Monotherapy versus dual therapy for the initial treatment of hypertension (PATHWAY-1): a randomised double-blind controlled trial

BMJ Open. 2015 Aug 7;5(8):e007645. doi: 10.1136/bmjopen-2015-007645.

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.

Trial registration number: UKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.

Keywords: CLINICAL PHARMACOLOGY.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure
  • Blood Pressure Monitoring, Ambulatory
  • Double-Blind Method
  • Drug Therapy, Combination
  • Essential Hypertension
  • Female
  • Hemodynamics
  • Humans
  • Hydrochlorothiazide / adverse effects
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Losartan / adverse effects
  • Losartan / therapeutic use
  • Male
  • Medication Adherence
  • Middle Aged
  • Prospective Studies
  • Young Adult

Substances

  • Antihypertensive Agents
  • Hydrochlorothiazide
  • Losartan

Associated data

  • EudraCT/2008-007749-29