Resistant Hypertension Optimal Treatment
ReHOT
Multicenter Study of Patients With Hypertension Resistant to Patient Identification and Standardization of Therapeutic
1 other identifier
interventional
2,000
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 hypertension
Started Aug 2012
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 11, 2012
CompletedFirst Posted
Study publicly available on registry
July 18, 2012
CompletedStudy Start
First participant enrolled
August 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2014
CompletedJune 7, 2013
June 1, 2013
1.3 years
July 11, 2012
June 6, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Blood pressure (mmHg)
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;
Patients willl be followed for an expected average of 3 months
Secondary Outcomes (1)
Sympathetic nervous system and renin-angiotensin-aldosterone activity
At baseline and at the end of the randomization (3 months)
Study Arms (2)
Spironolactone
ACTIVE COMPARATORClonidine
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Patients aged between 18 and 75
- 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)
- Patient regularly enrolled in participating center
You may not qualify if:
- Systolic blood pressure\> 220 mmHg
- Patients with cardiovascular events (stroke, AMI, etc.). or cardiovascular procedures with less than 6 months of evolution
- 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. ))
- Heart failure class III and IV
- History of malignant disease with life expectancy \< 2 years
- Alcoholism
- Psychiatric illnesses that prevent compliance with the Protocol
- Women of childbearing age who are not in use of effective contraception
- Pregnancy
- Arrhythmias, valvular heart disease, AV block 2 and 3 degrees without MP
- Hepatic impairment
- Patients with a history of hypersensitivity to any of the drugs under study
- Examination of the fundus: Grade III and Grade IV
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of São Paulo General Hospital
São Paulo, São Paulo, 05403-000, Brazil
Related Publications (2)
Krieger EM, Drager LF, Giorgi DMA, Pereira AC, Barreto-Filho JAS, Nogueira AR, Mill JG, Lotufo PA, Amodeo C, Batista MC, Bodanese LC, Carvalho ACC, Castro I, Chaves H, Costa EAS, Feitosa GS, Franco RJS, Fuchs FD, Guimaraes AC, Jardim PC, Machado CA, Magalhaes ME, Mion D Jr, Nascimento RM, Nobre F, Nobrega AC, Ribeiro ALP, Rodrigues-Sobrinho CR, Sanjuliani AF, Teixeira MDCB, Krieger JE; ReHOT Investigators. Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment). Hypertension. 2018 Apr;71(4):681-690. doi: 10.1161/HYPERTENSIONAHA.117.10662. Epub 2018 Feb 20.
PMID: 29463627DERIVEDReHOT Investigators; Krieger EM, Drager LF, Giorgi DM, Krieger JE, Pereira AC, Barreto-Filho JA, da Rocha Nogueira A, Mill JG. Resistant hypertension optimal treatment trial: a randomized controlled trial. Clin Cardiol. 2014 Jan;37(1):1-6. doi: 10.1002/clc.22228. Epub 2013 Dec 11.
PMID: 24338935DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Eduardo M. Krieger, Doctor
University of São Paulo General Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER GOV
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- PI
Study Record Dates
First Submitted
July 11, 2012
First Posted
July 18, 2012
Study Start
August 1, 2012
Primary Completion
December 1, 2013
Study Completion
July 1, 2014
Last Updated
June 7, 2013
Record last verified: 2013-06