Monotherapy Versus Dual Therapy for Initial Treatment for Hypertension
- Conditions
- Hypertension, Resistant to Conventional TherapyEssential Hypertension
- Interventions
- Registration Number
- NCT00994617
- Lead Sponsor
- University of Cambridge
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 600
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination Therapy Losartan and hydrochlorothiazide Patients treated with combination therapy of Hydrochlorthiazide plus Losartan. Losartan will be force-titrated from 50 to 100mg, Hydrochlorothiazide will be force-titrated from 12.5mg to 25mg Monotherapy Hydrochlorothiazide switched over with Losartan at 8 weeks Initial monotherapy Hydrochlorothiazide 12.5mg -25mg Crossed over with Losartan 50 -100mg at 8 weeks
- Primary Outcome Measures
Name Time Method Change in mean home systolic BP for the group treated initially with monotherapy compared to the group treated initially with combination therapy. 1 year
- Secondary Outcome Measures
Name Time Method A comparison the proportion of patients who drop out of the trial at any stage after randomisation or who require further antihypertensive treatment 1 year
Trial Locations
- Locations (13)
Professor Morris Brown
🇬🇧Cambridge, Cambridgeshire, United Kingdom
NHS Lothian/University of Edinburgh
🇬🇧Edinburgh, United Kingdom
NHS Ayrshire
🇬🇧Ayrshire, United Kingdom
NHS Tayside/University of Dundee
🇬🇧Dundee, United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Ixworth GP Practice
🇬🇧Ixworth, United Kingdom
Norfolk and Norwich University Hospital NHS Trust
🇬🇧Norwich, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
NHS Greater Glasgow and Clyde/University of Glasgow
🇬🇧Glasgow, United Kingdom
Barts and the London School of Medicine and Dentistry
🇬🇧London, United Kingdom
Guys and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom