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

NCT05688579 | Enrolling By Invitation Phase 4

• 1 other identifier: A.HT.2022.8.4
• Study Type: interventional
• Target: 8,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; Hyperaldosteronaemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Occurrence of symptomatic stroke ( ischemic or hemorrhagic)

  4 years

• Occurrence of cardiac adverse events(Acute coronary syndrome and coronary revascularization)

  4 years

• Occurrence of aortic dissection and dissection aneurysm

  4 years

• Occurrence of Hospitalization for acute decompensated heart failure

  4 years

• Occurrence of Atrial fibrillation

  4 years

Study Arms (2)

Mineralocorticoid Receptor Antagonists(MRAs)

EXPERIMENTAL

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.

Drug: Mineralocorticoid Receptor Antagonists(MRAs)

Blank Control

PLACEBO COMPARATOR

Participants will be given the original antihypertensive drugs for 48 months.

Other: Blank control

Interventions

Mineralocorticoid Receptor Antagonists(MRAs) DRUG

Participants will be treated with mineralocorticoid receptor antagonists(MRAs) in addition to the original antihypertensive drugs for 48 months.

Mineralocorticoid Receptor Antagonists(MRAs)

Blank control OTHER

Participants will be treated with the original antihypertensive drugs for 48 months.

Also known as: Placebo

Blank Control

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nanfang Li: lead

Study Sites (1)

Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region

Ürümqi, Xinjiang, 830001, China

Location

Related Publications (7)

• 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.

  PMID: 21536989 BACKGROUND

• 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. 2018 Jan;6(1):41-50. doi: 10.1016/S2213-8587(17)30319-4. Epub 2017 Nov 9.

  PMID: 29129575 RESULT

• 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 doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015 Nov 21;386(10008):2059-2068. doi: 10.1016/S0140-6736(15)00257-3. Epub 2015 Sep 20.

  PMID: 26414968 RESULT

• 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.

  PMID: 30077215 RESULT

• 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 Heart Fail. 2017 Sep;5(9):642-651. doi: 10.1016/j.jchf.2017.05.012. Epub 2017 Aug 16.

  PMID: 28822744 RESULT

• 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.

  PMID: 32418495 RESULT

• 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.

  PMID: 25052724 RESULT

MeSH Terms

Conditions

Hypertension; Hyperaldosteronism

Interventions

Mineralocorticoid Receptor Antagonists

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Chief physician

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: January 18, 2023
• Study Start: April 16, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)