Resistant Hypertension Optimal Treatment (ReHOT)

June 6, 2013 updated by: Eduardo Moacyr Krieger, Instituto do Coracao

Multicenter Study of Patients With Hypertension Resistant to Patient Identification and Standardization of Therapeutic

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 Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

2000

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 05403-000
        • Recruiting
        • University of Sao Paulo General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Eduardo M. Krieger, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood pressure (mmHg)
Time Frame: Patients willl be followed for an expected average of 3 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sympathetic nervous system and renin-angiotensin-aldosterone activity
Time Frame: At baseline and at the end of the randomization (3 months)
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.
At baseline and at the end of the randomization (3 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto do Coracao

Collaborators

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Investigators

  • Principal Investigator: Eduardo M. Krieger, Doctor, University of Sao Paulo General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (ANTICIPATED)

December 1, 2013

Study Completion (ANTICIPATED)

July 1, 2014

Study Registration Dates

First Submitted

July 11, 2012

First Submitted That Met QC Criteria

July 16, 2012

First Posted (ESTIMATE)

July 18, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

June 7, 2013

Last Update Submitted That Met QC Criteria

June 6, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0758/09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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