Spironolactone Versus Indapamide in Obese and Hypertensive Patients

P

Peking University

Status

Unknown

Conditions

Hypertension

Treatments

Drug: Indapamide
Drug: Amlodipine
Drug: Spironolactone

Study type

Interventional

Funder types

Other

Identifiers

NCT03626506
BMUJI007

Details and patient eligibility

About

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.

Full 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.

Enrollment

400 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Patients with essential hypertension aged between 18-80years
  • Office systolic blood pressure (SBP)≥140mmHg and <180mmHg without treatment or on one antihypertensive drug or SBP<140mmHg on two antihypertensive drugs
  • Waist circumference ≥90cm for males, ≥ 80cm for females

Exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

400 participants in 2 patient groups

spironolactone
Experimental group
Description:
Subjects will take spironolactone 20~40mg once daily on top of amlodipine 5~10mg once daily.
Treatment:
Drug: Spironolactone
Drug: Amlodipine
indapamide
Active Comparator group
Description:
Subjects will take indapamide 1.5~3.0mg once daily on top of amlodipine 5~10mg once daily.
Treatment:
Drug: Amlodipine
Drug: Indapamide

Trial contacts and locations

1

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Central trial contact

Guisong Wang, MD

Data sourced from clinicaltrials.gov

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