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Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension – study protocol for a randomized controlled trial

Authors: Elizabeth do Espirito Santo Cestário, Letícia Aparecida Barufi Fernandes, Luiz Tadeu Giollo-Júnior, Jéssica Rodrigues Roma Uyemura, Camila Suemi Sato Matarucco, Manoel Idelfonso Paz Landim, Luciana Neves Cosenso-Martin, Lúcia Helena Bonalume Tácito, Heitor Moreno Jr., José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo

Published in: Trials | Issue 1/2018

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Abstract

Background

Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney.

Methods/design

This is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride.
On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group.

Discussion

In recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney.

Trial registration

Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973. Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.
Appendix
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Metadata
Title
Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension – study protocol for a randomized controlled trial
Authors
Elizabeth do Espirito Santo Cestário
Letícia Aparecida Barufi Fernandes
Luiz Tadeu Giollo-Júnior
Jéssica Rodrigues Roma Uyemura
Camila Suemi Sato Matarucco
Manoel Idelfonso Paz Landim
Luciana Neves Cosenso-Martin
Lúcia Helena Bonalume Tácito
Heitor Moreno Jr.
José Fernando Vilela-Martin
Juan Carlos Yugar-Toledo
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-2343-3

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