Impact of 2 Blood Glucose Levels on Hospital Mortality in Patients Admitted in ICU (INSUREA)

Multicentre Randomized Trial Assessing the Impact of Maintaining 2 Blood Glucose Levels on Hospital Mortality in Patients Admitted to the ICU (INSUREA STUDY)

During hospitalization in the intensive care unit (ICU), the occurrence of a blood glucose imbalance is frequent and associated with increased mortality. These observations have resulted in the hypothesis that intensive insulin therapy designed to control blood glucose would improve the prognosis of patients admitted into the ICU. In a prospective, randomized, single center study in a surgical ICU during which the majority of patients had undergone cardiac surgery, intensive insulin therapy with the objective to maintain glycemia below 110 mg/dl (6.1 mmol/L) provided a significant reduction in ICU mortality and hospital mortality compared to a group with a glycemic objective of 200 mg/dl.

In a recent published article, the beneficial effect of intensive insulin therapy seems less obvious in a randomized single center study in a medical ICU. One of the potential factors limiting the impact of a therapeutic strategy like this one is the absence of achieving strict glycemic control for all patients on intensive insulin therapy. Additionally, the implementation of such a therapeutic strategy results in an increased risk of hypoglycemia, the consequences of which on morbidity remain unclear.

The aim of our study is to determine, in a mixed population of medical and surgical patients admitted to the ICU, requiring artificial ventilation with a expected duration above 48 hours, the impact of effective strict glycemic control (<6,1 mmol/l) compared to a conventional glycemic control (<11mmol/l) on hospital mortality.

Study Overview

• Status: Unknown
• Conditions: Hyperglycemia; Critically Ill Patients
• Intervention / Treatment: Other: Conventional glycemic control; Other: Strict glycemic control

Detailed Description

In both randomization arms, continuous insulin infusion will be used via the venous route of administration. Rapid action insulin Novorapid HM (Novo Nordisk, Copenhagen, Denmark) will be used.

ICU patient management requires many intravenously administered treatments in a limited number of venous lines (catecholamines, sedation, feeding, vascular filling, antiotics…). This situation does not enable to dedicate an infusion line for the intravenous administration of insulin. Despite continuous administration of insulin infusion, the concomitant administration of other treatments in the same infusion line obviously leads to significant variations in the flow of insulin actually delivered, which can lead to variations in blood glucose and adjustments secondary to the inappropriate dose of insulin. To limit this phenomenon, an OCTOPUS (Vygon, Ecouen, France) type infusion connector will be added. The infusion connector is made of 2 infusion lines one of which will be exclusively dedicated to insulin therapy subsequently limiting the risk of variations in insulin administration flow.

The determination of the number of subjects to include was carried out by using a 45% hospital mortality hypothesis in the conventional glycemic control group. and a 32 % hospital mortality hypothesis in the strict glycemic control group.

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Evry, France, 91014 Cedex
    • Not yet recruiting
    • Medico-surgical ICU Louise Michel Hospital
    • Contact: Andry Van de Louw, MD; Email: andry.vandelouw@ch-sud-francilien.fr
    • Principal Investigator: Andry Van de Louw, MD
  • Poissy, France, 78300
    • Recruiting
    • Medico-surgical ICU Poissy Saint Germain Hospital
    • Contact: Jean-Claude Lacherade, MD; Phone Number: 33 1 39 27 54 55; Email: jclacherade@chi-poissy-st-germain.fr
    • Principal Investigator: Jean-Claude Lacherade, MD

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:

• over 18 years of age
• requiring mechanical ventilation with an expected duration above 48 hours

Exclusion Criteria:

• admission for cardiac arrest
• admission for an attempt of drug autolysis or acute drunkenness
• admission for hyperosmolar and/or ketoacidosis coma
• admission for massive cerebral hemorrhage
• admission from an another ICU
• admission after surgery without any other organ failure than respiratory support (with FiO2 below 50% and PeeP below 5cm H2O)
• inclusion in an another interventional study
• patient or next of kind refusal of study participation
• pregnant women

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: B; Continuous intravenous insulin treatment (NOVORAPID) according to an algorithm to maintain glucose level at 11 mmol/L	Other: Conventional glycemic control; Continuous intravenous insulin treatment (NOVORAPID) according to an algorithm to maintain glucose level at 11 mmol/L
Experimental: A; Continuous intravenous insulin treatment (NOVORAPID) according to an algorithm to maintain glucose level below 6.1 mmol/L	Other: Strict glycemic control; Continuous intravenous insulin treatment (NOVORAPID) according to an algorithm to maintain glucose level below 6.1 mmol/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hospital mortality	Length of hospital stay

Secondary Outcome Measures

Outcome Measure	Time Frame
incidence of severe hypoglycemia (below 2.2 mmol/l)	lenght of insulin administration in ICU
ICU mortality	Length of ICU stay
Quality of obtained glycemic control in the 2 arms of the study	Length of Continuous Insulin treatment
Incidence of neuromyopathy in the ICU	Length of ICU stay

Collaborators and Investigators

• Sponsor: Poissy-Saint Germain Hospital
• Investigators: Principal Investigator: Jean-Claude Lacherade, MD, Medico-surgical ICU Poissy Saint Germain Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): September 1, 2010
• Study Completion (Anticipated): September 1, 2010

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: January 10, 2008
• First Posted (Estimate): January 11, 2008

Study Record Updates

• Last Update Posted (Estimate): February 14, 2008
• Last Update Submitted That Met QC Criteria: February 13, 2008
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: mechanical ventilation; hypoglycemia; intensive care; hyperglycemia; insulin treatment; critically ill patients
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease Attributes; Hyperglycemia; Critical Illness
• Other Study ID Numbers: 432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No