Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial.
MacDonald, Thomas M
Cruickshank, J Kennedy
Webb, David J
Mackenzie, Isla S
Brown, Morris J
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MacDonald, T. M., Williams, B., Caulfield, M., Cruickshank, J. K., McInnes, G., Sever, P., Webb, D. J., et al. (2015). Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial.. BMJ Open, 5 (e007645) https://doi.org/10.1136/bmjopen-2015-007645
This is the final version of the article. It first appeared from BMJ via http://dx.doi.org/10.1136/bmjopen-2015-007645
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. TRIAL REGISTRATION NUMBER: UKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.
Funding statement The study is funded by a special project grant from the British Heart Foundation (number SP/08/002). Further funding is provided by Comprehensive Local Research Networks. The losartan and losartan-HCTZ were a generous gift from Dr Paul Robinson, Merck Sharpe Dohme, UK. Acknowledgements BW, PS, MC and MJB are NIHR Senior Investigators.
External DOI: https://doi.org/10.1136/bmjopen-2015-007645
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248696
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