Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001445167
Ethics application status
Approved
Date submitted
10/10/2019
Date registered
18/10/2019
Date last updated
22/11/2024
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
Primary outcome [2] 339969 0
Hierarchical composite, stratified by baseline risk: 1. Death from any cause 2. Hospitalisation for recurrent ACS or heart failure 3. Hospitalisation for other IHD (including coronary revascularisation [CABG or PCI] during unplanned hospital admission) 4. Hospitalisation for cerebrovascular disease (including stroke and TIA) 5. Change in systolic blood pressure from baseline to 3 months Clinical events will be collected by anonymised linkage to the NZ national datasets (mortality and hospitalisations). All events in the hierarchical end-point will be collected with higher priority given to the most severe event (as per the order of the events listed).
Timepoint [2] 339969 0
Median follow up 2 years 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
Secondary outcome [2] 442112 0
Death from any cause (national administrative dataset linkage)
Timepoint [2] 442112 0
Median follow up of 2 years post-randomisation
Secondary outcome [3] 442113 0
Hospitalisation for recurrent ACS or heart failure (national administrative dataset linkages)
Timepoint [3] 442113 0
Median follow up of 2 years post-randomisation
Secondary outcome [4] 442114 0
Hospitalisation for recurrent ACS or heart failure (national administrative dataset linkages)
Timepoint [4] 442114 0
Median follow up 2 years post-randomisation
Secondary outcome [5] 442115 0
Hospitalisation for other IHD event (defined as any IHD ICD coded event excluding ACS: data from national administrative dataset linkages)
Timepoint [5] 442115 0
Median follow up 2 years post-randomisation
Secondary outcome [6] 442116 0
Hospitalisation for other IHD event (defined as any IHD ICD coded event excluding ACS: data from national administrative dataset linkages)
Timepoint [6] 442116 0
The trial commenced in December 2019, was delayed during the pandemic, end-point revised as per the previous section (primary end-point) Enrolment still ongoing when this revision was made Median follow up 2 years post-randomisation
Secondary outcome [7] 442117 0
Hospitalisation for cerebrovascular disease (data available from national administrative dataset linkages)
Timepoint [7] 442117 0
The trial commenced in December 2019, was delayed during the pandemic, end-point revised as per the previous section (primary end-point) Enrolment still ongoing when this revision was made Median follow up 2 years post-randomisation
Secondary outcome [8] 442119 0
Change in systolic blood pressure from baseline to 3 months (BP recorded by sphygmomanometer at clinic visit)
Timepoint [8] 442119 0
The trial commenced in December 2019, was delayed during the pandemic, end-point revised as per the previous section (primary end-point) Enrolment still ongoing when this revision was made Median follow up 2 years post-randomisation
Secondary outcome [9] 442120 0
Change in systolic blood pressure from baseline to 3 months (BP recorded by sphygmomanometer at clinic visit)
Timepoint [9] 442120 0
Baseline to 3 month follow up post-randomisation

Eligibility
Key inclusion criteria
Primary diagnosis of acute coronary syndrome
Age > 18yrs
Minimum age
18 Years
Maximum age
No limit
Sex
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 will be analysed using the win ratio approach using patient pairs within the same strata of risk which reduces variability and thus enhances statistical power.
BioMACS has a 1:1 randomisation, we assume a 20% reduction in risk with the Intervention, and if only 10% of the cohort end up with a tie at the end of the hierarchy of outcome comparisons, we need 1028 people in the trial for 80% power.
Statistical analyses will be undertaken by study statistician using the software "R".
A formal statistical analysis plan will be developed to prospectively detail the approach to analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/12/2019
Actual
2/12/2019
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1028
Accrual to date
948
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
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
Approved
Ethics committee name [1] 304484 0
Health and Disability Ethics Committee
Ethics committee address [1] 304484 0
Ethics committee country [1] 304484 0
New Zealand
Date submitted for ethics approval [1] 304484 0
28/08/2019
Approval date [1] 304484 0
25/11/2019
Ethics approval number [1] 304484 0

Summary
Brief summary
Trial website
Trial related presentations / publications
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
[email protected]
Contact person for public queries
Name 97107 0
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
[email protected]
Contact person for scientific queries
Name 97108 0
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
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers in the same field can request data by contact with the PI

Conditions for requesting access:
• -

What individual participant data might be shared?
• Baseline characteristics and clinical outcomes

What types of analyses could be done with individual participant data?
• Available for appropriate meta-analyses addressing biomarker-guided risk management for patients with established CVD

When can requests for individual participant data be made (start and end dates)?
From:
On trial completion (2025), and no end date as yet determined

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Through contact with the PI, with contact information available in the ANZCTR record.

Are there extra considerations when requesting access to individual participant data?
No


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.