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Trial registered on ANZCTR


Registration number
ACTRN12615001379505
Ethics application status
Approved
Date submitted
18/11/2015
Date registered
17/12/2015
Date last updated
15/10/2019
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
10/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluating new guidelines based on high-sensitivity troponin for those presenting to the emergency department with suspected acute coronary syndrome (ACS)
Scientific title
Rapid Assessment of Possible ACS In the emergency Department with high sensitivity Troponin T (RAPID-TnT): Improving Decision-Making in the Face of Uncertainty: A randomised trial of 0/1 hour high-sensitivity troponin in the investigation of suspected ACS
Secondary ID [1] 287993 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
RAPID-TnT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chest Pain 296795 0
Myocardial Infarction 296872 0
Heart attack 296873 0
Condition category
Condition code
Cardiovascular 297025 297025 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention Arm: High-sensitivity/1-hour protocol.
Consenting participants will have a baseline troponin T taken upon ED arrival and a repeat sample taken 1 hour later. Both samples will be reported in high sensitivity and a disposition will be provided based on these results as follows:
Rule-out: baseline troponin less than 5ng/L if greater than 3 hour from the onset of symptoms OR baseline troponin equal to or less than 12ng/L with a change in troponin over 1 hour of less than 3ng/L: discharge to primary care with instructions regarding repeat episodes of chest pain and primary prevention advice.
Rule-in: baseline troponin equal to or greater than 52ng/L OR a change over 1 hour of equal to or greater than 5ng/L: Admit to cardiology unit for ruling in as MI.
Observe: baseline troponin between 13-51 ng/L OR a change in troponin over 1 hour of 3-4ng/L will be admitted to an inpatient or extended emergency care unit.

Functional testing at clinician discretion with consideration of current statewide ED chest pain pathways and NICE guideline recommendations.

Medical staff will be strongly encouraged to adhere to protocol-specified care pathways unless there is strong conflicting clinical judgement.

High sensitivity troponin T reporting now is reported to 2 decimal places. Values will be rounded to the nearest whole integer in order to determine protocol-recommended pathway.
Intervention code [1] 293270 0
Early detection / Screening
Comparator / control treatment
Control Arm: Current standard of care and conventional troponin T (c-TnT) report. Patients randomised to receive current standard of care will have their admission and discharge determined by the treating ED clinician in discussion with the relevant inpatient unit. Decisions will be based on the c-TnT result. Subsequent care including the scheduling of testing, other investigations and management will be physician determined
Control group
Active

Outcomes
Primary outcome [1] 296622 0
Composite endpoint: All-cause mortality and new myocardial infarction
Timepoint [1] 296622 0
30 days and 12 months post presentation to ED
Secondary outcome [1] 318944 0
Major secondary clinical outcomes will include:
All-cause mortality at 12 months which will be determined by hospital record review.





Timepoint [1] 318944 0
12 months post presentation to ED
Secondary outcome [2] 319159 0
New ACS at 12 months, defined as:
-New MI defined as chest discomfort associated with a rise and fall in troponin, or a new cardiac defect on imaging, consistent with the current 3rd Universal Definition.
-Unstable angina defined as chest pain/discomfort with an accelerated pattern or occurring at rest, associated with: dynamic ECG changes consistent with ischaemia;or functional testing consistent with ischaemia; and/or demonstrated coronary stenosis >70% by visual estimation.
Timepoint [2] 319159 0
12 months post presentation to ED
Secondary outcome [3] 319160 0
Cardiovascular mortality as determined by hospital record review.
Timepoint [3] 319160 0
30 days and 12 months post presentation to ED
Secondary outcome [4] 319161 0
New MI at 12 months defined as chest discomfort associated with a rise and fall in troponin, or a new cardiac defect on imaging, consistent with the current 3rd Universal Definition.
Timepoint [4] 319161 0
12 months post presentation to ED
Secondary outcome [5] 319162 0
Unplanned hospital admission as documented in a hospital discharge summary for:
-non-elective coronary revascularisation (PCI or CABG)
-cerebrovascular accidents with cerebral imaging
-atrial or ventricular arrhythmias
-congestive cardiac failure without MI
-peripheral revascularisation
Significant bleeding using the international clinical trial definitions at 30 days and 12 months from GUSTO, TIMI and ACUITY
Timepoint [5] 319162 0
30 days and 12 months post presentation to ED
Secondary outcome [6] 319163 0
Secondary clinical outcomes for health economic evaluation will include:
-Measures of in-hospital care: stress testing, echocardiography, coronary angiography, cardiac medications at discharge consistent with guidelines

Timepoint [6] 319163 0
30 days and 12 months post presentation to ED
Secondary outcome [7] 319202 0
-Health-related quality of life (EQ-5D) questionnaires to be completed by direct contact via telephone, or posted directly to participant with a return pain envelope.
Timepoint [7] 319202 0
at 30 days plus or minus 5 days; 6 and 12 months plus or minus 1 week.
Secondary outcome [8] 319203 0
-Resource utilisation over 12 months: Medicare data among consenting patients using Medicare Benefits Schedule (MBS), medication use from Pharmaceutical Benefits Schedule (PBS)and SA Health in-patient admissions from the AN-Diagnosis Related Group (DRG) version 6.
Timepoint [8] 319203 0
over the 12 month period from presentation to ED

Eligibility
Key inclusion criteria
a) Clinical features of suspected ACS as the principal cause for investigation;
b) Electrocardiogram (ECG) is interpreted as not reflecting coronary ischaemia;
c) Patient is 18 years of age or older;
d) Patient is willing to give written informed consent;
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) E.D presentation is for non-ACS reasons;
b) Patient has been transferred from another hospital;
c) Patient has re-presented to the E.D for suspected ACS within 30 days of their previous presentation to the E.D for suspected ACS;
d) Patient requires permanent dialysis
e) Patient is unable to provide their clinical history due to language or comorbidity or decreased conscious state.

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



Intervention assignment
Parallel
Other design features
This study will employ a randomised non-inferiority trial design, nested within an ongoing city-wide registry of ED patients with chest pain. The registry, using current electronic health records including cardiac investigation and pathology tests, will document current care and outcomes of patients admitted or discharged directly from ED following presentations with chest pain. Employing a prospective randomisation and open labelled blinded endpoint adjudication (PROBE) design, the trial will evaluate the effectiveness, safety and cost-effectiveness of a high-sensitivity troponin T assay guided management strategy facilitating early outpatient management among patients without objective evidence of ischaemia during the initial assessment. All other subsequent investigation and management will be left to the discretion of the clinician. Clinical events will be determined at 30 days and at 12 months.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All sample size calculations assume a Type I and II error rates of 5% and 20% respectively. For the safety analysis, direct discharge from the ED in the TRAPID-AMI study was reported in ~60% of patients. In addition, ED physicians report an “acceptable” 30-day missed death or MI rate of less than 1%. Consequently, assuming a primary end point in the active arm of 0.3% and a 60%/40% ED discharge ratio, a sample size of 1,212 ED discharged patients in the active arm and 808 ED discharged patients in the control arm (total n = 2,020) provides 80% power to demonstrate the noninferiority of hs-TnT to standard TnT, assuming a “clinically acceptable 1% absolute rate” (ie, noninferiority margin of 0.7%).

However, several other factors required further consideration in the sample size estimation for the primary analysis. First, a further 2,020 patients not discharged from the ED (ie, those 40% and 60% of patients admitted, died, and transferred) contribute to the primary analysis (total n = 4,040). Second, our previous experience has shown that 22% of patients present with a troponin =30 ng/L, and because these patients receive little difference in reporting protocols and care between study arms, this dilutes study power. Accounting for these patients and a 3% attrition rate by 12 months as previously seen, a sample size of 5,400 is planned.” Assuming a control arm event rate of 2.1% as seen in our first hs-Troponin RCT, this sample size (n=5400) and a NIM of 0.5% ( i.e. chosen to represent a number needed to harm (NNH) of no more than 200 for patients treated under the active arm) we have 80% to detect an event rate up to 1.45%. This event rate is consistent the hs-Troponin reporting arm of the prior RCT. Assuming no difference in quality of life, and a standard deviation in costs of $3000, the health economic analysis has > 90% power to detect a difference of $650 dollars per patient assessed.

Recruitment
Recruitment status
Active, not 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)
SA
Recruitment hospital [1] 4653 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 4654 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 4655 0
Noarlunga Health Service - Noarlunga Centre
Recruitment hospital [4] 4656 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [5] 4657 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 12225 0
5000 - Adelaide
Recruitment postcode(s) [2] 12226 0
5112 - Elizabeth
Recruitment postcode(s) [3] 12227 0
5042 - Bedford Park
Recruitment postcode(s) [4] 12228 0
5011 - Woodville
Recruitment postcode(s) [5] 12229 0
5168 - Noarlunga Centre

Funding & Sponsors
Funding source category [1] 292461 0
Other Collaborative groups
Name [1] 292461 0
SA Emergency Department Working Group
Address [1] 292461 0
Flinders Medical Centre
1 Flinders Drive
Bedford Park SA 5042
Country [1] 292461 0
Australia
Funding source category [2] 299474 0
Government body
Name [2] 299474 0
NHMRC
Address [2] 299474 0
Research Committee Secretariat NHMRC GPO Box 1421 Canberra ACT 2601
Country [2] 299474 0
Australia
Funding source category [3] 303246 0
Commercial sector/Industry
Name [3] 303246 0
Roche Diagnostics International
Address [3] 303246 0
Roche Diagnostics International Ltd
Forrenstrasse 2
6343 Rotkreuz
Switzerland
Country [3] 303246 0
Switzerland
Primary sponsor type
Other Collaborative groups
Name
SA Emergency Department Working Group
Address
Flinders Medical Centre
1 Flinders Drive
Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 291161 0
None
Name [1] 291161 0
None
Address [1] 291161 0
None
Country [1] 291161 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293867 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 293867 0
Flat 6
The Flats
1 Flinders Drive
Bedford Park SA 5042
Ethics committee country [1] 293867 0
Australia
Date submitted for ethics approval [1] 293867 0
19/03/2015
Approval date [1] 293867 0
08/04/2015
Ethics approval number [1] 293867 0
HREC/15/SAC/158

Summary
Brief summary
The health sciences are replete with innovations promising improvements in health care delivery and outcome. Yet their clinical application based on intuition is often imprecise, conservative and beset with biases leaving these potential gains unrealised. To translate healthcare innovations into real patient and system benefits, clinical decisions and practice must evolve in parallel, supported by objective validated evidence. One such innovation is troponin testing for suspected acute coronary syndrome in the Emergency Department (ED), the most common cardiac test undertaken in Australia. Each new generation troponin assays offer greater diagnostic differentiation, but as yet no discernible improvement in management efficiency or effectiveness has occurred. Translating improved test performance into better patient care will require a more structured approach. In all South Australian (SA) public hospitals, 5th generation troponin assays have been implemented, but reporting of results has remained at previous generation levels (conventional reporting), providing a unique opportunity to robustly evaluate the impact of test reporting on patient outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61586 0
Prof Derek Chew
Address 61586 0
Flinders Medical Centre
1 Flinders Drive
Bedford Park
SA 5042
Country 61586 0
Australia
Phone 61586 0
+61 8 8404 2001
Fax 61586 0
+61 8 8404 2150
Email 61586 0
derek.chew@flinders.edu.au
Contact person for public queries
Name 61587 0
Ms Kristina Lambrakis
Address 61587 0
Department of Cardiovascular Medicine, Flinders Medical Centre 1 Flinders Drive, Bedford Park 5042 South Australia
Country 61587 0
Australia
Phone 61587 0
+61 8 8204 5836
Fax 61587 0
Email 61587 0
Kristina.Lambrakis@sa.gov.au
Contact person for scientific queries
Name 61588 0
Prof Derek Chew
Address 61588 0
Flinders Medical Centre
1 Flinders Drive
Bedford Park
SA 5042
Country 61588 0
Australia
Phone 61588 0
+61 8 8404 2001
Fax 61588 0
Email 61588 0
derek.chew@flinders.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data may contain individual participant information that will not be readily de-identifiable. IPD sharing will be considered at a later stage.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 5323 0
Chew, D., Lambrakis, K., Blyth, A., Seshadri, A., Edmonds, M., Briffa, T., . . . Papendick, C. (2019). A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible ACS In the Emergency Department with High Sensitivity Troponin T (RAPID-TnT) Study. Circulation, 03 September 2019.

https://doi.org/10.1161/CIRCULATIONAHA.119.042891
Attachments [1] 5323 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary