- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03626506
Spironolactone Versus Indapamide in Obese and Hypertensive Patients
December 1, 2019 updated by: Peking University Third Hospital
Evaluation of spironolactoNe Versus Indapamide on Target Organ Damage in Patients With Obesity and hYpertension(ENVOY)
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
400
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Guisong Wang, MD
- Phone Number: 86-13701070359
- Email: guisongwang2007@hotmail.com
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100191
- Recruiting
- Peking University Third Hospital
-
Contact:
- Guisong Wang, MD
- Phone Number: 86-13701070359
- Email: guisongwang2007@hotmail.com
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: spironolactone
Subjects will take spironolactone 20~40mg once daily on top of amlodipine 5~10mg once daily.
|
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.
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.
|
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Wang Guisong, MD, Peking University Third Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 13, 2019
Primary Completion (Anticipated)
August 1, 2020
Study Completion (Anticipated)
December 1, 2020
Study Registration Dates
First Submitted
August 3, 2018
First Submitted That Met QC Criteria
August 3, 2018
First Posted (Actual)
August 13, 2018
Study Record Updates
Last Update Posted (Actual)
December 3, 2019
Last Update Submitted That Met QC Criteria
December 1, 2019
Last Verified
April 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Hypertension
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Hormone Antagonists
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Mineralocorticoid Receptor Antagonists
- Diuretics, Potassium Sparing
- Sodium Chloride Symporter Inhibitors
- Amlodipine
- Spironolactone
- Indapamide
Other Study ID Numbers
- BMUJI007
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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