Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT)
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|ClinicalTrials.gov Identifier: NCT02832973|
Recruitment Status : Recruiting
First Posted : July 14, 2016
Last Update Posted : October 4, 2017
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 or disease||Intervention/treatment||Phase|
|Hypertension Resistant to Conventional Therapy||Drug: Spironolactone Drug: Furosemide, Drug: Amiloride Drug: Ramipril Drug: Bisoprolol||Phase 4|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||September 2015|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||March 2018|
Experimental: Spironolactone, Furosemide Amiloride
Spironolactone 25 mg qd, Furosemide 20 mg qd, Furosemide 40 mg qd, Amiloride 5 mg qd
Spironolactone 25 mg
Other Name: Natriuretic diuretics
Furosemide 20-40 mg
Other Name: Furosemide 20-40 mg
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
Ramipril 5-10 mg
Other Name: ACE inhibitor
Bisoprolol 5-10 mg
Other Name: Betablocker
- 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)
- 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)
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
|Contact: Juan C Yugar-Toledo, MD, PhDemail@example.com|
|Contact: Elizabeth ES Cestario, MDfirstname.lastname@example.org|
|Juan Carlos Yugar-Toledo||Recruiting|
|São José do Rio Preto, São Paulo, Brazil, 15090000|
|Contact: Juan C Yugar-Toledo, MD, PhD +55-17-32271899 email@example.com|
|Contact: Elizabeth DE Cestario, MD +55-17-997186562 firstname.lastname@example.org|
|Study Chair:||Juan C Yugar-Toledo, MD, PhD||Sao Jose do Rio Preto Medical School|