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Trial registered on ANZCTR


Registration number
ACTRN12619001246178
Ethics application status
Approved
Date submitted
23/06/2019
Date registered
9/09/2019
Date last updated
9/09/2019
Date data sharing statement initially provided
9/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A comparison of the utility of a new cardiac biomarker, cardiac myosin-binding protein C, with the exisiting gold standard cardiac biomarker, troponin, in the early assessment of patients presenting to the Emergency Department with symptoms suspicious for heart attack.
Scientific title
The utility of cardiac myosin-binding protein C in the early triage of patients with suspected acute coronary syndromes.
Secondary ID [1] 298578 0
Nil known
Universal Trial Number (UTN)
U1111-1235-8702
Trial acronym
ULYCES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart disease 313418 0
Condition category
Condition code
Cardiovascular 311853 311853 0 0
Coronary heart disease
Emergency medicine 312408 312408 0 0
Other emergency care

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Methods/Research Plan:
Design, strategy and framework:
The ULYCES study will test the clinical utility of cMyC in a subset of ~2,000 consecutive patients who present to RPH with symptoms suspicious for ACS. It will be a prospective, quantitative, observational trial. All blood samples gathered will form an “ACS biobank” which will be used for this research study, and may be used in the future for further research into new biomarkers after appropriate human research ethics approval.

Patients will be recruited from the Royal Perth Hospital Emergency department from Monday to Friday during business hours. All patients presenting with symptoms suspicious for an acute coronary syndrome will be screened for enrolment. We aim to recruit approximately 1500-2000 patients. Based on prior data we expect it will take less than 6 months to recruit this number of patients.

Blood samples:
Blood samples will be collected at presentation to the ED (0 h) and, in patients who require serial sampling according to established treatment protocols, after 2 hours as part of routine care. These blood samples will be used by treating doctors to make decisions about their care. We will also gather an additional blood sample at 1hr after arrival in the emergency department, which will be used for research purposes only.

Baseline clinical data will be routinely collected using a standardised proforma. This will include the times of symptom onset and blood collection. The samples of participants in the ULYCES study will be ‘biobanked’ by the PathWest laboratory at Royal Perth Hospital and stored at -80oC. High sensitivity cTnI will be measured on the same samples as part of routine clinical care. cMyC will be measured on batched samples using a high-sensitivity assay developed by Millipore Sigma (Hayward, California). Residual sample will be kept for additional research studies, with appropriate ethical approval.

Intervention code [1] 314837 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320524 0
The primary outcome of this study will be the proportion of patients presenting within 2 hours of the onset of symptoms with suspected / possible NSTEACS who would have had ACS either “ruled-in” or “ruled-out” using cMyC compared with the proportion of patients who had ACS “ruled-in” or “ruled-out” using hsTnI. Discrimination power will be quantified using the area under the receiver-operating characteristics curve (AUC). Net Reclassification Improvement (NRI) will be used to measure the efficacy of cMyC compared with hsTnI.

Timepoint [1] 320524 0
30 days
Primary outcome [2] 321056 0
The primary safety outcome will be the percentage of patients who suffered a major cardiac event (composite of all cause death, MI, revascularisation and cardiac re-hospitalisation) at 30 days following discharge from hospital using hsTnI or combination of hsTnI and cMyC.
Timepoint [2] 321056 0
30 days
Secondary outcome [1] 371921 0
a) Estimated cost associated with using cMyC as a rule-in or rule-out test compared with hsTnI. This will take into account:
- length of stay in hospital
- further investigations i.e. CT scans, MPS, invasive coronary angiogram
- cost of the cMyC and hsTnI assays
Timepoint [1] 371921 0
30 days

Eligibility
Key inclusion criteria
Adult patients (greater than or equal to 18 years old), presenting to the ED of Royal Perth Hospital with symptoms suspicious of ACS; defined as >5 minutes of acute symptoms in the past 12 hours potentially caused by myocardial ischaemia, in accordance with the AHA definitions (acute chest, epigastric, neck, jaw or arm pain or discomfort or pressure without a clear non-cardiac source)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients < 18 years old; patients with an ST-elevation MI; patients with a clear non-cardiac cause of chest pain and/or no indication for troponin measurement; patients requiring hospital admission for reasons apart from chest pain (e.g. other medical problems requiring admission and investigation); Patients with ongoing symptoms requiring hospitalisation for symptom relief.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Categorical data will be presented as numbers (percentages) and continuous data as means (standard deviation) or, if skewed, medians (interquartile range). Categorical variables will be compared using the chi-square test and continuous data using student’s T-test or the Mann-Whitney U test as appropriate. The sensitivity, specificity, negative and positive predictive value for both cMyC and hsTnI will be reported in all patients and in those presenting > or =2 hours after symptom onset.

Exploratory analyses will also be performed assessing the discriminatory value of cMyC levels in patients presenting <1 hour and <90 minutes after the onset of symptoms. The ability of hsTnI and cMyC at 0h to predict an acute MI and also to rule this out and to rule out death or MI at 30 days will be compared by quantifying the under the receiver-operating characteristics curve (AUC) for each biomarker. In addition, the net reclassification indices and integrated discrimination improvement values will be calculated, based on the classification assigned (‘rule in’ or ‘rule out’ for MI) using 0h hsTnI levels. Kaplan-Meier survival curves and Cox regression analysis will be performed to assess the relative ability of 0h hsTnI and cMyC to predict 2-year survival in all patients and in those presenting > or =2 hours after symptom onset.

Recruitment
Recruitment status
Not yet 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)
WA
Recruitment hospital [1] 14081 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 26871 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 303116 0
Charities/Societies/Foundations
Name [1] 303116 0
National Heart Foundation Vanguard Grant
Address [1] 303116 0
Level 2, 850 Collins Street, Docklands VIC 3008
Country [1] 303116 0
Australia
Funding source category [2] 303117 0
Charities/Societies/Foundations
Name [2] 303117 0
Royal Perth Hospital Medical Research Foundation
Address [2] 303117 0
MRF Building
Rear 50 Murray St
Perth WA 6000
Country [2] 303117 0
Australia
Funding source category [3] 303118 0
Hospital
Name [3] 303118 0
Royal Perth Hospital
Address [3] 303118 0
Wellington St.
Perth WA 6000
Country [3] 303118 0
Australia
Primary sponsor type
Individual
Name
Cara Winnall
Address
Department of Cardiology
Royal Perth Hospital
Level 4, South Block
Wellington St.
Perth WA 6000
Country
Australia
Secondary sponsor category [1] 303114 0
None
Name [1] 303114 0
Address [1] 303114 0
Country [1] 303114 0
Other collaborator category [1] 280814 0
Individual
Name [1] 280814 0
Professor Graham Hillis
Address [1] 280814 0
Department of Cardiology
Royal Perth Hospital
Level 4, South Block
Wellington St.
Perth WA 6000
Country [1] 280814 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303669 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 303669 0
East Metropolitan Health Service Human Research Ethics Office
Royal Perth Hospital
Wellington St
Perth WA 6000
Ethics committee country [1] 303669 0
Australia
Date submitted for ethics approval [1] 303669 0
18/03/2019
Approval date [1] 303669 0
14/06/2019
Ethics approval number [1] 303669 0
RGS0000003040

Summary
Brief summary
Acute chest pain is a common reason for patients to present to an Emergency Department (ED). The majority (>75%) of these individuals are at low risk of serious complications, with only a small proportion diagnosed with an acute coronary syndrome (ACS) or other major pathology. The consequences of misdiagnosis are, however, potentially catastrophic. Thus, considerable time and resources are expended to ensure the accurate triage of such patients.
Currently, high sensitivity troponin (hsTn) is used to aid in the diagnosis of ACS. However, in patients presenting early (i.e. <2 hrs) after the onset of their symptoms, hsTn may not yet have been released in great enough quantities to be detected. This may result in a treatment delay for some patients. Recently a new biomarker, cardiac myosin-binding protein C (cMyC) has been identified that rises more rapidly than hsTn in patients with ACS.
Our aim will be to compare the utility of cMyC with hsTnI in the early assessment of low risk patients presenting to the ED with chest pain. We anticipate that because serum cMyC levels rise more quickly than hsTnI, this new assay will be most useful in patients who present soon after the onset of symptoms.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94438 0
Dr Cara Winnall
Address 94438 0
Department of Cardiology
Royal Perth Hospital
Level 4, South Block
Wellington St
Perth WA 6000
Country 94438 0
Australia
Phone 94438 0
+61892242244
Fax 94438 0
Email 94438 0
Cara.Winnall@health.wa.gov.au
Contact person for public queries
Name 94439 0
Dr Cara Winnall
Address 94439 0
Department of Cardiology
Royal Perth Hospital
Level 4, South Block
Wellington St
Perth WA 6000
Country 94439 0
Australia
Phone 94439 0
+61892242244
Fax 94439 0
Email 94439 0
Cara.Winnall@health.wa.gov.au
Contact person for scientific queries
Name 94440 0
Dr Cara Winnall
Address 94440 0
Department of Cardiology
Royal Perth Hospital
Level 4, South Block
Wellington St
Perth WA 6000
Country 94440 0
Australia
Phone 94440 0
+61892242244
Fax 94440 0
Email 94440 0
Cara.Winnall@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics approval does not allow for data to be shared with third parties.
What supporting documents are/will be available?
No other documents available
Summary results
No Results