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Trial record 23 of 112 for:    EPLERENONE

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

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ClinicalTrials.gov Identifier: NCT03476616
Recruitment Status : Not yet recruiting
First Posted : March 26, 2018
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
Konstantinos Tsioufis, Hippocration General Hospital

Tracking Information
First Submitted Date  ICMJE March 19, 2018
First Posted Date  ICMJE March 26, 2018
Last Update Posted Date August 3, 2018
Estimated Study Start Date  ICMJE September 1, 2018
Estimated Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 19, 2018)
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 monitoring 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
Change History Complete list of historical versions of study NCT03476616 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2018)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2018)
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 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
Current Other Pre-specified Outcome Measures
 (submitted: March 25, 2018)
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
Original Other Pre-specified Outcome Measures
 (submitted: March 19, 2018)
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 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
 
Descriptive Information
Brief Title  ICMJE Antihypertensive Pharmacological Therapy With Mineralocorticoid Receptor Antagonists in Obese Hypertensive Patients
Official Title  ICMJE HYpertension Therapy With Valsartan Versus EpleRenone for Obese Patients: A Randomized Clinical Trial
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypertension
  • Obesity
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Eplerenone (-based therapy) arm
  • 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.

    Intervention: Drug: Valsartan (-based therapy) arm
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 19, 2018)
330
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2020
Estimated Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Konstantinos P Tsioufis, Ass. Prof. 6932586087 ext +30 ktsioufis@hippocratio.gr
Contact: Panayiotis P Iliakis, MD 6937489286 ext +30 panayiotisiliakis@gmail.com
Listed Location Countries  ICMJE Greece
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03476616
Other Study ID Numbers  ICMJE Not Provided
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Konstantinos Tsioufis, Hippocration General Hospital
Study Sponsor  ICMJE Hippocration General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Konstantinos P Tsioufis, Ass. Prof. Hypertension Unit, First Cardiology Clinic, Hippocration General Hospital, University of Athens, Greece
PRS Account Hippocration General Hospital
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP