Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension
Status:
Completed
Trial end date:
2018-03-01
Target enrollment:
Participant gender:
Summary
A randomized clinical trial comparing sequential nephron blockage (SNB) with dual blockade of
the renin-angiotensin system (RAAS) plus bisoprolol (DBB) in the treatment of resistant
arterial hypertension (RH) was designed to investigate the importance of the SNB and the
contribution of its volume component versus DBB and the importance of the serum renin in
maintaining BP levels. This randomized trial with two treatment arms could help tailor
therapy by identifying a more effective choice to control hypertension whether by acting on
the control of volume or sodium balance, or by acting on the effects of the RAAS on the
kidney.
Methods - Participants: 80 patients undergoing treatment for RH with losartan (100-200 mg),
chlorthalidone (25 mg), and amlodipine (5 mg) will be randomly divided into two groups after
applying inclusion and exclusion criteria.
Group 1: Sequential nephron blockade (SNB Group) n = 40 Group 2: Dual blockade of the RAAS
plus bisoprolol (DBB Group) n = 40 Intervention: SNB consists in a progressive increase in
sodium depletion. After the administration of a thiazide diuretic (chlorthalidone) and
aldosterone receptor blocker, low doses of furosemide are administered and subsequently
amiloride is prescribed to enhance the natriuretic effect.
The dual blockade of the RAAS plus bisoprolol is used to increase the effect of angiotensin
receptor 1 blockers (ARBs). Therapy then requires sequentially adding an angiotensin
converting enzyme (ACE) inhibitor to reduce the levels of angiotensin (Ang) II resulting from
blockage of the Ang II receptor and then to administer a beta-blocker to decrease the
elevated renin secretion due to both the ACE inhibitors and ARBs Objective: This study, which
compares two antihypertensive treatment regimens in patients with RH, has the following
objectives: to demonstrate the therapeutic efficacy of SNB against DBB in RH patients, and to
assess the side effects and adherence to treatment over 20 weeks of treatment.
Enrollment: The eligibility criteria will follow those shown in the flowchart for the
diagnosis of RH of the First Brazilian Position on RH.
Patients will be excluded if they have: chronic renal failure, atrial
fibrillation/atrioventricular block, contraindication to the drugs that will be used, refusal
or failure to follow the regimen and secondary hypertension.
Follow-up: Patients will be analyzed in five visits at intervals of 28 days for 20 weeks
Phase:
Phase 4
Details
Lead Sponsor:
Sao Jose do Rio Preto Medical School Sao Jose do Rio Preto University