Clinical trial NCT01440842: Closed Loop Glucose Control in Intensive Care Unit
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stress Hyperglycaemia
Keywords: Stress hyperglycaemia
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: European Commission
name: Cambridge University Hospitals NHS Foundation Trust
First posted: 2011-09-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Percentage of glucose values in target range (6.0 - 8.0 mmol/l) as recorded by reference glucose measurements.
timeFrame: Up to 49 hours in each subject.
Secondary outcomes:
measure: Percentage of glucose values in range (4.0 - 10.0 mmol/l) as recorded by reference glucose measurements.
timeFrame: Up to 49 hours in each subject
measure: Percentage of glucose values <4.0 mmol/l and >8.0 mmol/l as recorded by reference glucose measurements.
timeFrame: Up to 49 hours in each subject.
measure: Percentage of glucose values > 10.0 mmol/l as recorded by reference glucose measurements.
timeFrame: Up to 49 hours in each subject,
measure: Mean and standard deviation of reference glucose measured using arterial blood gas analyzer
timeFrame: Up to 49 hours in each subject.
measure: Mean and median absolute and relative difference between matched pairs of subcutaneous glucose sensor and reference plasma glucose.
timeFrame: Up to 49 hours in each subject.
measure: Time to reach target glucose
timeFrame: Up to 49 hours in each subject.
measure: Insulin infusion rates
timeFrame: Up to 49 hours in each subject.
measure: Frequency and magnitude of significant hypoglycaemic (< 3.0 mmol/L), severe hypoglycaemic (<2.0 mmol/L) and significant hyperglycaemic (> 15mmol/l) episodes.
timeFrame: Up to 49 hours in each subject.
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
state: Cambridgeshire
Study officials:
affiliation: University of Cambridge
name: Roman Hovorka, BSc MSc PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Addenbrooke's Hospital, Cambridge, United Kingdom
name: Rowan Burnstein, MBBS FRCA PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leelarathna L, English SW, Thabit H, Caldwell K, Allen JM, Kumareswaran K, Wilinska ME, Nodale M, Mangat J, Evans ML, Burnstein R, Hovorka R. Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial. Crit Care. 2013 Jul 24;17(4):R159. doi: 10.1186/cc12838.