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Trial registered on ANZCTR


Registration number
ACTRN12618000074291
Ethics application status
Approved
Date submitted
29/11/2017
Date registered
18/01/2018
Date last updated
18/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of central high blood pressure treatment on atrial fibrillation outcomes.
Scientific title
“The IMPACT of treating central HIGH blood pressure on Atrial Fibrillation (AF) and cardiovascular outcomes in known AF patients. (HIGH IMPACT- AF STUDY)”
Secondary ID [1] 292393 0
None
Universal Trial Number (UTN)
U1111-1199-0564
Trial acronym
HIGH IMPACT AF study
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 303958 0
Hypertension (HTN) 303959 0
Condition category
Condition code
Cardiovascular 303313 303313 0 0
Other cardiovascular diseases
Cardiovascular 303314 303314 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The interventional arm will get treated as per their non-invasive central (aortic) blood pressure targets as per established reference values (European Heart Journal, Volume 35, Issue 44, 21 November 2014, Pages 3122–3133, https://doi.org/10.1093/eurheartj/ehu293) with the appropriate anti-HTN (ACE-I/ARBs, Ca Channel blockers and diuretics as first line therapy as per AHA 2017 guidelines ). The therapy will be titrated as per blood pressure response during three monthly follow ups for next 2 years post recruitment. The impact of central blood pressure treatment on AF and cardiovascular outcomes will be studied.
During the three monthly follow ups side effects of the medications including postural hypotension and affect on renal function will be recorded. The anti-HTN treatment will be gradually titrated as per symptoms and target BP goals.
The treatment target for non-invasive central systolic pressure will be as follows:
(Int. J Angiol.2010 Winter; 19(4):e132-e134)
Age (yrs.) Range (mmHg) Average (mmHg)
20-30 90-112 101
30-40 94-116 105
40-50 97-119 108
50-60 101-123 112
60-70 104-126 115
70-80 108-130 119
80-90 111-133 122

The impact of central blood pressure control will be compared with control group re AF and CV outcomes.
Intervention code [1] 298566 0
Treatment: Drugs
Intervention code [2] 298567 0
Lifestyle
Comparator / control treatment
The control patients will have their brachial blood pressure treated as per current AHA and ESC guidelines (130/80mmHg for low cardiovascular (CV) risk (<1%/year) and 120/75 mmHg for high CV risk individuals(>1%/year), with the appropriate anti-HTN treatment (ACE-I/ARB, Ca channel blockers and diuretics as first line). The treatment will be titrates as per BP response and symptoms of postural hypotension along with renal function will be monitored during 6 monthly follow up for next 2 years.
Control group
Active

Outcomes
Primary outcome [1] 302698 0
AF recurrence on 4-7 days Holter monitoring
Timepoint [1] 302698 0
6 monthly follow up for next 18 months to look at AF recurrence (Time point for Primary endpoint 18 months)
Primary outcome [2] 302699 0
Hospital admission due to AF
Timepoint [2] 302699 0
6 monthly follow up for next 18 months to look at the admissions due to AF (time point for the primary endpoint will be 18 months)
Secondary outcome [1] 336774 0
Composite endpoint: Appraise the progression of HTN induced end organ insult by targeting central or peripheral blood pressure including LVH assessed by echocardiography as per ESC guidelines, HTN induced retinopathy characterized with annual retinal screening or nephropathy estimated by monitoring albumin creatinine ration in urine as well as serum creatinine.
Timepoint [1] 336774 0
For intervention arm: (24 months follow up)
3monthly follow up to check for side effects of anti-HTN therapy including postural hypotension and acute kidney injury (AKI).
12 monthly follow up for retinopathy, LVH and nephropathy

For control arm (24 months follow up)
6 monthly follow up for medication side effects including postural hypotension and AKI.
12 monthy follow up for LVH, retinopathy and nephropathy.

Eligibility
Key inclusion criteria
Patient with known AF
Age (18-80yrs.)
Non- Pregnant
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age <18years
2. Contraindications to exercise stress test (EST)
3. Pregnancy
4. Active malignancy or severe illness
5. Active Inflammatory disorder
6. Severe Aortopathy
7. Advanced valvular heart disease including aortic insufficiency (AI)
8. Constrictive or restrictive cardiomyopathy
9. Contraindications to non-contrast CMR (in selected patients scheduled for PVI)

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)
Central randomisation by computer software programme (RED CAPS)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerized sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculation
AF recurrence rate can well be upto 40-50% in 2 years. To study the impact of treatment of central or peripheral blood pressure to predefined targets, on AF outcome, 90 patients are required in each arm to detect a 20% difference in AF outcomes. With a dropout rate of 20% in mind, we will aim for recruiting 120 patients in each arm.
Statistical Analysis:
Continuous variables will be reported as mean with standard deviation (SD). Results will be expressed as mean +/- SEM with p value of <0.05 considered statistically significant. Correlation, intra-class correlation analysis, Student’s t-test and Bland– Altman plots will be used to assess the agreement between the peripheral and central blood pressure recordings.
Other ad hoc summary or analysis may be performed as necessary. The results of this study would be expected to be published in an internationally recognised Cardiology journal.

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)
SA
Recruitment hospital [1] 8507 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 16600 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 296948 0
Hospital
Name [1] 296948 0
Royal Adelaide Hospital
Address [1] 296948 0
North Terrace, Adelaide SA 5000
Country [1] 296948 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 295953 0
None
Name [1] 295953 0
Address [1] 295953 0
Country [1] 295953 0
Other collaborator category [1] 279637 0
Individual
Name [1] 279637 0
Prof Prash Sanders
Address [1] 279637 0
Cardiovascular Centre, 62 Beulah Road Norwood, Adelaide SA 5067
Country [1] 279637 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298153 0
CALHN, Royal Adelaide Hospital, UOA, Adelaide
Ethics committee address [1] 298153 0
Human Ethics and Research Committtee
Royal Adelaide Hospital, UOA
North Terrace Adelaide, SA 5000
Ethics committee country [1] 298153 0
Australia
Date submitted for ethics approval [1] 298153 0
04/10/2017
Approval date [1] 298153 0
22/11/2017
Ethics approval number [1] 298153 0

Summary
Brief summary
Amongst the attributable factors, hypertension is the predominant risk leading to atrial fibrillation (AF) and premature cardiovascular events. As compare to brachial blood pressure, central blood pressure and aortic stiffness assessment even in “normotensives”, has shown improve predictability of cardiovascular outcomes including atrial fibrillation. Cardiovascular risk stratification based on central blood pressure indices can be more relevant as it demonstrates the central pulsatile load an organ is exposed to and reveals early vascular remodelling of central arterial tree resulting in aortic stiffness. Non-invasively derived central hemodynamic indices have been demonstrated to predict cardiovascular outcomes in a variety of settings.
We propose a single blinded, randomised prospective trial to risk profile our AF patients according to their non-invasive assessment of peripheral or central blood pressure including aortic stiffness estimate. The impact of central or peripheral blood pressure treatment , on AF outcomes will be analysed. In addition, the relationship between central or peripheral high blood pressure and non-invasive indicators of end organ (cardiac, vascular, renal and retinal) injury will be explored.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA
Attachments [2] 2232 2232 0 0

Contacts
Principal investigator
Name 76158 0
Prof Prash Sanders
Address 76158 0
Centre for Heart Rhythm Disorders,
Royal Adelaide Hospital, UOA
North Terrace, Adelaide SA 5000
Country 76158 0
Australia
Phone 76158 0
+61882222327
Fax 76158 0
Email 76158 0
prash.sanders@adelaide.edu.au
Contact person for public queries
Name 76159 0
Prof Prash Sanders
Address 76159 0
Centre for Heart Rhythm Disorders,
Royal Adelaide Hospital, UOA
North Terrace, Adelaide SA 5000
Country 76159 0
Australia
Phone 76159 0
+61882222327
Fax 76159 0
Email 76159 0
prash.sanders@adelaide.edu.au
Contact person for scientific queries
Name 76160 0
Prof Prash Sanders
Address 76160 0
Centre for Heart Rhythm Disorders,
Royal Adelaide Hospital, UOA
North Terrace, Adelaide SA 5000
Country 76160 0
Australia
Phone 76160 0
+61882222327
Fax 76160 0
Email 76160 0
prash.sanders@adelaide.edu.au

No information has been provided regarding IPD availability
How or where can supporting documents be obtained?
Type [1] 853 0
Ethical approval
Citation [1] 853 0
Link [1] 853 0
Email [1] 853 0
Other [1] 853 0
Type [2] 854 0
Study protocol
Citation [2] 854 0
Link [2] 854 0
Email [2] 854 0
Other [2] 854 0
Type [3] 855 0
Informed consent form
Citation [3] 855 0
Link [3] 855 0
Email [3] 855 0
Other [3] 855 0
Type [4] 856 0
Informed consent form
Citation [4] 856 0
Link [4] 856 0
Email [4] 856 0
Other [4] 856 0
Summary results
No Results