title: Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial.
abstract: BACKGROUND
  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
  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.
  
  
  BACKGROUND
  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.
  
  
  BACKGROUND
  UKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.
authors.affiliation: Medicines Monitoring Unit, Medical Research Institute, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: MacDonald
authors.affiliation: Institute of Cardiovascular Sciences and National Institute for Health Research (NIHR) UCL/UCL Hospitals Biomedical Research Centre, University College London, London, UK.
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: William Harvey Institute, Queen Mary's School of Medicine, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Caulfield
authors.affiliation: Department of Cardiovascular Medicine & Diabetes, King's College London, London, UK.
authors.forename: J Kennedy
authors.initials: JK
authors.lastname: Cruickshank
authors.affiliation: Institute of Cardiovascular Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: McInnes
authors.affiliation: International Centre for Circulatory Health, Imperial College, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Sever
authors.affiliation: Clinical Pharmacology Unit, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
authors.affiliation: Medicines Monitoring Unit, Medical Research Institute, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
authors.forename: Isla S
authors.initials: IS
authors.lastname: Mackenzie
authors.affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Salsbury
authors.affiliation: Medicines Monitoring Unit, Medical Research Institute, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Morant
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000075222:Essential Hypertension; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D019808:Losartan
keywords: CLINICAL PHARMACOLOGY