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Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT)

This study is currently recruiting participants.
Verified September 2017 by Juan Carlos Yugar Toledo, Sao Jose do Rio Preto Medical School
Sponsor:
ClinicalTrials.gov Identifier:
NCT02832973
First Posted: July 14, 2016
Last Update Posted: October 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Juan Carlos Yugar Toledo, Sao Jose do Rio Preto Medical School
  Purpose

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


Condition Intervention Phase
Hypertension Resistant to Conventional Therapy Drug: Spironolactone Drug: Furosemide, Drug: Amiloride Drug: Ramipril Drug: Bisoprolol Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Juan Carlos Yugar Toledo, Sao Jose do Rio Preto Medical School:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • Electrolytes changes: Sodium, Potassium Chlorine after 20 weeks of treatment with sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol [ Time Frame: Twenty weeks ]
    Sodium (reference: 135-145 mmol/L), potassium (reference: 3.5-5.0 mmol/L) and chlorine (reference: 96-106 mEq/L)

  • Reduction of creatinine clearance after 20 weeks of treatment with sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol [ Time Frame: Twenty weeks ]
    Creatinine clearance (reference - Male: 97 to 137 mL/min and Female: 88 to 128 mL/min)

  • Hypotension [ Time Frame: Twenty weeks ]
    Recognition of hypotension (ABPM - mmHg)


Estimated Enrollment: 80
Study Start Date: September 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Spironolactone, Furosemide Amiloride
Spironolactone 25 mg qd, Furosemide 20 mg qd, Furosemide 40 mg qd, Amiloride 5 mg qd
Drug: Spironolactone
Spironolactone 25 mg
Other Name: Natriuretic diuretics
Drug: Furosemide,
Furosemide 20-40 mg
Other Name: Furosemide 20-40 mg
Drug: Amiloride
Amiloride 5 mg
Other Name: Amiloride 5 mg
Active Comparator: Ramipril, Bisoprolol
Ramipril 5 mg qd, Ramipril 10 mg qd, Bisoprolol 5 mg qd, Bisoprolol 10 mg qd
Drug: Ramipril
Ramipril 5-10 mg
Other Name: ACE inhibitor
Drug: Bisoprolol
Bisoprolol 5-10 mg
Other Name: Betablocker

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Clinical diagnosis of Resistant Hypertension Must to able swallow antihypertensive drug classes at maximum tolerated doses.

Exclusion Criteria:

Secondary Hypertension Chronic renal failure Coronary artery disease Atrial fibrillation Atrioventricular block Refuse or fail to follow regimen

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02832973


Contacts
Contact: Juan C Yugar-Toledo, MD, PhD +55-17-32271899 yugarjuan@uol.com.br
Contact: Elizabeth ES Cestario, MD +55-17-997186562 cestario@cardiol.br

Locations
Brazil
Juan Carlos Yugar-Toledo Recruiting
São José do Rio Preto, São Paulo, Brazil, 15090000
Contact: Juan C Yugar-Toledo, MD, PhD    +55-17-32271899    yugarjuan@uol.com.br   
Contact: Elizabeth DE Cestario, MD    +55-17-997186562    cesatrio@cardiol.br   
Sponsors and Collaborators
Sao Jose do Rio Preto Medical School
Investigators
Study Chair: Juan C Yugar-Toledo, MD, PhD Sao Jose do Rio Preto Medical School
  More Information

Publications:

Responsible Party: Juan Carlos Yugar Toledo, MD, PhD, Sao Jose do Rio Preto Medical School
ClinicalTrials.gov Identifier: NCT02832973     History of Changes
Other Study ID Numbers: SaoJoseRPU
First Submitted: June 12, 2016
First Posted: July 14, 2016
Last Update Posted: October 4, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Juan Carlos Yugar Toledo, Sao Jose do Rio Preto Medical School:
Hypertension Resistant to Conventional Therapy
Natriuretic Agents
Renin-Angiotensin System
Bisoprolol

Additional relevant MeSH terms:
Hypertension
Coronary Vasospasm
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Myocardial Ischemia
Heart Diseases
Furosemide
Spironolactone
Amiloride
Ramipril
Bisoprolol
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antihypertensive Agents
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists