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Trial registered on ANZCTR


Registration number
ACTRN12616001135404
Ethics application status
Approved
Date submitted
2/08/2016
Date registered
19/08/2016
Date last updated
16/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Liberal blood glucose control in critically ill patients with pre-existing type 2 diabetes.
Scientific title
Liberal glUcose Control in critically Ill patients with pre-existing type 2 Diabetes (LUCID): a phase II multicentre randomised controlled trial to evaluate the prevalence and effect of hypoglycaemia.
Secondary ID [1] 289830 0
NA
Universal Trial Number (UTN)
Trial acronym
LUCID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 299758 0
Critical illness 299789 0
Condition category
Condition code
Metabolic and Endocrine 299691 299691 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will be delivered by an ICU nurse, the insulin will be commenced when blood glucose > 14.0 mmol/L and infusion adjusted to target blood glucose 10-14 mmo/L. Concentrations < 10 mmol/L would not be actively treated with glucose. As per the NICE-SUGAR trial each ICU will be able to use the relevant institutional protocol rather than a standardised protocol.
Treatment will be for the duration of ICU admission until day 28.
Study data will be collected by the sites research nurse and each site will have a monitoring visit to ensure accurate data collection.
Intervention code [1] 295508 0
Treatment: Other
Intervention code [2] 295533 0
Treatment: Drugs
Comparator / control treatment
The control will be ‘standard care’ which is the commencement of insulin when blood glucose is > 10.0 mmol/L, with insulin adjusted to target blood concentrations in the range 6-10 mmol/L.
Again insulin algorithms will be via local protocol rather than standardised within the study.
Control group
Active

Outcomes
Primary outcome [1] 299152 0
Incident hypoglycaemia (defined as a blood glucose reading < 4.0 mmol/L) during ICU admission.
Timepoint [1] 299152 0
During ICU admission up to and including day 28.
Secondary outcome [1] 326342 0
We will report severity of hypoglycaemia from clinically recorded point of care testing.
Timepoint [1] 326342 0
During ICU admission up to and including day 28.
Secondary outcome [2] 326423 0
We will report frequency of hypoglycaemia (defined as a new blood glucose < 4.0 mmol/L recorded without a blood glucose < 4.0 mmol/L recorded in the previous 4 hours) from clinically recorded point of care testing.
Timepoint [2] 326423 0
During ICU admission up to and including day 28
Secondary outcome [3] 326428 0
We will report relative hypoglycaemia (defined as > 30% drop from premorbid estimated average glucose, which will be calculated by the formula estimated average glucose (mmol/L) = 1.59 X HbA1c (%) - 2.59)
Timepoint [3] 326428 0
During ICU admission up to and including day 28.
Secondary outcome [4] 326429 0
We will report glycaemic variability (both coefficient of variability and standard deviation for each patient). \
The precise frequency of blood glucose measurement will be determined by local practice but be no less than every four hours and we will record whether measurement is via blood gas analyser or point of care glucometry.
Timepoint [4] 326429 0
During ICU admission up to and including day 28.
Secondary outcome [5] 326430 0
We will report time-weighted mean glucose.
The precise frequency of blood glucose measurement will be determined by local practice but be no less than every four hours and we will record whether measurement is via blood gas analyser or point of care glucometry.
Timepoint [5] 326430 0
During ICU admission up to and including day 28.
Secondary outcome [6] 326431 0
We will report drop from peak glucose > 30%. Premorbid estimated average glucose will be calculated by the formula estimated average glucose (mmol/L) = 1.59 X HbA1c (%) - 2.59)
Timepoint [6] 326431 0
During ICU admission up to and including day 28
Secondary outcome [7] 326432 0
We will report patients measurement of HbA1c (2ml). HbA1c will be measured using high performance liquid chromatography at each site.
Timepoint [7] 326432 0
On recruitment in to the study.
Secondary outcome [8] 326439 0
90 day all-cause mortality
Timepoint [8] 326439 0
at 90 days
Secondary outcome [9] 326440 0
Number of days alive and not in hospital censored at 90 days
Timepoint [9] 326440 0
at 90 days
Secondary outcome [10] 326441 0
Percentage of patients with positive blood cultures to day 28
Timepoint [10] 326441 0
at day 28
Secondary outcome [11] 326442 0
ICU and hospital discharge status
Timepoint [11] 326442 0
at day 90
Secondary outcome [12] 326443 0
Results ofEQ-5DL quality of life survey
Timepoint [12] 326443 0
performed at day 90

Eligibility
Key inclusion criteria
Inclusion:
Adult patients (aged 18 years or older).
Expected to remain in the ICU until the day after tomorrow.
Patient has either an arterial or central line in situ, or the placement of an arterial or central line is imminent (within the next hour) as part of routine ICU management.
Patient has type 2 diabetes.
The treating clinician believes that that there is a reasonable likelihood that a blood glucose concentration greater than 10 mmol/L will be recorded at some stage during the ICU admission.
The treating clinician has equipoise that targeting glucose concentrations below or above 10.0 mmol/L are equally appropriate.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Death during ICU admission is deemed to be inevitable.
Admitted to the ICU for treatment of diabetic ketoacidosis or hyperosmolar state.
Patients who have juvenile type 1 diabetes.
Patients not prescribed glucose-lowering drug treatment (oral or subcutaneous) prior to index hospital admission.
Patients expected to be eating before the end of the day.
Patients who have previously suffered hypoglycemia without documented full neurological recovery.
When there is documented evidence that the patient has no legal surrogate decision maker, and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent.
Patient has been in the study ICU or another ICU for greater than 24 h during the index admission.
Enrolment not considered in the patient’s best interests.
Patient has previously been enrolled in LUCID.
Females who are pregnant or suspected to be pregnant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be allocated to either arm of the study using a permuted block randomisation method of variable block sizes, stratified by site. Central randomisation will be performed using a secure, web-based, randomisation interface. Randomisation will not be performed until participants fulfil all eligibility criteria and are ready to be assigned to study treatment. While treatment cannot be blinded, study participants will be blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Central randomisation will be performed using a secure, web-based, randomisation interface
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analysis will be performed by a statistician. Data will be presented as n (95% CI), mean (SD) or median [IQR] as appropriate. The main analyses will be conducted on an intention to treat basis using standard statistical methods for categorical and continuous data. We will report the primary outcome (incident hypoglycaemia) as relative risk and 95% confidence intervals. Demographic and time weighted glucose data will be analyzed using independent samples t-tests, Chi-square, Fisher’s exact and Mann-Whitney tests as appropriate. We will report mortality data at day 90 and the number of days alive and not in hospital censored at 90 days. These data will be analysed using Kaplan-Meier analyses and log-rank tests. Percentage of patients with positive blood cultures will be analysed using Chi-square test. A detailed statistical analysis plan will be prepared and published before database lock.
Our sample size is based on pilot data from our exploratory study at the Royal Adelaide Hospital with the relative risk of hypoglycaemia (liberal vs. control: 0.47 (95% CI, 0.19-1.13). Assuming a baseline event rate from NICE-SUGAR data of incident hypoglycaemia in participants with type 2 diabetes assigned to conventional treatment of 17.5%, a sample size of 408 study participants would provide 80% power (alpha 0.05, delta 9.5%) to determine a reduction in hypoglycaemic episodes. We will allow 10% loss to follow up/unexpected short period of observation so that we will enrol 450 participants.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,VIC
Recruitment hospital [1] 6358 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 6359 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 6360 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 6361 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 6362 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 6363 0
Alice Springs Hospital - Alice Springs
Recruitment hospital [7] 6364 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [8] 6365 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [9] 6366 0
Western Private Hospital - Footscray
Recruitment hospital [10] 6367 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 13908 0
5000 - Adelaide
Recruitment postcode(s) [2] 13909 0
3050 - Parkville
Recruitment postcode(s) [3] 13910 0
3084 - Heidelberg
Recruitment postcode(s) [4] 13911 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 13912 0
2065 - St Leonards
Recruitment postcode(s) [6] 13913 0
870 - Alice Springs
Recruitment postcode(s) [7] 13914 0
3220 - Geelong
Recruitment postcode(s) [8] 13915 0
5112 - Elizabeth Vale
Recruitment postcode(s) [9] 13916 0
3011 - Footscray
Recruitment postcode(s) [10] 13917 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 8070 0
New Zealand
State/province [1] 8070 0
Auckland

Funding & Sponsors
Funding source category [1] 294211 0
Hospital
Name [1] 294211 0
Royal Adelaide Hospital
Address [1] 294211 0
Intensive Care Unit Level 4 North wing, Royal Adelaide Hospital, North terrace, Adelaide, South Australia, 5000
Country [1] 294211 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace, Adelaide, South Australia, 5000
Country
Australia
Secondary sponsor category [1] 293060 0
None
Name [1] 293060 0
Address [1] 293060 0
Country [1] 293060 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295619 0
Royal Adelaide Hospital
Ethics committee address [1] 295619 0
North Terrace, Adelaide, South Australia, 5000
Ethics committee country [1] 295619 0
Australia
Date submitted for ethics approval [1] 295619 0
03/08/2016
Approval date [1] 295619 0
27/03/2017
Ethics approval number [1] 295619 0
HREC/16/RAH/316

Summary
Brief summary
When patients with diabetes are very unwell (critically ill and admitted to ICU) their blood glucose levels are often higher than previously. This frequently requires the use of insulin which is administered directly into a vein.
We are uncertain about how aggressively we should treat these blood glucose levels.
Currently, patients with diabetes are treated exactly like all other patients, i.e. persons without diabetes, such that insulin is administered when blood glucose reaches 10 mmol/L and titrated to target a blood glucose less than 10 mmol/L. This approach - called conventional glucose control - may increase the risk of very low blood glucose levels (termed ‘hypoglycaemia’), which is known to be harmful to patients in ICU, and may cause blood glucose levels that are low relative to their normal blood glucose levels before they were sick (termed ‘relative hypoglycaemia’), which may also be harmful.
Because intensive care clinicians are uncertain as to which of these approaches is better participants will be randomly assigned, like the flip of a coin, to receive either:
Conventional glucose control participants will be treated the same way patients with diabetes usually are, which is exactly like all other patients without diabetes, and insulin will be administered when blood glucose reaches 10 mmol/L with insulin adjusted to target blood concentrations in the range 6-10 mmol/L.
OR
Liberal glucose control participants will only have insulin administered when their blood glucose is > 14 mmol/L and the insulin will be titrated to target a blood glucose 10-14 mmol/L.
We are evaluating whether a more ‘liberal’ approach in patients with diabetes, i.e. insulin in administered when blood glucose is > 14 mmol/L and titrated to target a blood glucose 10-14 mmol/L leads to a reduction in complications that are associated with insulin use and result in better outcomes for patients with diabetes. This approach – called liberal glucose control - isn’t necessarily better, as higher blood glucose levels may increase the risk of developing infections in ICU and could lead to weakness after ICU.
This study will include 450 patients who have diabetes and are admitted to ICU. Patients admitted to one of 12 hospitals in Australia or New Zealand will be asked to participate.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 67970 0
A/Prof Adam Deane
Address 67970 0
Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria 3050
Country 67970 0
Australia
Phone 67970 0
+61882224624
Fax 67970 0
+61882222367
Email 67970 0
adam.deane@mh.org.au
Contact person for public queries
Name 67971 0
Mr Alex Poole
Address 67971 0
Intensive care unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000
Country 67971 0
Australia
Phone 67971 0
+61882224624
Fax 67971 0
Email 67971 0
Alex.Poole@sa.gov.au
Contact person for scientific queries
Name 67972 0
A/Prof Adam Deane
Address 67972 0
Intensive care unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000
Country 67972 0
Australia
Phone 67972 0
+61882224624
Fax 67972 0
Email 67972 0
Adam.m.deane@gmail.com

No information has been provided regarding IPD availability
Summary results
No Results