This study was recommended by NICE, as part of its 2006 guidance for the treatment of
hypertension, and is urgently required to provide evidence for the treatment recommendations
in patients with resistant hypertension. The study will be a randomised placebo-controlled
double-blind crossover comparison of an α-blocker (α), β-blocker (β), and K+-sparing diuretic
(∆).
Patients will have a BP at entry above target on ABPM or home monitoring despite supervised
administration of maximum tolerated doses of A+C+D. Over 48 weeks they will then receive, in
random order either placebo or two doses each of doxazosin (α), bisoprolol (β) or
spironolactone (∆). Each treatment cycle will last 12 weeks, with a forced dose-doubling at 6
weeks.
The time course for the study will be similar to study one. 340 patients will provide 90%
power, at α=0.01 to detect a 3 mmHg overall difference in home sBP between any one drug and
placebo, with spironolactone hypothesized to be best overall. The study will be able to
detect a 6 mmHg difference in sBP between each subject's best and second-best drug predicted
by tertile of plasma renin, justifying routine use of the measurement in patients with
resistant hypertension.