Resistant Hypertension Optimal Treatment
Information source: Instituto do Coracao
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension
Intervention: Spironolactone (Drug); Clonidine (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Instituto do Coracao Official(s) and/or principal investigator(s): Eduardo M. Krieger, Doctor, Principal Investigator, Affiliation: University of São Paulo General Hospital
Overall contact: Eduardo M. Krieger, Doctor, Phone: +55113069 5048, Email: edkrieger@incor.usp.br
Summary
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.
Clinical Details
Official title: Multicenter Study of Patients With Hypertension Resistant to Patient Identification and Standardization of Therapeutic
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Blood pressure (mmHg)
Secondary outcome: Sympathetic nervous system and renin-angiotensin-aldosterone activity
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria
1. Patients aged between 18 and 75
2. With systolic blood pressure> 160 mmHg and <220mmHg and / or diastolic> 100 mmHg in
the sitting position and according to Brazilian Guidelines on Hypertension (perform
steps by obtaining two consecutive measurements differing by less than 4 mmHg between
them, calibrated using a sphygmomanometer)
3. Patient regularly enrolled in participating center
Exclusion criteria
1. Systolic blood pressure> 220 mmHg
2. Patients with cardiovascular events (stroke, AMI, etc.). or cardiovascular procedures
with less than 6 months of evolution
3. Renal stages IV and V (glomerular20 filtration estimated by MDRD formula <30 ml /
min; where MDRD = 186 x (S_Cr) - 1. 154 x (age) -0. 203 x (0. 742 if fem.) x (1. 210 if
Afro-amer. ))
4. Heart failure class III and IV
5. History of malignant disease with life expectancy < 2 years
6. Alcoholism
7. Psychiatric illnesses that prevent compliance with the Protocol
8. Women of childbearing age who are not in use of effective contraception
9. Pregnancy
10. Arrhythmias, valvular heart disease, AV block 2 and 3 degrees without MP
11. Hepatic impairment
12. Patients with a history of hypersensitivity to any of the drugs under study
13. Examination of the fundus: Grade III and Grade IV
Locations and Contacts
Eduardo M. Krieger, Doctor, Phone: +55113069 5048, Email: edkrieger@incor.usp.br
University of São Paulo General Hospital, São Paulo 05403-000, Brazil; Recruiting Eduardo M. krieger, Doctor, Phone: +55113069-5048, Email: edkrieger@incor.usp.br Jose E. krieger, Doctor, Phone: +55113069 5068, Email: zecakrieger@gmail.com Eduardo M. Krieger, Doctor, Principal Investigator
Additional Information
Starting date: August 2012
Last updated: June 6, 2013
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