Back to resultsEffect of MRA on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia (EMRACHH)
Primary Purpose
Hypertension, Hyperaldosteronaemia
Status
Enrolling by invitation
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Mineralocorticoid Receptor Antagonists(MRAs)
Blank control
Sponsored by
About this trial
This is an interventional prevention trial for Hypertension
Eligibility Criteria
Inclusion Criteria: Age: 18-75 years old; Blood pressure ≥140/90 mmHg, or have taken antihypertensive drugs; Plasma aldosterone concentration> 12ng/ dL; Serum potassium < 4.8mmol/L; Signed the written informed consent. Exclusion Criteria: SBP/DBP≥190/120mmHg, DBP<60 mmHg; Known secondary cause of hypertension, including pheochromocytoma, primary aldosteronism (adrenal tumor > 1cm), Cushing's syndrome, renal artery stenosis, renin tumor, connotation of aorta, etc.; History of ischemic or hemorrhagic stroke within the last 3 months (not lacunar infarction and transient ischemic attack [TIA]). History of Hospitalization for myocardial infarction or unstable angina, or coronary revascularization (PCI or CABG) within the last 3 months. History of aortic dissection/dissection aneurysm rupture. History of NYHA Grade III-IV heart failure or hospitalization Aggravated chronic heart failure upon admission within the last 3 months. A history of persistent atrial fibrillation, atrial flutter, or other severe arrhythmias on admission (including sinus delay, diseased sinus, high atrioventricular block, frequent ventricular morning, etc.). Severe liver disease or liver dysfunction: AST, ALT, or ALP > 5ULN (5 times the upper limit of normal), or BIL > 3ULN (3 times the upper limit of normal). End-stage renal disease (ESRD) on dialysis, or estimated glomerular filtration rate (eGFR) <30 mL/min, or serum creatine >2.5 mg/dl [>221 umol/L]; Patients with serious physical diseases such as malignant tumors and autoimmune diseases. Severe cognitive or mental impairment. Pregnant and lactating women. Those who have contraindications or allergies to MRAs. Patients with hypoadrenocortical function. Participating in other clinical trials.
Sites / Locations
- Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mineralocorticoid Receptor Antagonists(MRAs)
Blank Control
Arm Description
Participants will treat with mineralocorticoid receptor antagonists(MRAs) (including spironolactone 20-60mg/ day, or eplerenone50-100mg/day, or finerenone 10-20mg/ day) in addition to the original antihypertensive drugs for 48 months.
Participants will be given the original antihypertensive drugs for 48 months.
Outcomes
Primary Outcome Measures
Occurrence of the composite endpoint
A composite endpoint comprised of occurrence of symptomatic stroke ( ischemic or hemorrhagic stroke), acute coronary syndrome (myocardial infarction and hospitalization for unstable angina), hospitalization for decompensated heart failure, coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]), atrial fibrillation, aortic dissection and dissection aneurysm, and death from cardiovascular causes.
Secondary Outcome Measures
Occurrence of symptomatic stroke ( ischemic or hemorrhagic)
Stroke is defined as a rapid onset of focal (or global) disturbance of cerebral function lasting more than 24 hours (except interrupted by surgery or death) without resolution of symptoms according to the World Health Organization. The diagnosis of stroke is confirmed by strict neurological examination, computed tomography (CT), or magnetic resonance imaging (MRI), and stroke subtypes are classified including ischemic or hemorrhagic, fatal or not fatal.
Occurrence of cardiac adverse events(Acute coronary syndrome and coronary revascularization)
Acute coronary syndrome includes myocardial infarction and hospitalization for unstable angina. The diagnosis of MI is based on the following criteria: (1) Patient has cardiac signs and symptoms, such as retrosternal pain last for at least 30 minutes, and not relieve to nitroglycerine during the attack; (2) Electrocardiographic abnormal findings of MI are observed; (3) Biochemical markers of cardiac damage are present.The diagnosis of unstable angina requires hospitalization for evaluation. The clinical presentation of unstable angina includes: (1) prolonged (>20 min) angina pain at rest; (2) new onset angina; (3) post-MI angina; (4) recent destabilization of previously stable angina with at least Canadian Cardiovascular Society Class III angina characteristics. Patients are treated with coronary revascularization by either PCI or CABG due to acute coronary syndromes (ACS) and stable ischemic heart disease (SIHD).
Occurrence of aortic dissection and dissection aneurysm
Aortic dissection and dissection aneurysms are diagnosed based on basic information, blood biochemical information and imaging information.
Occurrence of Hospitalization for acute decompensated heart failure
Diagnosis of acute decompensated heart failure requires a hospitalization or emergency department visit which provides an infusion therapy for clinical signs and symptoms consistent with cardiac decompensation or inadequate cardiac pump function, such as increasing or new onset shortness of breath, peripheral edema, paroxysmal dyspnea, orthopnea, or hypoxia.
Occurrence of Atrial fibrillation
Diagnosis of AF requires rhythm evidence of an ECG showing the typical pattern including absolutely irregular RR intervals and no discernible, distinct P waves.
Occurrence of all-cause death
All-cause death includes death due to any reasons during the trial. Evidence for death includes death certificates from hospitals or reports of home visit from investigators.
Occurrence of Decline in renal function or development of end stage renal disease (ESRD)
Decline in renal function is assessed by any of the following: (1) For patients with chronic kidney disease (eGFR <60 ml per minute per 1.73 m2) at baseline, the renal outcome was a composite of a decrease in the eGFR of 50% or more (confirmed by a subsequent laboratory test) or the development of ESRD requiring long-term dialysis or kidney transplantation; or (2) For participants without chronic kidney disease at baseline, the renal outcome was defined by a decrease in the eGFR of 30% or more to a value of less than 60 ml per minute per 1.73 m2.
First occurrence of diabetes mellitus
Diagnosis of incident diabetes mellitus includes the following criteria: (1) Fasting plasma glucose ≥ 126 mg/dl (≥ 7.0 mmol/dl); or (2) Oral glucose tolerance test 2-hour glucose in venous plasma ≥ 200 mg/dl (≥ 11.1 mmol/l); or (3) In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl (≥ 11.1 mmol/l); or (4) Glycosylated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol).
First occurrence of nonalcoholic fatty liver
Diagnosis of nonalcoholic fatty liver disease includes the following criteria: (1) imaging or histological evidence of hepatic steatosis; (2) Except other causes of secondary fat accumulation in the liver.
Occurrence of Decline in cognitive function
Decline in cognitive function includes sensory disturbance, memory disorders and thinking disorders, which is assessed by mini-mental state examination (MMSE).
Changes in vascular elasticity from baseline（ABI and baPWV）
Ankle brachial index [ABI],and brachial-ankle pulse wave velocity(baPWV) well-established non-invasive techniques for evaluating obstruction and stiffness of peripheral artery respectively, are considered for the purposes of cardiovascular risk assessment. ABI is the ratio of the average systolic blood pressure measured in brachial/ankle, and an ABI between and including 0.9 and 1.2 is considered normal, while a lesser than 0.9 indicates arterial disease. The unit measure of baPWV value is cm per second.
Changes in urine protein from baseline
Changes in cardiac structural indicators from baseline
Ventricular septal thickness and left ventricular posterior wall thickness were evaluated mainly by echocardiography.
Blood pressure control rate
Blood pressure control was assessed by home blood pressure or ambulatory blood pressure for 7 consecutive days
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05688579
Brief Title
Effect of MRA on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia
Acronym
EMRACHH
Official Title
Effect of Mineralcorticoid Recept Antagonist on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia：A Multicenter Randomized Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
April 16, 2023 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nanfang Li
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Elevated aldosterone causes moderate to severe increase in blood pressure, and leads to various target organ damage including cardiovascular ones. Aldosterone has been considered one of the important risk factors for cardiovascular and cerebrovascular diseases. Currently, the use of mineralocorticoid receptor antagonists(MRA) has been proven to reduce blood pressure levels, but long-term prognostic data are lacking in hypertensive patients. Therefore, the purpose of this clinical trial is to assess the effect of MRA on cardiovascular disease in patients with Hypertension and Hyperaldosteronemia.
Detailed Description
The trial will randomize about 7800 participants aged between 30 and 75 years with Hypertension and Hyperaldosteronemia(Plasma aldosterone concentration >12 ng/dl). All participants were randomly assigned to two different intervention groups. One group was treated with mineralocorticoid receptor antagonists(MRAs) (including spironolactone 20-60mg/ day, or eplerenone50-100mg/day, or finerenone 10-20mg/ day) in addition to the original antihypertensive drugs. One group was given the original antihypertensive drugs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Hyperaldosteronaemia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
8000 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mineralocorticoid Receptor Antagonists(MRAs)
Arm Type
Experimental
Arm Description
Participants will treat with mineralocorticoid receptor antagonists(MRAs) (including spironolactone 20-60mg/ day, or eplerenone50-100mg/day, or finerenone 10-20mg/ day) in addition to the original antihypertensive drugs for 48 months.
Arm Title
Blank Control
Arm Type
Placebo Comparator
Arm Description
Participants will be given the original antihypertensive drugs for 48 months.
Intervention Type
Drug
Intervention Name(s)
Mineralocorticoid Receptor Antagonists(MRAs)
Intervention Description
Participants will be treated with mineralocorticoid receptor antagonists(MRAs) in addition to the original antihypertensive drugs for 48 months.
Intervention Type
Other
Intervention Name(s)
Blank control
Other Intervention Name(s)
Placebo
Intervention Description
Participants will be treated with the original antihypertensive drugs for 48 months.
Primary Outcome Measure Information:
Title
Occurrence of the composite endpoint
Description
A composite endpoint comprised of occurrence of symptomatic stroke ( ischemic or hemorrhagic stroke), acute coronary syndrome (myocardial infarction and hospitalization for unstable angina), hospitalization for decompensated heart failure, coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]), atrial fibrillation, aortic dissection and dissection aneurysm, and death from cardiovascular causes.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Occurrence of symptomatic stroke ( ischemic or hemorrhagic)
Description
Stroke is defined as a rapid onset of focal (or global) disturbance of cerebral function lasting more than 24 hours (except interrupted by surgery or death) without resolution of symptoms according to the World Health Organization. The diagnosis of stroke is confirmed by strict neurological examination, computed tomography (CT), or magnetic resonance imaging (MRI), and stroke subtypes are classified including ischemic or hemorrhagic, fatal or not fatal.
Time Frame
4 years
Title
Occurrence of cardiac adverse events(Acute coronary syndrome and coronary revascularization)
Description
Acute coronary syndrome includes myocardial infarction and hospitalization for unstable angina. The diagnosis of MI is based on the following criteria: (1) Patient has cardiac signs and symptoms, such as retrosternal pain last for at least 30 minutes, and not relieve to nitroglycerine during the attack; (2) Electrocardiographic abnormal findings of MI are observed; (3) Biochemical markers of cardiac damage are present.The diagnosis of unstable angina requires hospitalization for evaluation. The clinical presentation of unstable angina includes: (1) prolonged (>20 min) angina pain at rest; (2) new onset angina; (3) post-MI angina; (4) recent destabilization of previously stable angina with at least Canadian Cardiovascular Society Class III angina characteristics. Patients are treated with coronary revascularization by either PCI or CABG due to acute coronary syndromes (ACS) and stable ischemic heart disease (SIHD).
Time Frame
4 years
Title
Occurrence of aortic dissection and dissection aneurysm
Description
Aortic dissection and dissection aneurysms are diagnosed based on basic information, blood biochemical information and imaging information.
Time Frame
4 years
Title
Occurrence of Hospitalization for acute decompensated heart failure
Description
Diagnosis of acute decompensated heart failure requires a hospitalization or emergency department visit which provides an infusion therapy for clinical signs and symptoms consistent with cardiac decompensation or inadequate cardiac pump function, such as increasing or new onset shortness of breath, peripheral edema, paroxysmal dyspnea, orthopnea, or hypoxia.
Time Frame
4 years
Title
Occurrence of Atrial fibrillation
Description
Diagnosis of AF requires rhythm evidence of an ECG showing the typical pattern including absolutely irregular RR intervals and no discernible, distinct P waves.
Time Frame
4 years
Title
Occurrence of all-cause death
Description
All-cause death includes death due to any reasons during the trial. Evidence for death includes death certificates from hospitals or reports of home visit from investigators.
Time Frame
4 years
Title
Occurrence of Decline in renal function or development of end stage renal disease (ESRD)
Description
Decline in renal function is assessed by any of the following: (1) For patients with chronic kidney disease (eGFR <60 ml per minute per 1.73 m2) at baseline, the renal outcome was a composite of a decrease in the eGFR of 50% or more (confirmed by a subsequent laboratory test) or the development of ESRD requiring long-term dialysis or kidney transplantation; or (2) For participants without chronic kidney disease at baseline, the renal outcome was defined by a decrease in the eGFR of 30% or more to a value of less than 60 ml per minute per 1.73 m2.
Time Frame
4 years
Title
First occurrence of diabetes mellitus
Description
Diagnosis of incident diabetes mellitus includes the following criteria: (1) Fasting plasma glucose ≥ 126 mg/dl (≥ 7.0 mmol/dl); or (2) Oral glucose tolerance test 2-hour glucose in venous plasma ≥ 200 mg/dl (≥ 11.1 mmol/l); or (3) In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl (≥ 11.1 mmol/l); or (4) Glycosylated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol).
Time Frame
4 years
Title
First occurrence of nonalcoholic fatty liver
Description
Diagnosis of nonalcoholic fatty liver disease includes the following criteria: (1) imaging or histological evidence of hepatic steatosis; (2) Except other causes of secondary fat accumulation in the liver.
Time Frame
4 years
Title
Occurrence of Decline in cognitive function
Description
Decline in cognitive function includes sensory disturbance, memory disorders and thinking disorders, which is assessed by mini-mental state examination (MMSE).
Time Frame
4 years
Title
Changes in vascular elasticity from baseline（ABI and baPWV）
Description
Ankle brachial index [ABI],and brachial-ankle pulse wave velocity(baPWV) well-established non-invasive techniques for evaluating obstruction and stiffness of peripheral artery respectively, are considered for the purposes of cardiovascular risk assessment. ABI is the ratio of the average systolic blood pressure measured in brachial/ankle, and an ABI between and including 0.9 and 1.2 is considered normal, while a lesser than 0.9 indicates arterial disease. The unit measure of baPWV value is cm per second.
Time Frame
1-4 years
Title
Changes in urine protein from baseline
Time Frame
1-4 years
Title
Changes in cardiac structural indicators from baseline
Description
Ventricular septal thickness and left ventricular posterior wall thickness were evaluated mainly by echocardiography.
Time Frame
1-4 years
Title
Blood pressure control rate
Description
Blood pressure control was assessed by home blood pressure or ambulatory blood pressure for 7 consecutive days
Time Frame
1-3months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: 18-75 years old;
Blood pressure ≥140/90 mmHg, or have taken antihypertensive drugs;
Plasma aldosterone concentration> 12ng/ dL;
Serum potassium < 4.8mmol/L;
Signed the written informed consent.
Exclusion Criteria:
SBP/DBP≥190/120mmHg, DBP<60 mmHg;
Known secondary cause of hypertension, including pheochromocytoma, primary aldosteronism (adrenal tumor > 1cm), Cushing's syndrome, renal artery stenosis, renin tumor, connotation of aorta, etc.;
History of ischemic or hemorrhagic stroke within the last 3 months (not lacunar infarction and transient ischemic attack [TIA]).
History of Hospitalization for myocardial infarction or unstable angina, or coronary revascularization (PCI or CABG) within the last 3 months.
History of aortic dissection/dissection aneurysm rupture.
History of NYHA Grade III-IV heart failure or hospitalization Aggravated chronic heart failure upon admission within the last 3 months.
A history of persistent atrial fibrillation, atrial flutter, or other severe arrhythmias on admission (including sinus delay, diseased sinus, high atrioventricular block, frequent ventricular morning, etc.).
Severe liver disease or liver dysfunction: AST, ALT, or ALP > 5ULN (5 times the upper limit of normal), or BIL > 3ULN (3 times the upper limit of normal).
End-stage renal disease (ESRD) on dialysis, or estimated glomerular filtration rate (eGFR) <30 mL/min, or serum creatine >2.5 mg/dl [>221 umol/L];
Patients with serious physical diseases such as malignant tumors and autoimmune diseases.
Severe cognitive or mental impairment.
Pregnant and lactating women.
Those who have contraindications or allergies to MRAs.
Patients with hypoadrenocortical function.
Participating in other clinical trials.
Facility Information:
Facility Name
Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region
City
Urumqi
State/Province
Xinjiang
ZIP/Postal Code
830001
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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21536989
Citation
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Results Reference
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29129575
Citation
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Citation
Cannone V, Buglioni A, Sangaralingham SJ, Scott C, Bailey KR, Rodeheffer R, Redfield MM, Sarzani R, Burnett JC Jr. Aldosterone, Hypertension, and Antihypertensive Therapy: Insights From a General Population. Mayo Clin Proc. 2018 Aug;93(8):980-990. doi: 10.1016/j.mayocp.2018.05.027.
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Citation
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Citation
Inoue K, Goldwater D, Allison M, Seeman T, Kestenbaum BR, Watson KE. Serum Aldosterone Concentration, Blood Pressure, and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis. Hypertension. 2020 Jul;76(1):113-120. doi: 10.1161/HYPERTENSIONAHA.120.15006. Epub 2020 May 18. Erratum In: Hypertension. 2021 Mar 3;77(3):e34.
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Effect of MRA on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia
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