Spironolactone Versus Indapamide in Obese and Hypertensive Patients

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.

Conditions

• Hypertension

Interventions

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

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.

Sponsors & Collaborators

• University of Michigan

  collaborator OTHER

• Peking University

  collaborator OTHER

• Peking University Third Hospital

  lead OTHER

Principal Investigators

• Wang Guisong, MD · Peking University Third Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-02-13

Primary Completion

2020-08-31

Completion

2020-12-31

Countries

• China

Study Locations