NCT02832973: ResHypOT

Resistant Hypertension On Treatment - Sequential Nephron Blockade Compared to Dual Blockade of the Renin-angiotensin-aldosterone System Plus Bisoprolol in the Treatment of Resistant Arterial Hypertension: A Randomized Trial (ResHypOT)

Completed Phase 4 Last updated 3 April 2019

What this trial tests

Phase 4 trial testing Spironolactone in Hypertension Resistant to Conventional Therapy in 72 participants. Completed in 1 March 2018.

Timeline

1 September 2015

Primary endpoint
1 December 2017

1 March 2018

Quick facts

Lead sponsor	Sao Jose do Rio Preto Medical School
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	72
Start date	1 September 2015
Primary completion	1 December 2017
Estimated completion	1 March 2018
Sites	1 location across Brazil

Drugs / interventions tested

• Spironolactone (spironolactone) — full drug profile →
• Furosemide,
• Amiloride (AMILORIDE) — full drug profile →
• Ramipril (RAMIPRIL) — full drug profile →
• Bisoprolol (BISOPROLOL) — full drug profile →

Conditions studied

• Hypertension Resistant to Conventional Therapy — all drugs for Hypertension Resistant to Conventional Therapy →

Sponsor

Sao Jose do Rio Preto Medical School

Who can join

Adults 18 to 70, any sex, with Hypertension Resistant to Conventional Therapy. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Reduction of Systolic BP, diastolic BP, mean BP and pulse pressure levels will be used to compare sequential nephron blockade versus dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol
  Time frame: Twenty weeks
  Systolic BP (mmHg), Diastolic BP (mmHg), Mean BP (mmHg) and Pulse Pressure (mmHg)

Sponsor's own description

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

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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).
   Cestario EDES, Vilela-Martin JF, Cosenso-Martin LN, Rubio TA, et al · · 2022 · cited 4× · PMID 36545494 · DOI 10.2147/vhrm.s383007
2. 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.
   Cestário EDES, Fernandes LAB, Giollo-Júnior LT, Uyemura JRR, et al · · 2018 · cited 3× · PMID 29433578 · DOI 10.1186/s13063-017-2343-3
3. Effects of different antihypertensive drug classes on central and ambulatory blood pressure in resistant hypertension: A randomized clinical trial.
   Yugar-Toledo JC, Minari TP, de Mello PG, do Espirito Santo Cestario E, et al · · 2026 · cited 1× · PMID 40859651 · DOI 10.1002/bcp.70249