Early Aldo Blockade in Subclinical PA

This trial aims to evaluate the preventive effect of early intervention with eplerenone, a highly selective nonsteroidal mineralocorticoid receptor antagonist, against new-onset hypertension in normotensive patients with subclinical primary aldosteronism (PA), as well as its cardiorenal target organ protective effects and long-term safety profile. The trial will be conducted across 15 to 20 tertiary hospitals nationwide with established expertise in PA diagnosis and management. A total of 880 eligible patients aged 30 to 55 years with normal blood pressure and biochemically/functionally confirmed subclinical PA will be enrolled and randomly assigned to the eplerenone group or the placebo group at a 1:1 ratio. The eplerenone group will receive a dose titration regimen with a target maintenance dose of 50 mg once daily orally, while the placebo group will follow a matched sham titration protocol. The double-blind treatment period will last 3 years, with an extension to 5 years permitted based on interim analysis findings. The primary endpoint is the incidence of new-onset hypertension within 3 years, adjudicated blindly by an independent Clinical Endpoint Committee (CEC). Secondary endpoints include alterations in biomarkers of cardiorenal target organ damage, improvements in endocrine parameters, changes in adrenal nodule volume, and patient-reported outcomes. Safety endpoints cover the incidence of adverse events such as hyperkalemia, acute kidney injury, and hypotension. This trial will fill a critical gap in evidence-based medicine regarding early intervention for subclinical PA for the first time. Its findings are expected to revise international clinical practice guidelines for PA and deliver a novel precision intervention strategy for the primary prevention of hypertension.