To test whether the current custom of initiating treatment for hypertension with a single drug is less effective in the short-term than initial combination therapy, and results in the eventual need for comparatively more antihypertensive drug therapy.
To determine if patients randomised to more aggressive (combination therapy) treatment for the initial treatment of hypertension have better blood pressure control compared to those randomised to less aggressive (monotherapy) treatment despite subsequent add-on treatment being similar in each group. This will test the hypothesis that monotherapy patients 'never catch up' with combination therapy patients. 1. To determine if this 'never catch-up' phenomenon of improved BP control persists for at least one year. 2. To understand the underlying mechanism of improved BP control; specifically: 1. To determine if it is due to haemodynamic compensation, such as increased sodium retention and volume expansion. 2. To determine if it is due to increased peripheral resistance. 3. To understand the predictors of BP control i.e. age, baseline renin status, sodium status and plasma volume. 4. To validate the National Institute for Clinical Excellence / British Hypertension Society joint guideline ACD algorithm by comparing BP control in the monotherapy crossover arm of phase 1 and to correlate this with age (≤ 55 or \> 55y), and baseline characteristics such as renin. 5. To determine the safety and tolerability of a strategy of prescribing combination therapy as the initial step versus monotherapy as the initial step.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
600
Losartan 50 -100mg Hydrochlorothiazide 12.5mg -25mg
Hydrochlorothiazide 12.5-25mg crossed over with Losartan 50-100mg
Professor Morris Brown
Cambridge, Cambridgeshire, United Kingdom
RECRUITINGNHS Ayrshire
Ayrshire, United Kingdom
Change in mean home systolic BP for the group treated initially with monotherapy compared to the group treated initially with combination therapy.
Time frame: 1 year
A comparison the proportion of patients who drop out of the trial at any stage after randomisation or who require further antihypertensive treatment
Time frame: 1 year
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University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
RECRUITINGNHS Tayside/University of Dundee
Dundee, United Kingdom
RECRUITINGNHS Lothian/University of Edinburgh
Edinburgh, United Kingdom
RECRUITINGNHS Greater Glasgow and Clyde/University of Glasgow
Glasgow, United Kingdom
RECRUITINGIxworth GP Practice
Ixworth, United Kingdom
RECRUITINGUniversity Hospitals of Leicester NHS Trust
Leicester, United Kingdom
RECRUITINGBarts and the London School of Medicine and Dentistry
London, United Kingdom
RECRUITINGGuys and St Thomas' NHS Foundation Trust
London, United Kingdom
RECRUITING...and 3 more locations