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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Occurrence of the composite endpoint [Time frame: 4 years]

Secondary outcome measures (12)

• Occurrence of symptomatic stroke ( ischemic or hemorrhagic) [Time frame: 4 years]
• Occurrence of cardiac adverse events(Acute coronary syndrome and coronary revascularization) [Time frame: 4 years]
• Occurrence of aortic dissection and dissection aneurysm [Time frame: 4 years]
• Occurrence of Hospitalization for acute decompensated heart failure [Time frame: 4 years]
• Occurrence of Atrial fibrillation [Time frame: 4 years]
• Occurrence of all-cause death [Time frame: 4 years]
• Occurrence of Decline in renal function or development of end stage renal disease (ESRD) [Time frame: 4 years]
• First occurrence of diabetes mellitus [Time frame: 4 years]
• First occurrence of nonalcoholic fatty liver [Time frame: 4 years]
• Occurrence of Decline in cognitive function [Time frame: 4 years]
• Changes in vascular elasticity from baseline（ABI and baPWV） [Time frame: 1-4 years]
• Changes in urine protein from baseline [Time frame: 1-4 years]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

China · 1 center

• Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region — Ürümqi

Publications

• 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
• 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
• 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. 201 PMID 26414968
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT05688579 · A.HT.2022.8.4

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗