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Trial registered on ANZCTR


Registration number
ACTRN12613000053729
Ethics application status
Approved
Date submitted
13/12/2012
Date registered
16/01/2013
Date last updated
15/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Targeted lowering of central blood pressure in patients with hypertension: a randomised controlled trial
Scientific title
Effect on left ventricular mass with targeted lowering of central blood pressure using spironolactone in patients with hypertension: a randomised controlled trial
Secondary ID [1] 281678 0
Nil
Universal Trial Number (UTN)
Trial acronym
The LOWCBP Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High blood pressure 287962 0
Condition category
Condition code
Cardiovascular 288349 288349 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral spironolactone, 25 mg/d, over 2 years
Intervention code [1] 286211 0
Treatment: Drugs
Comparator / control treatment
standard treatment of hypertension involving care supervised by the participants general practitioner
Control group
Active

Outcomes
Primary outcome [1] 288512 0
Left ventricular mass by magnetic resonance imaging
Timepoint [1] 288512 0
2 years
Secondary outcome [1] 300365 0
Clinic and home blood pressures (measured using automated devices) and 24 hour ambulatory blood pressure.
Timepoint [1] 300365 0
2 years
Secondary outcome [2] 300366 0
Aortic stiffness by tonometry and magnetic resonance imaging
Timepoint [2] 300366 0
2 years
Secondary outcome [3] 300367 0
Quality of life using SF-36 and Bulpitt health surveys
Timepoint [3] 300367 0
2 years

Eligibility
Key inclusion criteria
*Aged 18 – 70 years on stable antihypertensive therapy (at least one month).
*Taking at least one, but no more than three, antihypertensive drugs to lower BP (rationale for no more than 3 drugs is that this will rule out cases of complicated or resistant hypertension which may require special attention beyond this study protocol).
*Seated brachial BP <140/90 mmHg (controlled brachial BP).
*Seated central SBP greater than or equal to +0.5SD of age- and gender-specific normal values (uncontrolled central BP).
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Seated brachial BP greater than or equal to 140/90 mmHg (uncontrolled brachial BP)
*Seated brachial BP <140/90 mmHg but central SBP below +0.5SD of age- and gender-specific normal values
*Women who are pregnant, breastfeeding or of child bearing age with intending pregnancy.
*Concomitant therapy with both ACEi and ARB (due to risk of hyperkalaemia).
*Therapy with digoxin or lithium or nondepolarizing skeletal muscle relaxants (e.g. Tubocurarine).
*A clinical history of CVD which may affect estimation of central BP or complicate therapeutic decisions. This includes; established coronary artery disease, coronary artery bypass graft surgery, aortic valve stenosis (gradient >20 mmHg), systolic heart failure or ejection fraction <50% or other serious cardiovascular event within 6 months of enrolment.
*Chronic use of sex hormone therapy or non-steroidal anti-inflammatory drugs
*Using any aldosterone inhibitor (eplereone, spironolactone) within 30 days of enrolment.
*Contraindication to spironolactone including; anuria, acute renal insufficiency, significant impairment of renal excretory function (creatinine clearance less than or equal to 50 mL/min [Cockcroft-Gault formula]) or hyperkalemia (plasma potassium >5.0 mmol/l at initiation).
*Using potassium supplements or potassium-sparing diuretics (e.g. amiloride or triamterene).

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
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation with stratification based on 2D echo LV mass, age, sex and centre.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Prospective Randomised Open label Blinded Endpoint
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Between-group differences in endpoints over time will be assessed by multiple regression analysis controlling for cardiovascular risk factors

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)
ACT,QLD,TAS

Funding & Sponsors
Funding source category [1] 286467 0
Government body
Name [1] 286467 0
National Health and Medical Research Council of Australia
Address [1] 286467 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 286467 0
Australia
Primary sponsor type
Individual
Name
James Sharman
Address
Menzies Research Institute Tasmania
17 Liverpool Street,
Hobart, 7000 TAS
Country
Australia
Secondary sponsor category [1] 285255 0
None
Name [1] 285255 0
Address [1] 285255 0
Country [1] 285255 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288543 0
Human Research Ethics Committee (Tasmania)
Ethics committee address [1] 288543 0
Office of Research Services
University of Tasmania
Private Bag 1
Hobart TAS 7001
Ethics committee country [1] 288543 0
Australia
Date submitted for ethics approval [1] 288543 0
Approval date [1] 288543 0
01/06/2012
Ethics approval number [1] 288543 0
H0012445

Summary
Brief summary
High blood pressure (BP) is the most common modifiable cause of death from cardiovascular disease (CVD). Lowering BP with medication improves patient outcomes, but even in populations with normal upper arm (brachial) BP there remains considerable residual risk for CVD. Our recent pilot work found that much of this risk may be due to persistently elevated central BP. However, there has never been a trial to determine the clinical value of targeted central BP lowering. This remains the most significant question to be answered before central BP can be considered for routine clinical use, and is the aim of this project.

The proposed study will be a multi-centre, prospective, randomized, open-label, blinded endpoint (PROBE) trial over two years in 300 patients treated for hypertension who have controlled brachial BP but relatively high central BP. Randomisation to spironolactone (and lowering of central BP) is expected to significantly improve CVD risk, despite no significant change in clinic measured brachial BP.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36626 0
A/Prof James Sharman
Address 36626 0
Menzies Research Institute Tasmania
17 Liverpool Street, Hobart, TAS, 7000
Country 36626 0
Australia
Phone 36626 0
+61 3 6226 4709
Fax 36626 0
Email 36626 0
james.sharman@menzies.utas.edu.au
Contact person for public queries
Name 36627 0
A/Prof James Sharman
Address 36627 0
Menzies Research Institute Tasmania
17 Liverpool Street, Hobart, TAS, 7000
Country 36627 0
Australia
Phone 36627 0
+61 3 6226 4709
Fax 36627 0
Email 36627 0
james.sharman@menzies.utas.edu.au
Contact person for scientific queries
Name 36628 0
A/Prof James Sharman
Address 36628 0
Menzies Research Institute Tasmania
17 Liverpool Street, Hobart, TAS, 7000
Country 36628 0
Australia
Phone 36628 0
+61 3 6226 4709
Fax 36628 0
Email 36628 0
james.sharman@menzies.utas.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary