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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Occurrence of the composite endpoint [Срок оценки: 4 years]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

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

Публикации

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• 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
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• 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

Идентификаторы

NCT: NCT05688579 · A.HT.2022.8.4

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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