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Trial record 100 of 112 for:    EPLERENONE

Spironolactone Versus Indapamide in Obese and Hypertensive Patients

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ClinicalTrials.gov Identifier: NCT03626506
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : April 26, 2019
Sponsor:
Collaborators:
University of Michigan
Peking University
Information provided by (Responsible Party):
Peking University Third Hospital

Brief Summary:
Most recent guidelines continue to recommend thiazide diuretics as first-line agents for patients with hypertension in spite of the potential metabolic side effects, while mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone, are mainly recommended to be used in patients with resistant hypertension or heart failure.However,animal studies demonstrated that MRAs induce beneficial changes in left ventricular remodeling and prevent or partially reverse cardiac fibrosis and pathological hypertrophy that contribute to the development of diastolic heart failure. MRAs have also been shown to decrease inflammation and myocardial fibrosis in patients with obesity and the metabolic syndrome. In the proposed study, the investigators planned to randomize 400 patients with essential hypertension and increased waist circumference to receive spironolactone or indapamide in combination with amlodipine for 12 months. The effects of the two diuretics on target organ damage detected by changes in left atrial volume index(LAVI) by echocardiography reflecting left ventricular diastolic dysfunction or changes in carotid-femoral pulse wave velocity(PWV) reflecting arterial stiffness will be compared. The potential role of MRAs as initial therapy for patients with essential hypertension and visceral obesity will be evaluated.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Spironolactone Drug: Indapamide Drug: Amlodipine Not Applicable

Detailed Description:
Thiazide diuretics have been widely used for the management of essential hypertension, especially in patients with salt-sensitive hypertension. Most recent guidelines continue to recommend thiazide diuretics as first-line agents for all patients with hypertension in spite of the potential metabolic side effects such as hypokalemia, hypertriglyceridemia, impaired glucose tolerance and increases in serum cholesterol and uric acid. However, mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone, are mainly recommended to be used in patients with resistant hypertension or heart failure because they have never been evaluated for efficacy in reducing cardiovascular events in uncomplicated patients with hypertension. Indeed, it has been demonstrated that MRAs reduced total mortality or cardiovascular death in patients with systolic heart failure with severe or mild symptoms and in patients undergoing hemodialysis for chronic renal dysfunction. Animal studies demonstrated that MRAs induce beneficial changes in left ventricular remodeling and prevent or partially reverse cardiac fibrosis and pathological hypertrophy that contribute to the development of diastolic heart failure. MRAs have also been shown to decrease inflammation and myocardial fibrosis in patients with obesity and the metabolic syndrome. Of interest is the recent finding in EMPHASIS-HF study in which almost all of the benefit of eplerenone was found in those patients with an increased waist circumference. Therefore, the investigators have reason to believe that MRAs will be more effective than thiazide diuretics in preventing target organ damage and can be used initially in patients with essential hypertension and visceral obesity. In the proposed study, the investigators planned to randomize 400 patients with essential hypertension and increased waist circumference to receive spironolactone or indapamide in combination with amlodipine for 12 months. The effects of the two diuretics on target organ damage detected by changes in left atrial volume index(LAVI) by echocardiography reflecting left ventricular diastolic dysfunction or changes in carotid-femoral pulse wave velocity(PWV) reflecting arterial stiffness will be compared. If it proves that spironolactone as first-line antihypertensive medication is more effective than indapamide in target organ protection, the investigators would propose a large scale cardiovascular outcome trial to evaluate cardiovascular events in patients with essential hypertension and visceral obesity.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized, controlled, open-label trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of spironolactoNe Versus Indapamide on Target Organ Damage in Patients With Obesity and hYpertension(ENVOY)
Actual Study Start Date : February 13, 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: spironolactone
Subjects will take spironolactone 20~40mg once daily on top of amlodipine 5~10mg once daily.
Drug: Spironolactone
After a 2-week run-in period on amlodipine, patients who still have SBP ≥ 140mmHg will take spironolactone 20mg once daily on top of amlodipine for 12 months. During the first two months after randomization, spironolactone can be titrated to 40mg if office SBP remains ≥ 140mmHg.

Drug: Amlodipine
After a 2-week run-in period on amlodipine 5mg once daily, patients who still have SBP ≥ 140mmHg will be randomized to add spironolactone 20mg once daily or extended-release indapamide 1.5mg once daily to amlodipine for 12 months. During the first two months after randomization, amlodipine can be titrated to 10mg if office SBP remains ≥ 140mmHg.

Active Comparator: indapamide
Subjects will take indapamide 1.5~3.0mg once daily on top of amlodipine 5~10mg once daily.
Drug: Indapamide
After a 2-week run-in period on amlodipine, patients who still have SBP ≥ 140mmHg will take extended-release indapamide 1.5mg once daily on top of amlodipine for 12 months. During the first two months after randomization, indapamide can be titrated to 3mg if office SBP remains ≥ 140mmHg.

Drug: Amlodipine
After a 2-week run-in period on amlodipine 5mg once daily, patients who still have SBP ≥ 140mmHg will be randomized to add spironolactone 20mg once daily or extended-release indapamide 1.5mg once daily to amlodipine for 12 months. During the first two months after randomization, amlodipine can be titrated to 10mg if office SBP remains ≥ 140mmHg.




Primary Outcome Measures :
  1. left atrial volume index (LAVI) [ Time Frame: 12 months ]
    change in left atrial volume index (LAVI) from baseline to the end of study period of 12 months


Secondary Outcome Measures :
  1. carotid-femoral pulse wave velocity (PWV) [ Time Frame: 12 months ]
    change in carotid-femoral pulse wave velocity (PWV) from baseline to the end of study period of 12 months



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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with essential hypertension aged between 50-80years
  2. Office systolic blood pressure (SBP)≥140mmHg and <180mmHg without treatment or on one antihypertensive drug or SBP<140mmHg on two antihypertensive drugs
  3. Waist circumference ≥90cm for males, ≥ 80cm for females

Exclusion Criteria:

  1. Secondary hypertension.
  2. Symptomatic congestive heart failure or history of heart failure.
  3. History of ischemic stroke, unstable angina or myocardial infarction;
  4. Atrial fibrillation
  5. Serum creatinine ≥ 2.0mg/dl or eGFR≤ 30 ml/min/1.73 m2
  6. Serum K+ ≥ 5.0 mmol/L or ≤3.5 mmol/L
  7. Type 2 diabetes.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03626506


Contacts
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Contact: Guisong Wang, MD 86-13701070359 guisongwang2007@hotmail.com

Locations
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China, Beijing
Peking University Third Hospital Recruiting
Beijing, Beijing, China, 100191
Contact: Guisong Wang, MD    86-13701070359    guisongwang2007@hotmail.com   
Sponsors and Collaborators
Peking University Third Hospital
University of Michigan
Peking University
Investigators
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Principal Investigator: Wang Guisong, MD Peking University Third Hospital

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Responsible Party: Peking University Third Hospital
ClinicalTrials.gov Identifier: NCT03626506     History of Changes
Other Study ID Numbers: BMUJI007
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peking University Third Hospital:
spironolactone
Indapamide
Obesity
Hypertension
Target organ damage
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Indapamide
Spironolactone
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors