Spironolactone Versus Indapamide in Obese and Hypertensive Patients

NCT ID: NCT03626506

Last Updated: 2019-12-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-13
• Study Completion Date: 2020-12-31

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.

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

spironolactone

Subjects will take spironolactone 20\~40mg once daily on top of amlodipine 5\~10mg once daily.

Group Type: EXPERIMENTAL

Spironolactone

Intervention Type: DRUG

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.

Amlodipine

Intervention Type: DRUG

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.

indapamide

Subjects will take indapamide 1.5\~3.0mg once daily on top of amlodipine 5\~10mg once daily.

Group Type: ACTIVE_COMPARATOR

Indapamide

Intervention Type: DRUG

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.

Amlodipine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with essential hypertension aged between 18-80years

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: collaborator

Peking University Third Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wang Guisong, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Third Hospital

Locations

Peking University Third Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Guisong Wang, MD

Role: CONTACT

guisongwang2007@hotmail.com

86-13701070359

Facility Contacts

Guisong Wang, MD

Role: primary

guisongwang2007@hotmail.com

86-13701070359

Other Identifiers

BMUJI007

Identifier Type: -

Identifier Source: org_study_id