Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial
Author(s)
Type
Journal Article
Abstract
Introduction: Previous studies have suggested that
more intensive initial therapy for hypertension results
in better long-term blood pressure (BP) control. We
test this hypothesis comparing initial monotherapy
with dual therapy in the management of essential
hypertension.
Methods and analysis: The study is a prospective,
multicentre, double-blind, active-controlled trial in
patients with essential hypertension. Around 50% of
patients studied will be newly diagnosed and the
others will be known hypertensives who previously
received only monotherapy. The trial is divided into
three phases as follows: Phase 1 (Week 0–Week 16):
Randomised, parallel-group, masked assignation to
either combination or monotherapy. Phase 2 (Week
17–Week 32): Open-label combination therapy. Phase
3 (Week 33–Week 52): Open-label combination therapy
plus open-label add-on (if BP is above 140/
90 mm Hg). Hierarchical primary end points are:
a comparison of home BP (home systolic blood
pressure (HSBP)) averaged over the duration of phase
1 and 2 in the combination versus monotherapy arms.
If combination is superior in this analysis, then the
averaged mean HSBP between initial monotherapy and
initial combination therapy at the end of phase 2 will
be compared. Secondary end points include: BP
control at 1 year; the role of age, baseline renin,
sodium status, plasma volume, haemodynamic
compensation and peripheral resistance on BP control;
validation of the National Institute for Clinical
Excellence/British Hypertension Society joint guideline
algorithm; safety and tolerability of combination
therapy; and the impact of combination versus
monotherapy on left ventricular mass and aortic pulse
wave velocity. A sample size of 536 (268 in each
group) will have 90% power to detect a difference in
means of 4 mm Hg.
Ethics and dissemination: PATHWAY 1 was
approved by UK ethics (REC Reference 09/H0308/132).
Trial results will be published and all participating
subjects will be informed of the results
more intensive initial therapy for hypertension results
in better long-term blood pressure (BP) control. We
test this hypothesis comparing initial monotherapy
with dual therapy in the management of essential
hypertension.
Methods and analysis: The study is a prospective,
multicentre, double-blind, active-controlled trial in
patients with essential hypertension. Around 50% of
patients studied will be newly diagnosed and the
others will be known hypertensives who previously
received only monotherapy. The trial is divided into
three phases as follows: Phase 1 (Week 0–Week 16):
Randomised, parallel-group, masked assignation to
either combination or monotherapy. Phase 2 (Week
17–Week 32): Open-label combination therapy. Phase
3 (Week 33–Week 52): Open-label combination therapy
plus open-label add-on (if BP is above 140/
90 mm Hg). Hierarchical primary end points are:
a comparison of home BP (home systolic blood
pressure (HSBP)) averaged over the duration of phase
1 and 2 in the combination versus monotherapy arms.
If combination is superior in this analysis, then the
averaged mean HSBP between initial monotherapy and
initial combination therapy at the end of phase 2 will
be compared. Secondary end points include: BP
control at 1 year; the role of age, baseline renin,
sodium status, plasma volume, haemodynamic
compensation and peripheral resistance on BP control;
validation of the National Institute for Clinical
Excellence/British Hypertension Society joint guideline
algorithm; safety and tolerability of combination
therapy; and the impact of combination versus
monotherapy on left ventricular mass and aortic pulse
wave velocity. A sample size of 536 (268 in each
group) will have 90% power to detect a difference in
means of 4 mm Hg.
Ethics and dissemination: PATHWAY 1 was
approved by UK ethics (REC Reference 09/H0308/132).
Trial results will be published and all participating
subjects will be informed of the results
Date Issued
2015-08-07
Date Acceptance
2015-06-15
Citation
BMJ Open, 2015, 5 (8)
ISSN
2044-6055
Publisher
BMJ Publishing Group
Journal / Book Title
BMJ Open
Volume
5
Issue
8
Copyright Statement
This is an Open Access article distributed in accordance with
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work noncommercially,
and license their derivative works on different terms, provided
the original work is properly cited and the use is non-commercial. See: http://
creativecommons.org/licenses/by-nc/4.0/
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work noncommercially,
and license their derivative works on different terms, provided
the original work is properly cited and the use is non-commercial. See: http://
creativecommons.org/licenses/by-nc/4.0/
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
RESISTANT HYPERTENSION
MANAGEMENT
AMLODIPINE
OUTCOMES
Publication Status
Published
Article Number
e007645