PROTOCOL OF THE HYPERTENSION THERAPY WITH IRBESARTAN VERSUS EPLERENONE FOR OBESE HYPERTENSIVE PATIENTS (HEBRO)

Abstract

Objective: Hypertension and obesity often coexist and activation of the renin-angiotensin- aldosterone (RAS) axis plays a major pathophysiological role. Since obese hypertensive patients are less frequently controlled within-goal compared with hypertensives without obesity, we aimed to determine whether RAS blocking at the level of aldosterone (eplerenone) is accompanied by better blood pressure (BP) efficacy compared with the traditional blocking at an intermediate axis level (irbesartan). Design and method: A multicentre Hellenic-ESH Excellence centres setting was chosen and a parallel open-label, randomized-controlled, phase IV trial was projected to demonstrate two-sided superiority between comparator-drugs over a period 24-weeks. We include obese (body mass index from 30 to less than 40, aged 30–75 years), newly diagnosed or drug-naive patients with mild to moderate hypertension, confirmed by ambulatory BP monitoring (ABPM). Randomization (1:1) to either eplerenone or irbesartan will be pursued taking into account age, gender, baseline office systolic BP levels and renal function. At eight, sixteen and twenty-four weeks, ABPM will demonstrate BP control, and a stepped-care approach with the addition of amlodipine and indapamide will be followed in those uncontrolled during the two intermediate trial time frames. Renal function, electrolyte disorders, fatal and non-fatal cardiovascular events and adverse events will be also evaluated. A sample size of 336 patients (allowing 15% dropouts) will confer 80% power to detect a 4 mmHg ABPM averaged systolic BP difference. The primary endpoint is the 24-h systolic BP difference at 24 weeks. Secondary endpoints: 1) the change in office BP at 24 weeks;2) the intermediate change in 24-h systolic BP;3) the change in left ventricular mass and microalbuminuria at 24 weeks; 4) discontinuations from treatment because of adverse events. Trial registration: Clinicaltrials.gov NCT03476616;EudraCT: 2018-004809-58. Results: Ethics approval has been obtained from the hospital ethic committee board and the Hellenic National Organization for Medicines. The study will initiate in May 2019. Conclusions: Preliminary data are expected in 2020–2021 and the final results are anticipated in 2022. Randomized evidence to support further large-scale trials will be provided to refine research in this field. Findings will be published in peer-reviewed medical journals.