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Trial registered on ANZCTR


Registration number
ACTRN12619001445167p
Ethics application status
Submitted, not yet approved
Date submitted
10/10/2019
Date registered
18/10/2019
Date last updated
18/10/2019
Date data sharing statement initially provided
18/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Biomarker-guided Management Following a Heart Attack
Scientific title
Effect of cardiac biomarker (Nt-proBNP and high sensitivity troponin) guided risk management on clinical outcomes (all-cause mortality and cardiovascular readmission) in patients in the convalescent phase following Acute Coronary Syndromes: a Randomised, Controlled Trial
Secondary ID [1] 299490 0
Nil Known
Universal Trial Number (UTN)
U1111-1238-9283
Trial acronym
BioMACS
Linked study record
No

Health condition
Health condition(s) or problem(s) studied:
Secondary prevention post-acute coronary syndromes 314724 0
Cardiovascular Disease 314725 0
Condition category
Condition code
Cardiovascular 313058 313058 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will be seen between 1 and 12 months post hospital discharge for ACS, and have a baseline assessment. The patients will have NT-proBNP and high-sensitivity troponin measured, for those patients in the intervention group if the NT-proBNP is greater than 15pmol/L or NT-proBNP less than 15pmol/L with hsTnT greater than the 99th centile then existing renin-angiotensin inhibitor and beta-blocker will be titrated to maximum tolerated dosages. No pre-specified specific individual drug will be used. The drugs to be titrated will be the medications that the patients were on when they were discharged from hospital. Example would be titration of cilazapril to 5mg/day or maximum tolerated dose and bisoprolol to 10mg/day or maximum tolerated dose (upper limits of these medications will not be exceeded)
Maximum tolerated dosages will be determined by absence of symptoms such as postural dizziness for more than 2 weeks.
Titration protocol will be to aim to double the dose of these medications every 2 weeks. Duration of the study for these medications is 24 months post-enrolment
Adherence will be discussed with the patients at every visit but other specific strategies will not be utilised in this study.
Intervention code [1] 315772 0
Treatment: Drugs
Intervention code [2] 315802 0
Treatment: Other
Comparator / control treatment
The control group patients will be those allocated to the control group after the baseline assessment and following the randomisation process. The cardiac biomarkers NT-proBNP and high sensitivity troponin will be measured but the study team and patient will be blinded to the result. The control group patients will continue to receive their usual medications but the dosages will not be titrated within the study protocol.
Control group
Active

Outcomes
Primary outcome [1] 321638 0
Composite outcome of time to first event of death from any cause or cardiovascular readmission
Clinical outcome data will be collected by linkage to the NZ national mortality and hospitalisation databases.
Timepoint [1] 321638 0
18 Months post-randomisation
Secondary outcome [1] 375690 0
Time to first cardiovascular readmission 18 months post-randomisation
Clinical outcome data will be collected by linkage to the NZ national mortality and hospitalisation databases.
Timepoint [1] 375690 0
18 months post-randomisation

Eligibility
Key inclusion criteria
Primary diagnosis of acute coronary syndrome
Age > 18yrs
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previously known left ventricular ejection fraction < 35%,
severe aortic stenosis
other life-limiting disease (life expectancy<1 year),
end-stage renal disease (eGFR < 15mL/min) or
inability to provide consent

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



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary end-point for the study will be death from any cause and CV readmission. For patients one-month post discharge from hospital for ACS, data from the ANZACS-QI Registry has demonstrated that 31% had either died or been readmitted to hospital for cardiovascular reasons within 18 months (Dr N Earle, personal communication). To estimate sample size, we have used a slightly more conservative 28% 18-month event rate in the control group. Assuming that the high risk subgroup identified by the biomarkers will be 75% of the cardiac biomarker group, it is projected that 843 patients per arm will be required to demonstrate a 23% relative risk reduction of death or CV readmission within 18 months (usual care event rate 28%, biomarker group event rate 22.1%, 80% power, 95% level of confidence). Allowing for 5% loss to follow up, 1770 patients will be recruited.
Statistical analyses will be undertaken by study statistician using the software "R".

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 outside Australia
Country [1] 21914 0
New Zealand
State/province [1] 21914 0

Funding & Sponsors
Funding source category [1] 303987 0
Government body
Name [1] 303987 0
NZ Health Research Council
Address [1] 303987 0
110 Stanley Street, Auckland, 1010
Country [1] 303987 0
New Zealand
Primary sponsor type
Individual
Name
Professor Rob Doughty
Address
University of Auckland, Park Road, Grafton, Auckland 1024, NZ
Country
New Zealand
Secondary sponsor category [1] 304159 0
None
Name [1] 304159 0
Address [1] 304159 0
Country [1] 304159 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304484 0
Health and Disability Ethics Committee
Ethics committee address [1] 304484 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 304484 0
New Zealand
Date submitted for ethics approval [1] 304484 0
28/08/2019
Approval date [1] 304484 0
Ethics approval number [1] 304484 0

Summary
Brief summary
Patients who present with a heart attack are at risk of recurrent heart events in the next few years. A simple blood test can measure whether the heart is under stress. If this blood test is elevated then the potential is for specific medications to be used to reduce the risk of further heart events. The hypothesis is that a biomarker-guided approach to risk assessment and management will reduce the risk of recurrent clinical events for people following heart attacks.
Patients will be those discharged from hospital following a heart attack within the last 1-12 months. Patients will be randomised (1:1) to either usual care group or to biomarker group. A stratified approach to patient management will be undertaken for the patients in the biomarker group, using heart biomarkers measured at the baseline visit. The “low biomarker” subgroup will be defined by NT-proBNP less than15pmol/L and hsTnT<99th centile; these patients will continue with follow up as per the usual care group. The “high biomarker” subgroup (NT-proBNP greater than 15pmol/L or NT-proBNP less than 15pmol/L with hsTnT greater than the 99th centile) will be seen for initiation/titration of ACE inhibitors/beta-blockers. Primary end point is the time to first event of death from any cause or cardiovascular readmission. The study will include 1770 patients at 3 centres in New Zealand, and follow up will be for 18 months.

Trial website
Trial related presentations / publications
Nil to date
Public notes

Contacts
Principal investigator
Name 97106 0
Prof Rob Doughty
Address 97106 0
Heart Foundation Chair of Heart Health
University of Auckland
Dept of Medicine
Park Road
Grafton
Auckland 1024
New Zealand
Country 97106 0
New Zealand
Phone 97106 0
+64 9 9239804
Fax 97106 0
+64 9 377149
Email 97106 0
r.doughty@auckland.ac.nz
Contact person for public queries
Name 97107 0
Prof Rob Doughty
Address 97107 0
Heart Foundation Chair of Heart Health
University of Auckland
Dept of Medicine
Park Road
Grafton
Auckland 1024
Country 97107 0
New Zealand
Phone 97107 0
+64 9 9239804
Fax 97107 0
+64 9 377149
Email 97107 0
r.doughty@auckland.ac.nz
Contact person for scientific queries
Name 97108 0
Prof Rob Doughty
Address 97108 0
Heart Foundation Chair of Heart Health
University of Auckland
Dept of Medicine
Park Road
Grafton
Auckland 1024
Country 97108 0
New Zealand
Phone 97108 0
+64 9 9239804
Fax 97108 0
+64 9 377149
Email 97108 0
r.doughty@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Baseline characteristics and clinical outcomes
When will data be available (start and end dates)?
On trial completion (2023), and no end date as yet determined
Available to whom?
Researchers in the same field can request data by contact with the PI
Available for what types of analyses?
Available for appropriate meta-analyses addressing biomarker-guided risk management for patients with established CVD
How or where can data be obtained?
Through contact with the PI, with contact information available in the ANZCTR record.
What supporting documents are/will be available?
No other documents available
Summary results
No Results