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Trial registered on ANZCTR


Registration number
ACTRN12619000188134
Ethics application status
Approved
Date submitted
21/01/2019
Date registered
11/02/2019
Date last updated
11/02/2019
Date data sharing statement initially provided
11/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Atrial Fibrillation and Intensive Blood pressure lowering Pilot Study
Scientific title
Effect of Intensive Blood Pressure Control on the Burden of Atrial Fibrillation in Patients
with Non-permanent Atrial Fibrillation – Feasibility study
Secondary ID [1] 297108 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 311121 0
Hypertension 311122 0
Condition category
Condition code
Cardiovascular 309757 309757 0 0
Hypertension
Cardiovascular 310092 310092 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A combination of 4 ultra-low dose blood pressure lowering pills (irbesartan 37.5mg, amlodipine 1.25mg, indapamide 0.625mg, bisoprolol 2.5mg) packaged as Dose Administration Aids as initial or add-on treatment in addition to usual care management of blood pressure(BP) with standard BP target as recommended by guidelines. The 4 ultra-low dose blood pressure lowering pill will be taken once daily for 24 weeks. The other antihypertensive treatment is decided by the physicians. The medication adherence is measured by self-reported measures and drug tablet return.
Intervention code [1] 313376 0
Treatment: Drugs
Comparator / control treatment
Usual care with standard BP target as recommended by guidelines. Usual care means using the antihypertensive medications prescribed by physicians according to recommended by hypertension guidelines (Australian adult guideline for hypertension). Standard BP target is 140/90mmHg.
Control group
Active

Outcomes
Primary outcome [1] 318714 0
The primary outcome of this study will be difference between groups in AF burden–measured as percentage of time spent in AF in the period of 4 to 24 weeks as assessed by continuous monitoring. The monitoring will be conducted using intracardiac devices, e.g. loop recorder, pacemakers, etc.
Timepoint [1] 318714 0
4 to 24 weeks after initiation of study
Secondary outcome [1] 365790 0
Difference between groups in AF recurrence rate at 6 months. The AF recurrence will be assessed using intracardiac devices, e.g. loop recorder, pacemakers, etc.
Timepoint [1] 365790 0
6 months post randomization
Secondary outcome [2] 365791 0
Difference between groups in the time to first recurrence of AF. The AF recurrence will be assessed using intracardiac devices, e.g. loop recorder, pacemakers, etc.
Timepoint [2] 365791 0
Time of first AF recurrence during 6 months after randomization.
Secondary outcome [3] 365792 0
Difference between groups in total number of AF episodes during study period. The AF episodes will be assessed using intracardiac devices, e.g. loop recorder, pacemakers, etc.
Timepoint [3] 365792 0
6 months after randomization
Secondary outcome [4] 365793 0
Difference between groups in Quality life metrics using EQ-5D
Timepoint [4] 365793 0
6 month after randomization.
Secondary outcome [5] 365794 0
Difference between groups in blood pressure measures in unattended office SBP/ DBP at 24 weeks. Office blood pressure will be measured by electronic sphygmomanometer.
Timepoint [5] 365794 0
24 weeks after randomization.
Secondary outcome [6] 365795 0
Difference between groups in blood pressure measures in clinic SBP/DBP at 24 weeks. Office blood pressure will be measured by electronic sphygmomanometer.
Timepoint [6] 365795 0
24 weeks after randomization
Secondary outcome [7] 365796 0
Difference between groups in potentially related side-effects (dizziness, blurred vision, syncope/ collapse/ fall, chest pain/ angina, shortness of breath, cough, wheeze, ankle oedema, skin rash, itching, gout, hyperkalaemia, hypokalaemia, hyponatraemia, other) by medical records and reports from patients.
Timepoint [7] 365796 0
24 weeks after randomization.
Secondary outcome [8] 365798 0
Difference between groups in participant withdrawals from treatment by medical records.
Timepoint [8] 365798 0
24 weeks post randomization.
Secondary outcome [9] 365799 0
Percentage with any serious adverse events (SAEs) from medical records as well as patients' reports.
Timepoint [9] 365799 0
24 weeks after randomization.
Secondary outcome [10] 365800 0
Medication adherence evaluated by self-reported measures and pill counts. Self reported adherence is assessed from the answer of patients about the question 'what is the frequency of you to take antihypertensive medicine?'
Timepoint [10] 365800 0
24 weeks after randomization
Secondary outcome [11] 365801 0
Patient acceptability assessed at the end of study feedback questionnaire. The questionnaire is designed specifically for this study.
Timepoint [11] 365801 0
24 weeks after randomization

Eligibility
Key inclusion criteria
• Patients with non-permanent AF:
- Patients with paroxysmal AF (PAF) with AF burden greater than or equal to 1% or AF duration >10 minutes in the preceding 6 months identified either by:
A 5-7 day Holter monitor
An in-situ loop recorder (ILR)
An intracardiac device (pacemaker [PPM] or implanted cardiac defibrillator [ICD])
- Patients with an episode of persistent AF (PeAF) cardioverted to sinus rhythm in the last 12 months
• Adults greater than or equal to 18 years
• Continuous rhythm monitoring possible:
- pre-existing ILR, PPM or ICD, or
- Consent to having an ILR insertion
• A measure of Clinic SBP greater than or equal to 130 and/ or DBP greater than or equal to 80 mmHg documented on the electronic medical record in the last 6 months or by study staff
• With no intention to change antiarrhythmic therapy in the coming 1 year
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Hypertensive crisis by medical judgement
• Patients that are scheduled to have catheter ablation in the next 3 months
• Contraindication to irbesartan, amlodipine, indapamide or bisoprolol
• Women who are pregnant, breast feeding and/ or of childbearing potential and not using effective contraception throughout the study (pharmacological or barrier methods)
• Concomitant illness, physical impairment or mental condition which in the opinion of the study team/ primary care physician could interfere with the conduct of the study including outcome assessments
• Participation in a concurrent clinical trial of an investigational medical product which will interfere with blood pressure.
• Inability or unwillingness to provide written informed consent
• Medical illness with anticipated life expectancy < 3 months
• Responsible primary care or other responsible physician believes it is not appropriate to participate in the study or unable to complete the study procedures, e.g. secondary hypertension, resistant hypertension, some concomitant illness, physical impairment or mental condition which could interfere with the conduct of the study including outcome assessments.

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)
Yes. The allocation of each patient will be in a opaque envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of intervention and control will be in the ratio 1:1, variable block size and stratified by AF type. It will be conducted through a computer-based randomisation service.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All analyses of study outcomes will be conducted according to the principle of intention-to-treat. The primary analysis of change in AF burden during 24 weeks will be performed using an analysis of covariance (ANCOVA) including the treatment arm and baseline AF burden as covariates. Continuous secondary outcomes will be analysed similarly. For categorical secondary outcomes, chi square test will be used. Additional analyses will include 4-week and 24-week measurements in a longitudinal model including treatment arm, visit, and treatment by visit interaction as well as the baseline measurement. Within-patient correlations will be modelled using generalised estimating equations. A similar approach will be applied to binary endpoints with log-binomial regression used in place of linear regression. There will also be pre-defined subgroup analyses, including by baseline AF type, AF burden, gender, age and hypertension diagnosis. A detailed analysis plan will be developed prior to unblinding.

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)
NSW
Recruitment hospital [1] 12967 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 25445 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 301673 0
Charities/Societies/Foundations
Name [1] 301673 0
2018 Vanguard Grant of national heart foundation of Australia
Address [1] 301673 0
Level 2, 850 Collins street Docklands VIC 3008
Country [1] 301673 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Hawkesbury Rd, Westmead NSW 2145, Australia
Country
Australia
Secondary sponsor category [1] 301432 0
None
Name [1] 301432 0
Address [1] 301432 0
Country [1] 301432 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302392 0
Western Sydney Local Health District (WSLHD) Human Research Ethics Committee
Ethics committee address [1] 302392 0
Westmead Hospital, Hawkesbury & Darcy Roads, Westmead NSW 2145
Ethics committee country [1] 302392 0
Australia
Date submitted for ethics approval [1] 302392 0
13/06/2018
Approval date [1] 302392 0
03/12/2018
Ethics approval number [1] 302392 0
5764

Summary
Brief summary
The study hypothesizes it's feasible and effective to use intensive BP-lowering to reduce AF burden. In this pilot study of 60 patients with non-permanent AF who have a baseline BP >130/80, we aim to examine whether patients randomized to intensive BP-lowering in addition to usual care will have reduced AF burden as measured by continuous cardiac monitoring using an implanted device. Intensive BP-lowering will be achieved by randomizing patients to the quadpill (single pill with irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or to placebo on top of usual care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90078 0
Prof Clara Chow
Address 90078 0
Westmead Applied Research Centre (WARC)
Rm No 2041, Research & Education Network, Westmead Hospital, Westmead, NSW 2145
Country 90078 0
Australia
Phone 90078 0
+61 2 88903128
Fax 90078 0
Email 90078 0
clara.chow@sydney.edu.au
Contact person for public queries
Name 90079 0
Dr Marina Ali
Address 90079 0
Westmead Applied Research Centre (WARC)
Rm No 2041, Research & Education Network, Westmead Hospital, Westmead, NSW 2145
Country 90079 0
Australia
Phone 90079 0
+61 2 88903128
Fax 90079 0
Email 90079 0
marina.ali@sydney.edu.au
Contact person for scientific queries
Name 90080 0
Dr Marina Ali
Address 90080 0
Westmead Applied Research Centre (WARC)
Rm No 2041, Research & Education Network, Westmead Hospital, Westmead, NSW 2145
Country 90080 0
Australia
Phone 90080 0
+61 2 88903128
Fax 90080 0
Email 90080 0
marina.ali@sydney.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
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 1113 0
Ethical approval
Citation [1] 1113 0
Link [1] 1113 0
Email [1] 1113 0
Other [1] 1113 0
Summary results
No Results