Resistant Hypertension Optimal Treatment (ReHOT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Instituto do Coracao
Sponsor:
Collaborator:
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Information provided by (Responsible Party):
Eduardo Moacyr Krieger, Instituto do Coracao
ClinicalTrials.gov Identifier:
NCT01643434
First received: July 11, 2012
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Spironolactone
Drug: Clonidine
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Instituto do Coracao:

Primary Outcome Measures:
  • 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;


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 2000
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)
Arms Assigned Interventions
Active Comparator: Spironolactone Drug: Spironolactone
Spironolactone (titrating dose from 12.5 to 50mg SID)
Active Comparator: Clonidine Drug: Clonidine
Clonidine (titrating dose from 0.100-0.300mg BID)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01643434

Contacts
Contact: Eduardo M. Krieger, Doctor +55113069 5048 edkrieger@incor.usp.br
Contact: Jose E. Krieger, Doctor +55113069-5068 zecakrieger@gmail.com

Locations
Brazil
University of São Paulo General Hospital Recruiting
São Paulo, Brazil, 05403-000
Contact: Eduardo M. krieger, Doctor    +55113069-5048    edkrieger@incor.usp.br   
Contact: Jose E. krieger, Doctor    +55113069 5068    zecakrieger@gmail.com   
Principal Investigator: Eduardo M. Krieger, Doctor         
Sponsors and Collaborators
Instituto do Coracao
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Investigators
Principal Investigator: Eduardo M. Krieger, Doctor University of São Paulo General Hospital
  More Information

No publications provided by Instituto do Coracao

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eduardo Moacyr Krieger, PI, Instituto do Coracao
ClinicalTrials.gov Identifier: NCT01643434     History of Changes
Other Study ID Numbers: 0758/09
Study First Received: July 11, 2012
Last Updated: June 6, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Instituto do Coracao:
Resistant Hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Spironolactone
Clonidine
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014