Stress HyperglycaemiaPhase 2CLASSICNCT01440842
Closed Loop Glucose Control in Intensive Care Unit
A Phase 2 study testing Closed-loop insulin delivery and Standard IV insulin infusion sliding scale in people with Stress Hyperglycaemia, run by University of Cambridge at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stress Hyperglycaemia
- What is being tested?
- Closed-loop insulin delivery and Standard IV insulin infusion sliding scale
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2012to Oct 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
Cambridge, Cambridgeshire, CB2 0QQ
About this study
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
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.
Read the 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.
- Conditions
- Stress Hyperglycaemia
- Being tested
- Closed-loop insulin delivery, Standard IV insulin infusion sliding scale
- Keywords
- Stress hyperglycaemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-loop insulin deliveryOther
Intravenous infusion delivery of Actrapid insulin and dextrose, dose calculated by Model Predictive Control (MPC) algorithm, based on continuous glucose sensor readings.
Standard IV insulin infusion sliding scaleOther
Standard intravenous insulin infusion sliding scale as per intensive care unit protocol.
| Study group | Role | What they receive |
|---|---|---|
| Closed-loop (Model Predictive Control Algorithm) | Experimental | Not described Receives: Other: Closed-loop insulin delivery |
| Open loop (Standard treatment) | Active comparator | Not described Receives: Other: Standard IV insulin infusion sliding scale |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of glucose values in target range (6.0 - 8.0 mmol/l) as recorded by reference glucose measurements.
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.
Measured: Up to 49 hours in each subject.
Secondary outcomes (8)
Percentage of glucose values in range (4.0 - 10.0 mmol/l) as recorded by reference glucose measurements.
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.
Measured: Up to 49 hours in each subject
Percentage of glucose values <4.0 mmol/l and >8.0 mmol/l as recorded by reference glucose measurements.
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.
Measured: Up to 49 hours in each subject.
Percentage of glucose values > 10.0 mmol/l as recorded by reference glucose measurements.
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.
Measured: Up to 49 hours in each subject,
Mean and standard deviation of reference glucose measured using arterial blood gas analyzer
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.
Measured: Up to 49 hours in each subject.
Mean and median absolute and relative difference between matched pairs of subcutaneous glucose sensor and reference plasma glucose.
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.
Measured: Up to 49 hours in each subject.
Time to reach target glucose
Measured: Up to 49 hours in each subject.
Insulin infusion rates
Measured: Up to 49 hours in each subject.
Frequency and magnitude of significant hypoglycaemic (< 3.0 mmol/L), severe hypoglycaemic (<2.0 mmol/L) and significant hyperglycaemic (> 15mmol/l) episodes.
Measured: Up to 49 hours in each subject.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2011 (estimated)
- Study startMay 2012
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stress HyperglycaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission, Cambridge University Hospitals NHS Foundation Trust
- Responsible party
- Principal investigator, Lalantha Leelarathna, University of Cambridge
- Investigators
- Roman Hovorka, BSc MSc PhD, Principal investigator, University of CambridgeRowan Burnstein, MBBS FRCA PhD, Principal investigator, Addenbrooke's Hospital, Cambridge, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01440842
- Sponsor's protocol ID
- CLASSIC 01
- Acronym
- CLASSIC
- Status last verified
- Dec 2012
- First submitted
- 22 Sep 2011
- Last updated
- 3 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23883613
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01440842
- Acronym / sponsor ID
- CLASSIC / CLASSIC 01
- Conditions
- Stress Hyperglycaemia
- Keywords
- Stress hyperglycaemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- European Commission, Cambridge University Hospitals NHS Foundation Trust
- Study start
- May 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 27 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Closed-loop (Model Predictive Control Algorithm) | Experimental | Other: Closed-loop insulin delivery |
| Open loop (Standard treatment) | Active comparator | Other: Standard IV insulin infusion sliding scale |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Closed-loop insulin deliveryIntravenous infusion delivery of Actrapid insulin and dextrose, dose calculated by Model Predictive Control (MPC) algorithm, based on continuous glucose sensor readings. | Other | Closed-loop (Model Predictive Control Algorithm) |
| Standard IV insulin infusion sliding scaleStandard intravenous insulin infusion sliding scale as per intensive care unit protocol. | Other | Open loop (Standard treatment) |
Primary outcome
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.
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.
8 secondary outcomes
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
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.
Percentage of glucose values > 10.0 mmol/l as recorded by reference glucose measurements.
Time frame: Up to 49 hours in each subject,
Mean and standard deviation of reference glucose measured using arterial blood gas analyzer
Time frame: Up to 49 hours in each subject.
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.
Time to reach target glucose
Time frame: Up to 49 hours in each subject.
Insulin infusion rates
Time frame: Up to 49 hours in each subject.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2013.
- Derived from this study: PubMed 23883613Leelarathna 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman Hovorka, BSc MSc PhD principal investigator
University of Cambridge
Rowan Burnstein, MBBS FRCA PhD principal investigator
Addenbrooke's Hospital, Cambridge, United Kingdom
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Closed-loop insulin delivery and Standard IV insulin infusion sliding scale in people with Stress Hyperglycaemia, run by University of Cambridge at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01440842, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2013.