Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001295336
Ethics application status
Approved
Date submitted
31/08/2017
Date registered
7/09/2017
Date last updated
9/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The relationship between hospital outcomes and increased sugar levels due to illness (stress hyperglycaemia) using a new marker called the Stress Hyperglycaemia Ratio
Scientific title
Stress hyperglycaemia and hospital outcomes in acutely hospitalised patients as determined by the Stress Hyperglycaemia Ratio
Secondary ID [1] 290274 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stress hyperglycaemia 300507 0
Condition category
Condition code
Metabolic and Endocrine 300364 300364 0 0
Diabetes

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The association of stress hyperglycaemia with adverse outcomes associated with hospitalisations will be determined using admission glucose level, and the relative change in glucose at admission as determined by the Stress Hyperglycaemia Ratio. SHR is defined by glucose value closest to the time of admission divided by the estimated average glycaemia ( as calculated from the HbA1c using the formula developed by Nathan et al. Diab Care 2008;31:1473–14788. An adverse outcome is in-hospital death or the acute need for critical care, with patients being observed for the duration of the inpatient admission for the main endpoint, and up to 30 days post-discharge for the secondary endpoints. The strength of association of adverse outcomes will be compared in a multivariable model using admission glucose and admission Stress Hyperglycaemia Ratio, along with other variables known to impact outcomes.
Intervention code [1] 296071 0
Diagnosis / Prognosis
Comparator / control treatment
The association of outcomes with glucose levels will act as the conventional control group. The patient cohort will be selected from patients admitted to hospital over the period 21/1/2013 to 25/7/2017 identified using hospital casemix (ICD10) databases.
Control group
Historical

Outcomes
Primary outcome [1] 299820 0
The composite outcome of in-hospital death or the acute need for critical care from the point of hospital admission until hospital discharge, using administrative hospital data (International Code of Diseases classification).
Timepoint [1] 299820 0
The time of admission until the time of hospital discharge.
Secondary outcome [1] 328199 0
The development of new infection from the point of admission until 30 days after hospital discharge, excluding the initial primary admission diagnosis, as determined by casemix ICD10 coding and hospital records.
Timepoint [1] 328199 0
The time of admission until 30 days post-discharge.
Secondary outcome [2] 328200 0
The development of any new thrombus-related event (embolic stroke, MI, DVT, PE) from the point of admission until 30 days post-discharge, excluding the initial primary admission diagnosis as determined by casemix ICD10 coding and hospital records.
Timepoint [2] 328200 0
The time of admission until 30 days post-discharge.
Secondary outcome [3] 338601 0
In-hospital mortality as determined by hospital databases (ICD10 casemix coding).
Timepoint [3] 338601 0
The time of admission until the time of hospital discharge.
Secondary outcome [4] 338602 0
The need for critical care during hospitalisation, as identified by hospital databases (ICD10 casemix coding).
Timepoint [4] 338602 0
Time of admission to time of discharge

Eligibility
Key inclusion criteria
Inpatient admission
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
<18 years age, admissions for psychiatric illness, obstetrics, gynaecology, specific management of blood glucose eg diabetic ketoacidosis, overdose, poisoning, dialysis, non-acute admissions for respite, chemotherapy, patients requiring routine post-op care in ICU.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Retrospective
Statistical methods / analysis
Statistical power: Our previous work demonstrated a superior association between the Stress Hyperglycaemia Ratio and absolute glucose levels with a sample size of 2290 patients. The current database is expected to yield 7000 patients and will be should be well-powered to reproduce this association if it is present.
Variables of interest (glucose, SHR, age, haemoglobin, gender, renal function, ethnicity), will be subject to multivariable regression analysis to determine the association with adverse outcomes.
Locally Weighted Scatterplot Smoothing will be used to explore the relationship between patients with (HbA1c>=6.5%) or without (HbA1c<6.5%) pre-existing chronic background hyperglycaemia.
Subgroup analysis of patients with mean glucose <10mmol/L will be made to determine existence of clinically significant stress hyperglycaemia at glucose levels conventionally considered clinically insignificant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/09/2017
Actual
7/09/2017
Date of last participant enrolment
Anticipated
7/11/2017
Actual
15/02/2018
Date of last data collection
Anticipated
7/11/2017
Actual
20/07/2018
Sample size
Target
5000
Accrual to date
Final
5048
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 6778 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 14430 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 294644 0
Hospital
Name [1] 294644 0
Flinders Medical Centre
Country [1] 294644 0
Australia
Primary sponsor type
Hospital
Name
Flinders Medical Centre
Address
Flinders Drive, Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 293508 0
None
Name [1] 293508 0
Address [1] 293508 0
Country [1] 293508 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296082 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 296082 0
Flinders Medical Centre
Flinders Drive
Bedford Park, SA 5042
Ethics committee country [1] 296082 0
Australia
Date submitted for ethics approval [1] 296082 0
17/12/2016
Approval date [1] 296082 0
27/02/2017
Ethics approval number [1] 296082 0
OFR # 475.16 - HREC/16/SAC/490

Summary
Brief summary
Hyperglycaemia in hospitalised patients is independently associated with increased morbidity and mortality in a wide range of patient groups, including post-operative outcomes. The association between hyperglycaemia and poor outcomes is strong in patients without diabetes, but a weaker predictor in patients with diabetes.
This discrepancy is in part driven by the difficulty in distinguishing genuine stress hyperglycaemia from chronic high levels seen in diabetic patients. 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 inter¬current illness (stress hyperglycaemia), or be a combination of the above.
A metric for stress hyperglycaemia has been developed at Flinders Medical Centre - the Stress Hyperglycaemia Ratio is defined as glucose concentration divided by the Estimated Average Glucose concentration, which is calculated from HbA1c. This enables quantification of the relative change in hyperglycaemia eg a patient with a SHR of 1.4 has an glucose concentration 40% higher than their average glucose over the prior 3 months.
Our previous work indicated that the relative change in glucose was a better indicator of stress hyperglycaemia and more strongly associated with adverse patient outcomes than glucose. This initial work needs to be confirmed in a further population of hospitalised patients. We also aim to study some specific subgroups of interest, namely infections (both at admission and those that develop during the admission), and events related to blood clots (heart attacks, stroke, deep vein thromboses, and pulmonary emboli). This will enable us to determine those patients who might benefit most from early management of elevated glucose levels due to stress hyperglycaemia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69478 0
Mr Greg Roberts
Address 69478 0
Pharmacy Department
Flinders Medical Centre
Flinders Drive, Bedford Park, SA 5042
Country 69478 0
Australia
Phone 69478 0
+61 8 82046936
Fax 69478 0
+61 8 82046245
Email 69478 0
[email protected]
Contact person for public queries
Name 69479 0
Mr Greg Roberts
Address 69479 0
Pharmacy Department
Flinders Medical Centre
Flinders Drive, Bedford Park, SA 5042
Country 69479 0
Australia
Phone 69479 0
+61 8 82046936
Fax 69479 0
+61 8 82046245
Email 69479 0
[email protected]
Contact person for scientific queries
Name 69480 0
Mr Greg Roberts
Address 69480 0
Pharmacy Department
Flinders Medical Centre
Flinders Drive, Bedford Park, SA 5042
Country 69480 0
Australia
Phone 69480 0
+61 8 82046936
Fax 69480 0
+61 8 82046245
Email 69480 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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