Clinical trial NCT05688579: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Hypertension
Hyperaldosteronaemia
Lead sponsor: People's Hospital of Xinjiang Uygur Autonomous Region
Sponsor class: OTHER
First posted: 2023-01-18
Enrollment: 8000
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of the composite endpoint
timeFrame: 4 years
Secondary outcomes:
measure: Occurrence of symptomatic stroke ( ischemic or hemorrhagic)
timeFrame: 4 years
measure: Occurrence of cardiac adverse events(Acute coronary syndrome and coronary revascularization)
timeFrame: 4 years
measure: Occurrence of aortic dissection and dissection aneurysm
timeFrame: 4 years
measure: Occurrence of Hospitalization for acute decompensated heart failure
timeFrame: 4 years
measure: Occurrence of Atrial fibrillation
timeFrame: 4 years
measure: Occurrence of all-cause death
timeFrame: 4 years
measure: Occurrence of Decline in renal function or development of end stage renal disease (ESRD)
timeFrame: 4 years
measure: First occurrence of diabetes mellitus
timeFrame: 4 years
measure: First occurrence of nonalcoholic fatty liver
timeFrame: 4 years
measure: Occurrence of Decline in cognitive function
timeFrame: 4 years
measure: Changes in vascular elasticity from baseline（ABI and baPWV）
timeFrame: 1-4 years
measure: Changes in urine protein from baseline
timeFrame: 1-4 years
measure: Changes in cardiac structural indicators from baseline
timeFrame: 1-4 years
measure: Blood pressure control rate
timeFrame: 1-3months
Other outcomes:
Locations:
city: Urumqi
country: China
facility: Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang
Study officials:
References:
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.
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. 2018 Jan;6(1):41-50. doi: 10.1016/S2213-8587(17)30319-4. Epub 2017 Nov 9.
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 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.
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.
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 Heart Fail. 2017 Sep;5(9):642-651. doi: 10.1016/j.jchf.2017.05.012. Epub 2017 Aug 16.
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.
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.