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

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)

Study Overview

• Status: Completed
• Conditions: Hyperglycemias
• Intervention / Treatment: Drug: Novorapid ®, Novo Nordisk, Denmark

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.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Baselstadt
    • Basel, Baselstadt, Switzerland, 4031
      • Division of Endocrinology, Diabetes & Clinical Nutrition, Dept of Internal Medicine,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Novorapid ®, Novo Nordisk, Denmark; Comparison of a sliding scale with an intensive s.c. scale; Other Names: Novolog; insulin aspart,
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.	Drug: Novorapid ®, Novo Nordisk, Denmark; Comparison of a sliding scale with an intensive s.c. scale; Other Names: Novolog; insulin aspart,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	48 h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	24 h
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)	during observation of 48 hours
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)	during observation of 48 hours
Frequency of Hypokalaemia	Number of participants with hypokalaemia (potassium < 3.6 mmol/l, safety endpoint, expected to be similar in the two groups)	during observation of 48 hours

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Ulrich Keller, MD, Prof, Division of Endocrinology, Diabetes & Clinical Nutrition, Dept of Internal Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: July 17, 2006
• First Submitted That Met QC Criteria: July 17, 2006
• First Posted (Estimate): July 18, 2006

Study Record Updates

• Last Update Posted (Estimate): May 18, 2012
• Last Update Submitted That Met QC Criteria: May 10, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Hyperglycaemia; emergency; algorithm; s.c. insulin therapy; Emergency patient
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease Attributes; Hyperglycemia; Emergencies; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Aspart
• Other Study ID Numbers: EKBB13/06; ISRCTN55224894 (Registry Identifier: Current Controlled Trials Database)