Antihypertensive Pharmacological Therapy With Mineralocorticoid Receptor Antagonists in Obese Hypertensive Patients (HEVRO)

August 2, 2018 updated by: Konstantinos Tsioufis, Hippocration General Hospital

HYpertension Therapy With Valsartan Versus EpleRenone for Obese Patients: A Randomized Clinical Trial

Obesity is a complex metabolic state at which many pathophysiological pathways seem to interfere, like imbalance of autonomic nervous system, as well as renin-angiotensin-aldosterone system (RAAS) activation. Latest studies have shown that the increase of peripheral fat in obese patients, alongside with the increase of P-450 aromatase leads to hyper-aldosteronism, which results to increased sodium intake and rise of blood pressure. The present study aims to investigate the potential superiority of an aldosterone antagonist based therapy (eplerenone) over the renin-angiotensin antagonists (ARBs) (valsartan) based therapy in hypertensive obese patients regarding reduction of blood pressure (office, home and ambulatory) over a 24-week period.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The present study plans to enroll obese patients (BMI= 30-40 kg/m2) of 30-75 years of age, with untreated or never-treated essential hypertension to either eplerenone-based or valsartan-based therapy Patients visiting hypertension center(s), eligible to participate in the study and meeting study's inclusion criteria, will at first thoroughly be informed of study's protocol rationale, including scheduled follow-up visits. There will be a period of 2-4 weeks, at which medical history will be taken, as well as somatometrics, including height, weight, BMI and waist circumference. Moreover, a thorough clinical examination will take place, including office blood pressure, ECG, heart-echo, renal ultrasound, blood and urine ultrasound. All women of gestational age should have pregnancy test.

At randomization visit, patients still meeting inclusion/exclusion criteria will be randomized (1:1) to either eplerenone (E) 25mg bd or valsartan (V) 160mg od for 8 weeks. At 8, 16 and 24 weeks, patients at both arms will be evaluated with ambulatory BP measurements primary, as well as home and office BP measurements. At week 8, patients with controlled hypertension (mean ambulatory blood pressure measurement (ABPM) <130/80mmHg), will continue in monotherapy with eplerenone or valsartan and patients with uncontrolled hypertension (mean 24-h ambulatory≥130/80mmHg) will continue with the addition of calcium-channel blocker, amlodipine (C) 5 mg od. At week 16, patients achieving BP control will continue in either monotherapy (E), (V) or dual therapy (E+C), (V+C). However, in patients not achieving blood pressure target, a third drug, thiazide-like-diuretic will be added [indapamide (D) 1.25 mg od]. All groups at both arms will be finally evaluated at 24 weeks.

Study Type

Interventional

Enrollment (Anticipated)

330

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 Contact

Study Contact Backup

Study Locations

  • Greece
      • Athens, Greece, 11527
        • Hypertension Unit, First Cardiology Clinic, Hippocration General Hospital, University of Athens, Athens, Greece
        • Contact:
        • Contact:
        • Principal Investigator:
          • Konstantinos P Tsioufis, Ass. Prof.
        • Sub-Investigator:
          • Kyriakos S Dimitriadis, MD, PhD
        • Sub-Investigator:
          • Panayiotis P Iliakis, MD

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

28 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 30-75 years of age
  2. Written consent
  3. Untreated or never-treated arterial hypertension with office systolic blood pressure of 140-180 mmHg and/or diastolic blood pressure of 90-120 mmHg, confirmed by 24-hour ambulatory blood pressure measurements of mean ambulatory systolic blood pressure over 130 mmHg and/or mean ambulatory diastolic blood pressure over 80 mmHg
  4. Obesity, confirmed estimated by Body Mass Index (BMI) of 30-40 kg/m2

Exclusion Criteria

  1. Age <30 or >75
  2. Inability to give informed consent
  3. Participation in a clinical study involving an investigational drug or device within 4 weeks of screening
  4. Secondary hypertension
  5. Recent (<6 months) cardiovascular event requiring hospitalization (eg. myocardial infarction or stroke)
  6. Type 1 diabetes
  7. Chronic kidney disease assessed by Estimated Glomerular Filtration Rate (eGFR) <45 mL/min
  8. Bilateral renal arteries stenosis
  9. Addison's disease
  10. Hemodynamically significant valvular heart disease
  11. Plasma potassium outside of normal range on two successive measurements during screening
  12. Pregnancy, planning to conceive or women of childbearing potential, that is, not using effective contraception
  13. Scheduled surgery or cardiovascular surgery over the next 6 months
  14. Absolute contra-indication to study drugs (eg. asthma) or previous intolerance of trial therapy
  15. History of sustained atrial fibrillation
  16. Requirement for study drug for reason other than to treat hypertension, (eg, β-blockers for angina or aldosterone antagonists for heart failure)
  17. Neoplasm under treatment (radiotherapy / chemotherapy / immunotherapy)
  18. Any concomitant condition that, in the opinion of the investigator, may adversely affect the safety and/or efficacy of the study drug or
  19. severely limit that patients' life-span or ability to complete the study (eg, alcohol or drug abuse, disabling or terminal illness, mental
  20. disorders)
  21. Contemporary systemic disease with life expectancy shorter than the end of the study

  22. Treatment with any of the following medications:

    • Oral corticosteroids within 3 months of screening. Treatment with systemic corticosteroids is also prohibited during study participation
    • Chronic stable use, or unstable use of NSAIDs (other than low dose aspirin) is prohibited. Chronic use is defined as >3 consecutive or non-consecutive days of treatment per week. In addition, intermittent use of NSAIDs is strongly discouraged throughout the study and NSAIDs if required, must not be used for more than a total of 2 days. For those requiring analgesics during the study, paracetamol is recommended.
    • The use of short-acting nitrates (eg, sublingual nitroglycerin) is permitted.
    • The use of sympathomimetic decongestants is permitted, however, not within 1 day prior to any study visit/BP assessment
    • The use of theophylline is permitted but the dose must be stable for at least 4 weeks prior to screening and throughout the study;
    • The use of phosphodiesterase type V inhibitors is permitted; however, study participants must refrain from taking these medications for at least 1 day prior to screening or any subsequent study visits
    • The use of α-blockers is not permitted, with the exception of alfuzosin and tamsulosin for prostatic symptoms

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Eplerenone (-based therapy) arm

Obese pts with hypertension, starting treatment with eplerenone 25mg twice daily (BD). ABPM wil be scheduled at wks 8, 16 and 24.

At wk 8 if mean ABPM < 130/80mm Hg will continue to monotherapy with eplerenone. If not controlled (mean ABPM > 130/80mm Hg) at wk8, amlodipine 5mg OD will be added.

At wk 16 if mean ABPM < 130/80mm Hg will continue to monotherapy with eplerenone, or dual therapy with eplerenone and amlodipine. If not controlled (mean ABPM > 130/80mm Hg) at wk16, indapamide 1,5mg OD will be added. All patients will be followed up for 24 weeks.
Drug: Eplerenone (-based therapy) arm
At randomization, pts meeting inclusion/exclusion criteria will be randomized (1:1) to either eplerenone (E) 25mg bd or valsartan (V) 160mg od for 8 wks. At 8, 16 and 24 wks, pts at both arms will be evaluated with ABPM primary, as well as home and office BP measurements. At wk 8, pts with controlled hypertension (mean ABPM <130/80mmHg), will continue in monotherapy with eplerenone or valsartan and pts with uncontrolled hypertension (mean ABPM ≥130/80mmHg) will continue with the addition of amlodipine (C) 10mg od. At wk 16, pts achieving BP control will continue in either monotherapy (E), (V) or dual therapy (E+C), (V+C). However, in pts not achieving ABPM target, a third drug, will be added [indapamide (D) 1.25 mg od]. All groups at both arms will be evaluated at 24 wks by ABPM.
Active Comparator: Valsartan (-based therapy) arm

Obese pts with hypertension, starting treatment with valsartan 160mg once daily (OD). ABPM wil be scheduled at wks 8, 16 and 24.

At wk 8 if mean ABPM < 130/80mm Hg will continue to monotherapy with valsartan. If not controlled (mean ABPM > 130/80mm Hg) at wk8, amlodipine 5mg OD will be added.

At wk 16 if mean ABPM < 130/80mm Hg will continue to monotherapy with valsartan, or dual therapy with valsartan and amlodipine. If not controlled (mean ABPM > 130/80mm Hg) at wk16, indapamide 1,5mg OD will be added. All patients will be followed up for 24 weeks.
Drug: Valsartan (-based therapy) arm
At randomization, pts meeting inclusion/exclusion criteria will be randomized (1:1) to either eplerenone (E) 25mg bd or valsartan (V) 160mg od for 8 wks. At 8, 16 and 24 wks, pts at both arms will be evaluated with ABPM primary, as well as home and office BP measurements. At wk 8, pts with controlled hypertension (mean ABPM <130/80mmHg), will continue in monotherapy with eplerenone or valsartan and pts with uncontrolled hypertension (mean ABPM ≥130/80mmHg) will continue with the addition of amlodipine (C) 10mg od. At wk 16, pts achieving BP control will continue in either monotherapy (E), (V) or dual therapy (E+C), (V+C). However, in pts not achieving ABPM target, a third drug, will be added [indapamide (D) 1.25 mg od]. All groups at both arms will be evaluated at 24 wks by ABPM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in change of ABPM from baseline, in the eplerenone arm versus the valsartan arm as monotherapy at 8 weeks, as combined dual treatment with amlodipine at 16 weeks and as combined triple treatment with amlodipine and indapamide at 24 weeks.
Time Frame: 8, 16 and 24 weeks
Ambulatory blood pressure measurements (metric unit: mmHg) at baseline and 8,16 and 24 weeks and evaluation of the difference of mean ambulatory systolic and diastolic blood pressure measurements between baseline and each time frame in all participants
8, 16 and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in change of office BP from baseline, in the eplerenone arm versus the valsartan arm as monotherapy at 8 weeks, as combined dual treatment with amlodipine at 16 weeks and as combined triple treatment with amlodipine and indapamide at 24 weeks.
Time Frame: 8, 16 and 24 weeks
Office blood pressure measurements (metric unit: mmHg) at baseline and 8,16 and 24 weeks and evaluation of the difference of office systolic and diastolic blood pressure measurements between baseline and each time frame in all participants
8, 16 and 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in frequency of controlled hypertension (mean ABPM < 130/80 mm Hg) between the study arms at 8, 16 and 24 weeks.
Time Frame: 8, 16 and 24 weeks
Ambulatory blood pressure monitoring (metric unit: mmHg) at baseline and 8,16 and 24 weeks and evaluation of the difference of mean ambulatory systolic and diastolic blood pressure measurements between baseline and each time frame in all participants
8, 16 and 24 weeks

Collaborators and Investigators

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

Sponsor

Hippocration General Hospital

Investigators

  • Principal Investigator: Konstantinos P Tsioufis, Ass. Prof., Hypertension Unit, First Cardiology Clinic, Hippocration General Hospital, University of Athens, Greece

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 (Anticipated)

September 1, 2018

Primary Completion (Anticipated)

September 1, 2020

Study Completion (Anticipated)

September 1, 2020

Study Registration Dates

First Submitted

March 19, 2018

First Submitted That Met QC Criteria

March 19, 2018

First Posted (Actual)

March 26, 2018

Study Record Updates

Last Update Posted (Actual)

August 3, 2018

Last Update Submitted That Met QC Criteria

August 2, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

Clinical Trials on Hypertension

Clinical Trials on Eplerenone (-based therapy) arm

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uganda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe