Optimal Treatment of Drug Resistant Hypertension

• Research type

  Research Study

• Full title

  Optimal Treatment of Drug Resistant Hypertension

• IRAS ID

  8290

• Contact name

  Morris Brown

• Sponsor organisation

  Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

• Eudract number

  2008-007149-30

• ISRCTN Number

  UKCRN4500

• Research summary

  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 NICE??s treatment recommendations in patients with resistant hypertension. These are patients whose blood pressure is >140 despite use of three drugs, and are consequently at high risk of stroke or heart attack. The study will be a randomised placebo-controlled double-blind crossover comparison of an alpha-blocker (a), ×ý-blocker (×ý), and K+sparing diuretic (??). These are the drug classes recommended as options by NICE. The trial is part of a programme of three trials funded by the British Heart Foundation and is designed to test two hypotheses: 1. That most resistant hypertension is due to salt retention and will respond best to Spironolactone; 2. That the best additional drug for individual patients can be predicted by measurement of the kidney hormone, renin, and choosing a, b or D respectively in patients with normal, high and low plasma renin levels.Patients will have a BP, at entry, above target on home monitoring despite supervised administration of maximum tolerated doses of the three first-line drug clases. Over 48 weeks they will then receive, in random order, either placebo or two doses each of doxazosin (a), bisoprolol (×ý) or spironolactone (??). Each treatment cycle will last 12 weeks, with a doubling of dose at 6 weeks. The primary outcome is difference between blood pressure on placebo and each patient??s best drug. 340 patients will provide 90% power, at a=0.01 to detect a 3 mmHg overall difference in home systolic BP 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 renin measurement in patients with resistant hypertension.

• REC name

  East of England - Cambridge South Research Ethics Committee

• REC reference

  08/H0305/75

• Date of REC Opinion

  14 Jan 2009

• REC opinion

  Further Information Favourable Opinion