Trial of preventing hypertension: Design and 2-year progress report

The TRial Of Preventing HYpertension (TROPHY) study is an investigator-initiated trial to examine whether early pharmacological treatment in subjects with "high-normal" blood pressure (BP) might prevent or delay the development of clinical hypertension. This is a 4-year, multicenter, randomized, double-blind study in untreated subjects aged 30 to 65 years with entry BPs of 130 to 139/≤89 or ≤139/85 to 89. The participants were randomized either to placebo or to a fixed (16 mg once daily) dose of candesartan cilexetil (candesartan). After 2 years, the candesartan group was switched to placebo, and the placebo group continued taking placebo. The main outcome measure was the development of clinical (treatment-requiring) hypertension assessed by an automated (blinded) BP measurement device. We randomized 809 subjects (59% males, average age 49.0 ± SD 8.1 years) in 71 study centers in the United States. The entry BP was 134 ± 4.3/84.8 ± 3.9 mm Hg. During the first 2 years, 187 subjects (23%) developed clinical hypertension. All have been given antihypertensive treatment, and 170 continue to be followed in study centers. The study dropout rate is 14.8% (120 subjects). The hypertension rates are higher than anticipated, whereas the rates of dropout are within the sample size projections; thus, the study will have sufficient power to evaluate its hypotheses. In this article, we describe baseline characteristics of TROPHY subjects and discuss novel analytical issues and statistical approaches to evaluate the findings in this trial of primary prevention of hypertension.