmol/l) (safety endpoint, expected to be similar in the two groups)
• Frequency of severe hypoglycaemia (plasma glucose < 2.5 mmol/l) (safety endpoint, expected to be similar in the two groups)
• Frequency of hypokalaemia (safety endpoint, expected to be similar in the two groups)

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)

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.

• Active Comparator: 1

  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.

  Intervention: Drug: Novorapid ®, Novo Nordisk, Denmark
• Experimental: 2

  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.

  Intervention: Drug: Novorapid ®, Novo Nordisk, Denmark

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