ANZCTR - Registration

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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

21/12/2021

Date data sharing statement initially provided

21/12/2021

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]

Universal Trial Number (UTN)

Trial acronym

LUCID

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 2 Diabetes

Critical illness

Condition category

Condition code

Metabolic and Endocrine

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]

Treatment: Other

Intervention code [2]

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]

Incident hypoglycaemia (defined as a blood glucose reading < 4.0 mmol/L) during ICU admission.

Timepoint [1]

During ICU admission up to and including day 28.

Secondary outcome [1]

We will report severity of hypoglycaemia from clinically recorded point of care testing.

Timepoint [1]

During ICU admission up to and including day 28.

Secondary outcome [2]

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]

During ICU admission up to and including day 28

Secondary outcome [3]

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]

During ICU admission up to and including day 28.

Secondary outcome [4]

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]

During ICU admission up to and including day 28.

Secondary outcome [5]

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]

During ICU admission up to and including day 28.

Secondary outcome [6]

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]

During ICU admission up to and including day 28

Secondary outcome [7]

We will report patients measurement of HbA1c (2ml). HbA1c will be measured using high performance liquid chromatography at each site.

Timepoint [7]

On recruitment in to the study.

Secondary outcome [8]

90 day all-cause mortality

Timepoint [8]

at 90 days

Secondary outcome [9]

Number of days alive and not in hospital censored at 90 days

Timepoint [9]

at 90 days

Secondary outcome [10]

Percentage of patients with positive blood cultures to day 28

Timepoint [10]

at day 28

Secondary outcome [11]

ICU and hospital discharge status

Timepoint [11]

at day 90

Secondary outcome [12]

Results ofEQ-5DL quality of life survey

Timepoint [12]

performed at day 90

Eligibility

Key inclusion criteria

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 or equal to 10 mmol/L will be recorded at some stage during the ICU admission.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

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.
Requirement for specific blood glucose target as determined by the treating doctor, i.e. the treating clinician believes either intervention or standard care arms of LUCID would not be in the best interests of the patient
Patients expected to be eating before the end of the next calendar day.
Patients who have previously suffered hypoglycemia without documented full neurological recovery.
Patient cannot provide prior informed consent and 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 or equal to 24 h during the index admission.
Patient has previously been enrolled in LUCID.
Females who are pregnant or suspected to be pregnant determined by a positive serum or urine human chorionic gonadotropin (hCG) test.

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

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

Following the final interim data analysis, the DSMC recommended the trial be ceased.

Date of first participant enrolment

Anticipated

1/11/2016

Actual

8/05/2017

Date of last participant enrolment

Anticipated

21/12/2018

Actual

23/09/2020

Date of last data collection

Anticipated

31/12/2017

Actual

31/12/2020

Sample size

Target

450

Accrual to date

Final

436

Recruitment in Australia

Recruitment state(s)

NSW,NT,QLD,SA,VIC

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [3]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [4]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [5]

Royal North Shore Hospital - St Leonards

Recruitment hospital [6]

Alice Springs Hospital - Alice Springs

Recruitment hospital [7]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [8]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment hospital [9]

Western Private Hospital - Footscray

Recruitment hospital [10]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment postcode(s) [1]

5000 - Adelaide

Recruitment postcode(s) [2]

3050 - Parkville

Recruitment postcode(s) [3]

3084 - Heidelberg

Recruitment postcode(s) [4]

4102 - Woolloongabba

Recruitment postcode(s) [5]

2065 - St Leonards

Recruitment postcode(s) [6]

870 - Alice Springs

Recruitment postcode(s) [7]

3220 - Geelong

Recruitment postcode(s) [8]

5112 - Elizabeth Vale

Recruitment postcode(s) [9]

3011 - Footscray

Recruitment postcode(s) [10]

3065 - Fitzroy

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal Adelaide Hospital

Address [1]

Intensive Care Unit Level 4 North wing, Royal Adelaide Hospital, North terrace, Adelaide, South Australia, 5000

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Intensive Care Foundation

Address [2]

Level 2, 10 Ievers Terrace
Carlton, Victoria 3053, Australia

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

Diabetes Australia

Address [3]

Level 1, 101 Northbourne Ave, Turner ACT 2612

Country [3]

Australia

Primary sponsor type

Hospital

Name

Royal Adelaide Hospital

Address

North Terrace, Adelaide, South Australia, 5000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital

Ethics committee address [1]

North Terrace, Adelaide, South Australia, 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/08/2016

Approval date [1]

27/03/2017

Ethics approval number [1]

HREC/16/RAH/316

Ethics committee name [2]

Central Australian Human Research Ethics Committee

Ethics committee address [2]

PO Box 4066 Alice Springs NT 0871

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

07/03/2016

Approval date [2]

07/03/2016

Ethics approval number [2]

HREC-16-446

Ethics committee name [3]

the Alfred Human Research Ethics Committee

Ethics committee address [3]

55 Commercial Rd, Melbourne VIC 3004

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

26/10/2017

Approval date [3]

08/11/2017

Ethics approval number [3]

411/17

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

A/Prof Adam Deane

Address

Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria 3050

Country

Australia

Phone

+6139342 9253

Fax

[email protected]

Contact person for public queries

Name

Alex Poole

Address

Intensive care unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000

Country

Australia

Phone

+61882224624

Fax

[email protected]

Contact person for scientific queries

Name

Adam Deane

Address

Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria 3050

Country

Australia

Phone

+61882224624

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Individual participant data that underlie the results reported in this trial, after de-identification..

When will data be available (start and end dates)?

Beginning 3 months and ending 5 years following article publication..

Available to whom?

Researches who provide a methodologically sound proposal..

Available for what types of analyses?

To achieve aims in the approved proposal..

How or where can data be obtained?

Proposals should be directed to Principal investigator. To gain access, data requestors will need to sign a data access agreement. [email protected] or [email protected]

What supporting documents are/will be available?

Doc. No.	Type	Email
14501	Statistical analysis plan
14502	Study protocol	[email protected]
14503	Informed consent form	[email protected]
14504	Clinical study report	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial	2020	https://doi.org/10.51893/2020.2.oa3
Embase	The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.	2022	https://dx.doi.org/10.1164/rccm.202202-0329OC

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically