The Precision HYpertenSIon Care (PHYSIC) study: a double-blind, randomized, repeated cross-over study

Abstract

High blood pressure is the leading risk factor for premature deaths and a major cost to societies worldwide. Effective blood pressure-lowering drugs are available, but patient adherence to them is low, likely partly due to side effects. To identify patient-specific differences in treatment effects, a repeated cross-over design, where the same treatment contrasts are repeated within each patient, is needed. Such designs have been surprisingly rarely used, given the current focus on precision medicine. The Precision HYpertenSIon Care (PHYSIC) study aims to investigate if there is a consistent between-person variation in blood pressure response to the common blood pressure-lowering drug classes of a clinically relevant magnitude, given the within-person variation in blood pressure. The study will also investigate the between-person variation in side effects of the drugs. In a double-blind, randomized, repeated cross-over trial, 300 patients with mild hypertension will be treated with four blood pressure-lowering drugs (candesartan, lisinopril, amlodipine, and hydrochlorothiazide) in monotherapy, with two of the drugs repeated for each patient. If the study indicates that there is a potential for precision hypertension care, the most promising predictors of blood pressure and side effect response to the drugs will be explored, as will the potential for development of a biomarker panel to rank the suitability of blood pressure-lowering drug classes for individual patients in terms of anticipated blood pressure effects and side effects, with the ultimate goal to maximize adherence. The study follows a protocol pre-registered at ClinicalTrials.gov with the identifier NCT02774460.