Closed Loop Glucose Control in Intensive Care Unit (CLASSIC)

This study has been completed.
Sponsor:
Collaborators:
European Commission
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Lalantha Leelarathna, University of Cambridge
ClinicalTrials.gov Identifier:
NCT01440842
First received: September 22, 2011
Last updated: December 31, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to assess the efficacy, safety and feasibility of a computer-based control algorithm to control glucose levels in adults in intensive care unit, in comparison to standard care.


Condition Intervention Phase
Stress Hyperglycaemia
Other: Closed-loop insulin delivery
Other: Standard IV insulin infusion sliding scale
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Single-centre, Randomised Controlled Trial to Assess the Safety and Efficacy of Automated Closed-loop Blood Glucose Control in Comparison With Standard Care in Adults in Intensive Care Unit

Resource links provided by NLM:


Further study details as provided by University of Cambridge:

Primary Outcome Measures:
  • Percentage of glucose values in target range (6.0 - 8.0 mmol/l) as recorded by reference glucose measurements. [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: No ]

    Definition of Reference glucose = Blood Glucose level measured by arterial blood gas analyzer.

    During the study subjects will have the reference glucose measured every 1 hour and this is used for the calculation percentage glucose values.



Secondary Outcome Measures:
  • Percentage of glucose values in range (4.0 - 10.0 mmol/l) as recorded by reference glucose measurements. [ Time Frame: Up to 49 hours in each subject ] [ Designated as safety issue: No ]

    Definition of Reference glucose = Blood Glucose level measured by arterial blood gas analyzer.

    During the study subjects will have the reference glucose measured every 1 hour and this is used for the calculation percentage glucose values.


  • Percentage of glucose values <4.0 mmol/l and >8.0 mmol/l as recorded by reference glucose measurements. [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: No ]

    Definition of Reference glucose = Blood Glucose level measured by arterial blood gas analyzer.

    During the study subjects will have the reference glucose measured every 1 hour and this is used for the calculation percentage glucose values.


  • Percentage of glucose values > 10.0 mmol/l as recorded by reference glucose measurements. [ Time Frame: Up to 49 hours in each subject, ] [ Designated as safety issue: No ]

    Definition of Reference glucose = Blood Glucose level measured by arterial blood gas analyzer.

    During the study subjects will have the reference glucose measured every 1 hour and this is used for the calculation percentage glucose values.


  • Mean and standard deviation of reference glucose measured using arterial blood gas analyzer [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: No ]

    Definition of Reference glucose = Blood Glucose level measured by arterial blood gas analyzer. This is reported in mmol/L

    During the study subjects will have the reference glucose measured every 1 hour and this is used for the calculation of mean (mmol/L) and standard deviation which will reflect the efficasy of closed loop insulin delivery.


  • Mean and median absolute and relative difference between matched pairs of subcutaneous glucose sensor and reference plasma glucose. [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: No ]
    For a given subcutaneous glucose sensor value, difference between the sensor and the reference glucose will be calculated. Example - Reference glucose 10 mmol/L and sensor glucose 12 mmol/L, therefore absolute difference will be 2 mmol/L. Mean and median of these deviations will be reported in mmol/L. The term relative implies that data has been converted to a percentage deviation from reference glucose.

  • Time to reach target glucose [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: No ]
  • Insulin infusion rates [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: No ]
  • Frequency and magnitude of significant hypoglycaemic (< 3.0 mmol/L), severe hypoglycaemic (<2.0 mmol/L) and significant hyperglycaemic (> 15mmol/l) episodes. [ Time Frame: Up to 49 hours in each subject. ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: May 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Closed-loop (Model Predictive Control Algorithm) Other: Closed-loop insulin delivery
Intravenous infusion delivery of Actrapid insulin and dextrose, dose calculated by Model Predictive Control (MPC) algorithm, based on continuous glucose sensor readings.
Active Comparator: Open loop (Standard treatment) Other: Standard IV insulin infusion sliding scale
Standard intravenous insulin infusion sliding scale as per intensive care unit protocol.

Detailed Description:

This will be a single centre, open-label, randomised, parallel design, feasibility study conducted at Neurosciences Critical Care Unit (NCCU), Addenbrooke's hospital, Cambridge, UK. Study will aim for 24 adult subjects (12 participants in each arm of the trial) and study will last for up to 49 hours in each subject. Subjects will have a commercially available Conformité Européenne(CE) marked subcutaneous glucose sensor inserted at the start of the study. Glucose data from the sensor will be transmitted to a small bedside tablet computer, containing the algorithm which will determine insulin infusion rates aimed at maintaining glucose level between 6.0 - 8.0 mmol/L. The advice from the algorithm will be sent to the infusion pump via USB cable and insulin will be delivered intravenously. The system will also deliver intravenous glucose via a second infusion pump at times of low glucose levels. Samples for reference glucose values will be obtained either from an arterial line or central venous cannula and will be analysed using standard blood gas analyser in real time. Subjects randomised to standard care will receive intravenous insulin based on current treatment guidelines at the Neurosciences critical care unit (NCCU), Addenbrooke's Hospital, Cambridge, UK.

The primary outcome is time spent in target glucose range between 6.0 to 8.0 mmol/L as recorded by reference glucose. Secondary outcomes are the time spent with glucose levels above and below target, as recorded by reference glucose, and sensor accuracy. Safety includes evaluation of significant hypoglycaemia and hyperglycaemia and other adverse events.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 18 years and older
  • Admitted to Neurosciences critical care unit; (all patients are eligible regardless of admitting diagnosis except where specified under exclusion criteria)
  • Stay in intensive care unit expected to be at least 48 hours
  • At least one of the following conditions applies:
  • Not on insulin infusion and single confirmed reference blood glucose level > 10.0 mmol/l
  • Already on insulin infusion including those subjects with pre-existing diabetes.

Exclusion Criteria:

  • Patients with diabetic ketoacidosis or hyperosmolar hyperglycaemic non-ketotic coma (HONK)
  • Patients who are receiving therapeutic hypothermia
  • Known or suspected allergy to insulin
  • Any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the patient (i.e. liver failure, other fatal organ failures)
  • Patients with significant abnormalities of blood clotting.
  • Moribund patients likely to die within 48 hours
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440842

Locations
United Kingdom
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Sponsors and Collaborators
University of Cambridge
European Commission
Cambridge University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Roman Hovorka, BSc MSc PhD University of Cambridge
Principal Investigator: Rowan Burnstein, MBBS FRCA PhD Addenbrooke's Hospital, Cambridge, United Kingdom
  More Information

No publications provided

Responsible Party: Lalantha Leelarathna, Clinical Research Associate, University of Cambridge
ClinicalTrials.gov Identifier: NCT01440842     History of Changes
Other Study ID Numbers: CLASSIC 01
Study First Received: September 22, 2011
Last Updated: December 31, 2012
Health Authority: United Kingdom: Research & Development Department, Cambridge University Hospitals NHS Foundation Trust, Box 277, Addenbrookes Hospital, Hills Road, Cambridge Cb2 0QQ AND Research Office, Univerity of Cambridge, Box 111,Addenbrookes Hospital, Hills Road,

Keywords provided by University of Cambridge:
Stress hyperglycaemia

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014