Effect of MRA on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia

Hypertension Clinical Trial

— EMRACHH  

Official title:

Effect of Mineralcorticoid Recept Antagonist on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia：A Multicenter Randomized Controlled Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05688579
• Other study ID #: A.HT.2022.8.4
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: April 16, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2023
• Source: People's Hospital of Xinjiang Uygur Autonomous Region
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 8000
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age: 18-75 years old;

2. Blood pressure =140/90 mmHg, or have taken antihypertensive drugs;

3. Plasma aldosterone concentration> 12ng/ dL;

4. Serum potassium < 4.8mmol/L;

5. Signed the written informed consent.

Exclusion Criteria:

1. SBP/DBP=190/120mmHg, DBP<60 mmHg;

2. Known secondary cause of hypertension, including pheochromocytoma, primary aldosteronism (adrenal tumor > 1cm), Cushing's syndrome, renal artery stenosis, renin tumor, connotation of aorta, etc.;

3. History of ischemic or hemorrhagic stroke within the last 3 months (not lacunar infarction and transient ischemic attack [TIA]).

4. History of Hospitalization for myocardial infarction or unstable angina, or coronary revascularization (PCI or CABG) within the last 3 months.

5. History of aortic dissection/dissection aneurysm rupture.

6. History of NYHA Grade III-IV heart failure or hospitalization Aggravated chronic heart failure upon admission within the last 3 months.

7. 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.).

8. 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).

9. 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];

10. Patients with serious physical diseases such as malignant tumors and autoimmune diseases.

11. Severe cognitive or mental impairment.

12. Pregnant and lactating women.

13. Those who have contraindications or allergies to MRAs.

14. Patients with hypoadrenocortical function.

15. Participating in other clinical trials.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Hyperaldosteronism
• Hypertension

Intervention

Drug:
• Mineralocorticoid Receptor Antagonists(MRAs)
Participants will be treated with mineralocorticoid receptor antagonists(MRAs) in addition to the original antihypertensive drugs for 48 months.

Other:
• Blank control
Participants will be treated with the original antihypertensive drugs for 48 months.

Locations

Country	Name	City	State
China	Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region	Urumqi	Xinjiang

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Li

Country where clinical trial is conducted

China, 

References & Publications (7)

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 — View 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/HYPERTENSIONAH — View Citation

Joseph JJ, Echouffo-Tcheugui JB, Kalyani RR, Yeh HC, Bertoni AG, Effoe VS, Casanova R, Sims M, Wu WC, Wand GS, Correa A, Golden SH. Aldosterone, Renin, Cardiovascular Events, and All-Cause Mortality Among African Americans: The Jackson Heart Study. JACC H — View Citation

Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol — View Citation

Ni X, Zhang J, Zhang P, Wu F, Xia M, Ying G, Chen J. Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study. J Clin Hypertens (Greenwich). 2014 Sep;16(9):658-63. doi: 10.1111/jch.12374. Epub 2014 Jul 22. — View Citation

Vaclavik J, Sedlak R, Plachy M, Navratil K, Plasek J, Jarkovsky J, Vaclavik T, Husar R, Kocianova E, Taborsky M. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension. 2011 Jun;57(6):1069-75. doi: 10.1161/HYPERTENSIONAHA.111.169961. Epub 2011 May 2. Erratum In: Hypertension. 2015 Feb;65(2):e7. — View Citation

Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, Ford I, Cruickshank JK, Caulfield MJ, Salsbury J, Mackenzie I, Padmanabhan S, Brown MJ; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	4 years
Secondary	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.	4 years
Secondary	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).	4 years
Secondary	Occurrence of aortic dissection and dissection aneurysm	Aortic dissection and dissection aneurysms are diagnosed based on basic information, blood biochemical information and imaging information.	4 years
Secondary	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.	4 years
Secondary	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.	4 years
Secondary	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.	4 years
Secondary	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.	4 years
Secondary	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).	4 years
Secondary	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.	4 years
Secondary	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).	4 years
Secondary	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.	1-4 years
Secondary	Changes in urine protein from baseline		1-4 years
Secondary	Changes in cardiac structural indicators from baseline	Ventricular septal thickness and left ventricular posterior wall thickness were evaluated mainly by echocardiography.	1-4 years
Secondary	Blood pressure control rate	Blood pressure control was assessed by home blood pressure or ambulatory blood pressure for 7 consecutive days	1-3months