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Trial registered on ANZCTR

Registration number

ACTRN12615001164583

Ethics application status

Approved

Date submitted

28/09/2015

Date registered

2/11/2015

Date last updated

23/04/2021

Date data sharing statement initially provided

27/11/2018

Date results provided

23/04/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Stress hyperglycaemia and mortality in critical illness

Scientific title

Single-centre, observational trial of stress hyperglycaemia and in-hospital mortality in adult patients admitted to intensive care

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Nil

Trial acronym

Linked study record

Health condition

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

hyperglycaemia

critical illness

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Public Health

Health service research

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Stress hyperglycaemia ratio as defined by the admission blood glucose level divided by the estimated average glycaemia. Estimated average glycaemia will be computed from the HbA1c using the formula as suggested by Nathan, D.M. et al. Diabetes Care 31, 1473–8 (2008). The patients will have routine intensive care. Bloods needed for testing (e.g. for HbA1c) are those already drawn during routine intensive care and added retrospectively if not already ordered in standard care. The patients will be followed up until hospital discharge.

Intervention code [1]

Not applicable

Comparator / control treatment

admission glucose concentration by blood sample performed as part of standard care for admission into intensive care.

Control group

Active

Outcomes

Primary outcome [1]

all-cause mortality

Timepoint [1]

in-hospital admission

Secondary outcome [1]

Composite: major adverse cardiac events, acute renal injury (by KDIGO criteria), all-cause mortality, nosocomial infection, neurological complication (stroke or transient ischaemic attack) as assessed by review of hospital records, imaging results and laboratory results.

Timepoint [1]

in-hospital admission

Secondary outcome [2]

major adverse cardiac events as assessed by review of hospital records and laboratory results.

Timepoint [2]

in-hospital admission

Secondary outcome [3]

acute renal injury (by KDIGO criteria) as assessed by review of hospital records and laboratory results.

Timepoint [3]

in-hospital admission

Secondary outcome [4]

nosocomial infection as assessed by review of hospital records and laboratory results.

Timepoint [4]

in-hospital admission

Secondary outcome [5]

neurological complication (stroke or transient ischaemic attack) as assessed by review of hospital records, laboratory results and imaging results.

Timepoint [5]

in-hospital admission

Secondary outcome [6]

length of stay as assessed by review of hospital records.

Timepoint [6]

in-hospital admission

Eligibility

Key inclusion criteria

admission to intensive care unit within study period

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

elective admissions to ICU (e.g. post-operative), glycaemia-related admission to ICU, pregnancy, major blood loss

Study design

Purpose

Screening

Duration

Cross-sectional

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

A statistician has undertaken a simulation analysis using a previous study on the stress hyperglycaemia ratio (SHR) to determine the sample size required for this study. Assuming an event rate of 15%, a sample size of 1200 subjects has 80% power to detect an independent association between SHR and mortality with an estimated odds ratio of 1.25 per 0.1 increase in SHR at the two-tailed 0.05 significance level. To ensure we have sufficient power, we will recruit 1400 subjects. We will perform univariate as well as multi-variate analyses to compare the SHR with other predictors of outcome in intensive care, including absolute glycaemia, APACHE III scores.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

27/01/2016

Actual

27/01/2016

Date of last participant enrolment

Anticipated

Actual

1/04/2017

Date of last data collection

Anticipated

Actual

1/10/2017

Sample size

Target

1400

Accrual to date

Final

1262

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Flinders Medical Centre - Bedford Park

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Level 1
16 Marcus Clarke Street
Canberra ACT 2601

Country [1]

Australia

Funding source category [2]

Other

Name [2]

Royal Australasian College of Physicians

Address [2]

145 Macquarie St, Sydney NSW 2000

Country [2]

Australia

Funding source category [3]

Commercial sector/Industry

Name [3]

Novo Nordisk Regional Diabetes Scheme

Address [3]

Novo Nordisk Pharmaceuticals Pty. Ltd.
PO Box 7586
Baulkham Hills Business Centre NSW 2153

Country [3]

Australia

Funding source category [4]

Charities/Societies/Foundations

Name [4]

FMC Foundation

Address [4]

Flinders Medical Centre Foundation
Flinders Drive
Bedford Park 5042
South Australia

Country [4]

Australia

Primary sponsor type

Individual

Name

Assoc Prof Morton Burt

Address

Southern Adelaide Diabetes and Endocrinology Services
Repatriation General Hospital
216 Daws Rd, Daw Park SA 5041

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee

Ethics committee address [1]

The Flats G5 – Rooms 3 and 4
Flinders Drive
Flinders Medical Centre, Bedford Park  SA 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/06/2015

Approval date [1]

07/08/2015

Ethics approval number [1]

AU/15/F77F18

Summary

Brief summary

Hyperglycaemia in hospitalised patients is independently associated with increased morbidity and mortality in a wide range of patient groups, including the critically ill. The association between hyperglycaemia and poor inpatient outcomes is strong in patients without diabetes. However, despite a greater elevation in plasma glucose concentration and poorer prognosis, hyperglycaemia is a weaker predictor of morbidity and mortality in patients with diabetes.

A high plasma glucose concentration in a hospitalised patient can occur because of chronic poor diabetes control and be “normal” for that patient, represent a transient physiologic response to an intercurrent illness (stress hyperglycaemia), or be a combination of the above. Stress hyperglycaemia arises because of the inflammatory and neurohormonal derangements that occur during a major illness. Therefore, stress hyperglycaemia develops in proportion to the severity of an intercurrent illness, and an association between hyperglycaemia and adverse patient outcomes will be, at least in part, a reflection of this. However, stress hyperglycaemia may also directly contribute to adverse outcomes by inducing endothelial dysfunction and oxidative stress.

The Endocrine Research Unit, Southern Adelaide Diabetes and Endocrine Services recently developed a metric for stress hyperglycaemia. Estimated average glucose concentration was calculated from glycosylated haemoglobin in 2290 patients acutely admitted to Flinders Medical Centre, Adelaide. Relative hyperglycaemia was defined by the stress hyperglycaemia ratio (SHR), calculated by dividing admission glucose by estimated average glucose. Thus, a patient with a SHR of 1.5 has an admission glucose concentration 50% higher than their average glucose over the prior 3 months.
Using data gathered from a research primarily focused on validating the use of HbA1c for diagnosis of diabetes mellitus, a multivariable analysis including glucose, SHR and other potential predictors of poor outcome (e.g age, sex, renal function), the odds ratio for in-hospital death or ICU admission per 0.1 SHR increment was 1.20 (p<0.001). In contrast, the odds ratio per one mmol/L glucose increment was 1.03 (p=0.31). In contrast to glucose, the association between diabetes and SHR was not affected by diabetic status. These data suggest that SHR is a better predictor of adverse outcomes than glucose and that SHR is associated with poor outcomes in patients with and without diabetes.
In this study, we will evaluate whether SHR is more strongly associated with in-hospital mortality in critically ill patients than absolute glucose. If true, this may create a new paradigm whereby patients in ICU are selected for glucoselowering therapy based on relative, rather than absolute, hyperglycaemia.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Morton Burt

Address

Southern Adelaide Diabetes and Endocrine Services
Repatriation General Hospital
216 Daws Road,
Daw Park, SA 5041

Country

Australia

Phone

+61882751094

Fax

[email protected]

Contact person for public queries

Name

Tien Lee

Address

Southern Adelaide Diabetes and Endocrine Services
Repatriation General Hospital
216 Daws Road,
Daw Park, SA 5041

Country

Australia

Phone

+61455982828

Fax

[email protected]

Contact person for scientific queries

Name

Tien Lee

Address

Southern Adelaide Diabetes and Endocrine Services
Repatriation General Hospital
216 Daws Road,
Daw Park, SA 5041

Country

Australia

Phone

+61455982828

Fax

[email protected]

Data sharing statement

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

Undecided

No/undecided IPD sharing reason/comment

Info collected are deidentified but due to the large amount of data collected on each patient in a single centre, it may be reidentifiable to specific patients. Ethics committee and approval will need to be sought and granted for specific requests prior to release of data.

What supporting documents are/will be available?

No Supporting Document Provided

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
Embase	Does hyperglycemia affect arginine metabolites in critically ill patients? A prospective cohort and in vitro study.	2023	https://dx.doi.org/10.1186/s13098-023-01035-8

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

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