Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001833257
Ethics application status
Approved
Date submitted
5/11/2018
Date registered
12/11/2018
Date last updated
28/01/2024
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Limit of Detection in the Emergency Department Trial: A trial to rapidly rule out acute myocardial infarction and reduce hospital length of stay in patients presenting to the Emergency Department with chest pain.
Scientific title
Limit of Detection in the Emergency Department Trial (LEGEND): A pre-post intervention study of a clinical decision rule to rule out acute myocardial infarction and reduce hospital length of stay for patients presenting to the Emergency Department with chest pain
Secondary ID [1] 296513 0
Nil known
Universal Trial Number (UTN)
U1111-1223-2431
Trial acronym
LEGEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chest pain 310297 0
Acute myocardial infarction 310298 0
Condition category
Condition code
Cardiovascular 309029 309029 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is a new method for the assessment of patients who present to the Emergency Department with chest pain. The intervention will be implemented as standard care in the participating hospitals. It will be delivered in the Emergency Department by the Emergency clinician responsible for patient assessment and management. As soon as possible after presentation to the Emergency Department (within 2 hours of presentation), patients will receive an electrocardiogram (ECG) and will have a blood test taken. Troponin concentrations in the blood will be assessed using a high sensitivity troponin assay. Patients with normal ECG findings and who have a troponin concentration below the limit of detection (2ng/L for the Beckman assay used in this study) will be considered to be low-risk and considered for discharge from the emergency department with no further testing. Such patients will be provided with a shared decision making form that includes a pictorial representation of their 30 day risk of acute myocardial infarction. This form has been developed specifically for this study, but is based on the chest pain choices work completed in the United States (https://cdn.prod-carehubs.net/n1/56fab03a15e99046/uploads/2016/03/UPenn-Decision-Aid-1.pdf). Shared decision making will be used to determine whether the patient can be discharged or undergo further investigation. Shared decision making will involve the treating physician and patient (and potentially treating nurse) discussing the patients risk for further events and discussing further treatment options. Such options include additional testing or discharge with no further testing. For patients who are discharged, a standardised discharge summary will be sent to the patient’s primary care physician.

For patients with a troponin concentration above the limit of detection, the assessment will proceed as per standard care. Standard care differs slightly at each hospital. However, this typically includes serial troponin and ECG testing on presentation and at least 2 hours later (with some testing being up to 12 hours later). Some patients will also receive CT coronary angiography or a functional test for myocardial ischaemia (e.g., exercise stress test, myocardial perfusion scan, or stress radionuclide imaging).
Intervention code [1] 312828 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator will be standard care. This will differ slightly according to current practice at each site, However, it will include serial troponin and ECG testing on presentation and at least 2 hours later, Some patients will also receive CT coronary angiography or a functional test for myocardial ischaemia (e.g., exercise stress test, myocardial perfusion scan, or stress radionuclide imaging).

The control group will include all patients presenting to each participating hospital (expected 10,000 patients overall) after commencement of the study. At each of the sites, the intervention will be implemented at either:
The later of 1/3 of patients recruited with a troponin below the LoD (n=55) or two months after the start of pre-data collection,
The later of 1/2 of patients recruited with a troponin below the LoD (n=84) or three months after the start of pre-data collection, or
The later of 2/3 of patients recruited with a troponin below the LoD (n=111) or four months after the start of pre-data collection.

The interval will be randomly chosen for each hospital.
Control group
Historical

Outcomes
Primary outcome [1] 307991 0
Hospital length of stay for patients with troponin concentrations below the limit of detection on presentation to the Emergency Department. Hospital length of stay will be collected from hospital records
Timepoint [1] 307991 0
Length of stay will be assessed after discharge from hospital
Secondary outcome [1] 353581 0
The proportion of patients discharged from hospital within 4 hours of presentation and without a subsequent acute myocardial infarction within 30 days. This data will be collected from hospital records
Timepoint [1] 353581 0
Thirty days post presentation to the Emergency Department
Secondary outcome [2] 353582 0
A combined endpoint of all-cause mortality, new non-fatal acute myocardial infarction within 30 days, or unplanned revascularisation. This information will be obtained from hospital records
Timepoint [2] 353582 0
30 days and 6 months post presentation to the Emergency Department
Secondary outcome [3] 353583 0
Number of hospital representations from hospital records
Timepoint [3] 353583 0
6 months after presentation to the Emergency Department
Secondary outcome [4] 353584 0
Number of hospital admissions. This information will be obtained from hospital records
Timepoint [4] 353584 0
6 months after presentation to the Emergency Department
Secondary outcome [5] 353585 0
A composite endpoint of the number of cardiovascular tests performed. Cardiovascular tests include stress testing, echocardiography, coronary angiography or coronary CT angiography. This information will be obtained from hospital records and patient report
Timepoint [5] 353585 0
6 months after presentation to the Emergency Department.
Secondary outcome [6] 353586 0
Cost effectiveness. This is a composite outcome including cost data from hospital medical records, and prescribed medicare costs for outpatient tests. Cost effectiveness will also be based on a validated quality of life measure, Quality of life will be assessed using the EQ-5D.
Timepoint [6] 353586 0
6 months after presentation to the Emergency Department

Eligibility
Key inclusion criteria
Patients will be eligible for enrolment into the study if they are >=18 years old and the treating physician intends to investigate for acute myocardial infarction.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) have a clear non-AMI cause for their symptoms on presentation,
2) were transferred from another hospital, or
3) have previously been included in the study within a 6 month period.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Historical controlled trial
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
The current protocol covers seven sites. We will collect data for 6 months at each site. It is anticipated that this will equate to an average of 3000 patients per site and 30% of these with have a presentation troponin <LoD (1000 per site). The average length of stay for patients with a hs-cTn below the LoD in our institution is 19 hours. This sample size will provide >900% power to detect a 4-hour reduction in length of stay presuming a low ICC (0.01-0.05), 3 steps and 2-3 sites randomized per step. Further, 5% of patients at our institution are currently discharged in under 4 hours and observational research has indicated that 30% will be eligible for early discharge. The number of patients who would choose to be discharged immediately is unknown. However, the proposed sample size will provide >90% power to detect a difference in the proportion discharged larger than 2%.

Analyses will be conducted using generalized linear mixed models including clusters as random effects and time as a fixed effect. Such analyses adjust for clustering with hospitals.. For the primary endpoint (length of stay for patients with hscTn<LoD), the regression model will be fit with a log link and a negative binomial error distribution. The regression models will incorporate treatment group (standard care versus LEGEND), study site and time. Time is incorporated to identify whether any time-based trends in the study obscure the results. Age and gender may also be included in these analyses to increase the precision of the treatment group estimates. These analyses will enable adjusted treatment group differences (and 95% confidence interval of difference) to be reported. For the remaining outcomes, the entire cohort will be included in the analyses. These models will again incorporate time, site, treatment group (and potentially age and gender). The models will be fit using binomial, negative binomial, or gaussian error distributions where the outcome is binary, count, or continuous respectively). Missing data will be described and imputed using multiple imputation where appropriate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/08/2019
Actual
22/08/2019
Date of last participant enrolment
Anticipated
30/06/2022
Actual
30/06/2022
Date of last data collection
Anticipated
31/12/2022
Actual
31/12/2022
Sample size
Target
11000
Accrual to date
Final
11000
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 12360 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 12361 0
The Prince Charles Hospital - Chermside
Recruitment hospital [3] 12362 0
Logan Hospital - Meadowbrook
Recruitment hospital [4] 21022 0
Cairns Base Hospital - Cairns
Recruitment hospital [5] 21025 0
Townsville University Hospital - Douglas
Recruitment postcode(s) [1] 24617 0
4029 - Herston
Recruitment postcode(s) [2] 24618 0
4032 - Chermside
Recruitment postcode(s) [3] 24619 0
4131 - Meadowbrook
Recruitment postcode(s) [4] 24620 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [5] 24621 0
4131 - Loganlea
Recruitment postcode(s) [6] 24622 0
4032 - Chermside Centre
Recruitment postcode(s) [7] 35857 0
4870 - Cairns
Recruitment postcode(s) [8] 35860 0
4814 - Douglas

Funding & Sponsors
Funding source category [1] 301101 0
Government body
Name [1] 301101 0
Advance Queensland
Country [1] 301101 0
Australia
Funding source category [2] 310079 0
Government body
Name [2] 310079 0
National Heath and Medical Research Council
Country [2] 310079 0
Australia
Primary sponsor type
Individual
Name
Jaimi Greenslade
Address
Emergency and Trauma Centre, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4006
Country
Australia
Secondary sponsor category [1] 300714 0
None
Name [1] 300714 0
Address [1] 300714 0
Country [1] 300714 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301852 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 301852 0
Ethics committee country [1] 301852 0
Australia
Date submitted for ethics approval [1] 301852 0
22/08/2018
Approval date [1] 301852 0
27/09/2018
Ethics approval number [1] 301852 0
HREC/2018/QRBW/45352

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88322 0
A/Prof Jaimi Greenslade
Address 88322 0
Emergency and Trauma Centre
Royal Brisbane and Women's Hospital
Butterfield Street
Herston, QLD 4029
Country 88322 0
Australia
Phone 88322 0
+61 7 36466262
Fax 88322 0
Email 88322 0
[email protected]
Contact person for public queries
Name 88323 0
Jaimi Greenslade
Address 88323 0
Emergency and Trauma Centre
Royal Brisbane and Women's Hospital
Butterfield Street
Herston, QLD 4029
Country 88323 0
Australia
Phone 88323 0
+61 7 36466262
Fax 88323 0
Email 88323 0
[email protected]
Contact person for scientific queries
Name 88324 0
Jaimi Greenslade
Address 88324 0
Emergency and Trauma Centre
Royal Brisbane and Women's Hospital
Butterfield Street
Herston, QLD 4029
Country 88324 0
Australia
Phone 88324 0
+61 7 36466262
Fax 88324 0
Email 88324 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patient data is confidential and can not be publically released.


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
No additional documents have been identified.