Monotherapy Versus Dual Therapy for Initial Treatment for Hypertension
Pathway 1
1 other identifier
interventional
600
1 country
13
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jan 2010
Longer than P75 for phase_4
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2009
CompletedFirst Posted
Study publicly available on registry
October 14, 2009
CompletedStudy Start
First participant enrolled
January 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2014
CompletedJune 12, 2013
June 1, 2013
4.9 years
October 13, 2009
June 11, 2013
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
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
Study Arms (2)
Combination Therapy
EXPERIMENTALPatients 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
ACTIVE COMPARATORInitial monotherapy Hydrochlorothiazide 12.5mg -25mg Crossed over with Losartan 50 -100mg at 8 weeks
Interventions
Losartan 50 -100mg Hydrochlorothiazide 12.5mg -25mg
Hydrochlorothiazide 12.5-25mg crossed over with Losartan 50-100mg
Eligibility Criteria
You may qualify if:
- Aged 18-79
- Male subjects or female subjects taking adequate contraception such as the oral contraceptive pill, an intra uterine device or who are surgically sterilised or postmenopausal Females
- Either never-treated or received a maximum of one antihypertensive drug class in the previous year
- Patients will be excluded for ANY ONE of the following reasons
- Clinic SBP \> 200 mmHg or DBP \> 120 mmHg, with PI discretion to override if home BP measurements are lower
- Secondary or accelerated phase hypertension
- eGFR \< 45 mls/min
- Contra-indication or previous intolerance to any trial therapy
- Failure to record required home BP readings during placebo run-in.
- Significant co-morbidity (investigator opinion but to include alcoholism, terminal illness, documented non-attendance at clinics etc)
- Diabetes type 1
- Plasma K+ outside normal range on two successive measurements during screening
- Requirement for treatment with ≥2 drugs (which can be a CCB and/or {ACEi OR ARB OR direct renin inhibitor OR β-blocker}) in order to reduce blood pressure to ≤180/120 mmHg
- Requirement for diuretic therapy (other than for hypertension)
- Requirement for ACE inhibitor (or ARB) therapy (other than for hypertension)
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Cambridgelead
- British Heart Foundationcollaborator
Study Sites (13)
Professor Morris Brown
Cambridge, Cambridgeshire, CB22QQ, United Kingdom
NHS Ayrshire
Ayrshire, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
NHS Tayside/University of Dundee
Dundee, United Kingdom
NHS Lothian/University of Edinburgh
Edinburgh, United Kingdom
NHS Greater Glasgow and Clyde/University of Glasgow
Glasgow, United Kingdom
Ixworth GP Practice
Ixworth, United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, 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
Central Manchester University Hospitals NHS Foundation Trust
Manchester, United Kingdom
Norfolk and Norwich University Hospital NHS Trust
Norwich, United Kingdom
Related Publications (1)
MacDonald TM, Williams B, Webb DJ, Morant S, Caulfield M, Cruickshank JK, Ford I, Sever P, Mackenzie IS, Padmanabhan S, McCann GP, Salsbury J, McInnes G, Brown MJ; British Hypertension Society Programme of Prevention And Treatment of Hypertension With Algorithm-based Therapy (PATHWAY). Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial. J Am Heart Assoc. 2017 Nov 18;6(11):e006986. doi: 10.1161/JAHA.117.006986.
PMID: 29151036DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Professor MJ Brown, FMedSci
University of Cambridge
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof Morris Brown
Study Record Dates
First Submitted
October 13, 2009
First Posted
October 14, 2009
Study Start
January 1, 2010
Primary Completion
December 1, 2014
Study Completion
December 1, 2014
Last Updated
June 12, 2013
Record last verified: 2013-06