Resistant Hypertension Optimal Treatment (ReHOT)
Recruitment status was: Recruiting
Resistant hypertension (ReHy) is an emerging clinical and public health problem which tends to increase because populations are living longer and there is a growing global epidemic of obesity, diabetes and sleep apnea. It is also tempting to speculate that the excessive dietary salt ingestion reported in many countries can contribute substantially to the risk of ReHy development. ReHy is defined as persistent high blood pressure (above the target goal) in spite of the use of at least 3 antihypertensive agents of different classes, one of them must being diuretics.
Data regarding the exact prevalence of ReHy are very limited. In addition, little data is available about 3-drug combinations but a simplified treatment algorithm has demonstrated that a combination of a diuretic plus an angiotensin-converting enzyme inhibitors (ACEi) or an angiotensin-receptor blocker (ARB) plus diuretic, adding a calcium channel blocker when necessary, controlled 64% of hypertensive patients and, in addition, was even more efficient than the current guideline-based management. By contrast, the fourth drug to be added-on the triple regimen is still controversial and guided by empirical choices or personal preferences. Recent studies suggest the emerging role of spironolactone as the "first-line" fourth drug for treating resistant hypertension. Conversely, because of the pathophysiological rationale, others have proposed the use of β-blockers or even centrally acting agents for managing the sympathetic hyperactivity. The present concerns about the limited blood pressure reducing effect of β-blockers, especially in elderly people, the potent effect of centrally acting agents and our personal experience are pointing to clonidine as the fourth drug to be added-on to a multidrug combination for reaching optimal blood pressure in patients with ReHy. Nevertheless, no studies have been performed comparing, head-to-head, which one is the best fourth drug (spironolactone or clonidine) to be added-on to a common used multidrug combination in order to treat this condition.
Therefore, the principal objectives of the ReHOT Trial are to assess prospectively: (1) the prevalence of ReHy in a cohort of outpatients with stage II hypertension; (2) the effect of spironolactone on blood pressure, in comparison to clonidine, when added to a multidrug combination consisting of chlorthalidone plus ACEi (or ARB) plus amlodipine, all of 3 up-titrated to the highest dose; (3) the role of measuring sympathetic nervous system activity and renin-angiotensin-aldosterone activity on predicting the response of blood pressure to spironolactone and clonidine.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicenter Study of Patients With Hypertension Resistant to Patient Identification and Standardization of Therapeutic|
- Blood pressure (mmHg) [ Time Frame: Patients willl be followed for an expected average of 3 months ] [ Designated as safety issue: Yes ]Compare the effect of spironolactone on blood pressure vs. clonidine, when added to a multidrug combination consisting of chlorthalidone plus ACEi (or ARB) plus amlodipine, all of 3 up-titrated to the highest dose;
- Sympathetic nervous system and renin-angiotensin-aldosterone activity [ Time Frame: At baseline and at the end of the randomization (3 months) ] [ Designated as safety issue: No ]Compare the role of measuring sympathetic nervous system activity and renin-angiotensin-aldosterone activity on predicting the response of blood pressure to spironolactone and clonidine.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||July 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|Active Comparator: Spironolactone||
Spironolactone (titrating dose from 12.5 to 50mg SID)
|Active Comparator: Clonidine||
Clonidine (titrating dose from 0.100-0.300mg BID)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01643434
|University of São Paulo General Hospital|
|São Paulo, Brazil, 05403-000|
|Principal Investigator:||Eduardo M. Krieger, Doctor||University of São Paulo General Hospital|