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

Abstract

BackgroundResistant 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/designThis 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.DiscussionIn 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 registrationSequential 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2343-3) contains supplementary material, which is available to authorized users.

Effect of Sequential Nephron Blockade versus Dual Renin-Angiotensin System Blockade Plus Bisoprolol in the Treatment of Resistant Hypertension, a Randomized Controlled Trial (Resistant Hypertension on Treatment - ResHypOT)

“…Detailed information about the study protocol was published previously. 19 Briefly, the ResHypOT (Resistant Hypertension on Treatment) trial of SNB versus DRASB plus bisoprolol in the treatment of resistant hypertension was an open-label, prospective, randomized, and parallel-group study with optional drug up-titration (ClinicalTrials.gov, identifier, NCT02832973, registered on 18 July 2016). Two therapeutic regimens for RHTN were compared, namely, SNB versus DRASB plus bisoprolol.…”

Qual O Papel Do Bloqueio Sequencial Do Néfron Na Hipertensão Resistente?

“…18 Os resultados desse estudo mostraram melhora significativa nos níveis pressóricos quando comparados com o grupo que recebeu associação de BRA e inibidores da enzima conversora da angiotensina (IECA), com efeitos adversos semelhantes nos dois grupos. 19 Recentemente, Fouassier e colaboradores demonstraram que pacientes com hipertensão resistente apresentam um risco maior para insuficiência cardíaca e após 12 semanas de tratamento com bloqueio sequencial do néfron obtiveram uma melhora rápida e significante dos marcadores ecocardiográficos de função diastólica. 20 (Figura 3) Figura 3.…”

Uncontrolled Arterial Hypertension: Kidney, Neurohormonal Imbalance, and Approaches to Antihypertensive Drug Therapy

“…Основной критерий оценки эффективности АГТ -величина снижения систолического, диастолического, среднего и пульсового АД спустя 20 нед лекарственной терапии. Дополнительные критерии оценки -функция почек и частота эпизодов гипотонии при сочетанном применении 5 препаратов с различными механизмами антигипертензивного действия [38].…”