Primary Aldosteronism
Conditions
Keywords
treatment, intensive blood pressure control
Brief summary
The goal of this clinical trial is to evaluate whether an intensive blood pressure control strategy (systolic blood pressure target \<120 mmHg) is more effective than a standard strategy (systolic blood pressure target \<140 mmHg) in reducing the risk of cardiovascular events in patients with primary aldosteronism. The main question it aims to answer is: Does the intensive blood pressure control strategy reduce the risk of composite cardiovascular events more than the standard strategy in patients with primary aldosteronism? The study employs a randomized design, allocating participants in a 1:1 ratio to either the Intensive Treatment Group or the Standard Treatment Group. Researchers will compare the differences in cardiovascular outcomes and safety profiles between the two groups over a planned follow-up period of 6 to 10 years. Participants will: Undergo randomization and adhere to the assigned blood pressure management protocol. Attend regular follow-up visits for blood pressure measurement, laboratory tests, questionnaires, etc. Report any adverse events or changes in health status.
Interventions
Adjusting antihypertensive medications keeps the patient's systolic blood pressure controlled at below 120 mmHg.
Adjusting antihypertensive medications keeps the patient's systolic blood pressure controlled between 120 and 140 mmHg.
Sponsors
Chongqing Medical University
First Affiliated Hospital of Chongqing Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to either an intensive treatment group or a standard treatment group.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria to be eligible for enrollment: 1. A diagnosis of PA meeting the following criteria: an upright plasma aldosterone-to-renin ratio (ARR) ≥20 (pg/mL)/(μIU/mL) or ≥300 (pg/mL)/(ng/mL/h); and at least one positive confirmatory test: plasma aldosterone ≥110 pg/mL after the captopril challenge test (CCT) or plasma aldosterone ≥80 pg/mL after the seated saline infusion test (SSIT). Note: For patients with an upright ARR ratio between 10-20 (pg/mL)/(μIU/mL), the screening result can also be considered positive if they have additional high-risk factors such as adrenal lesions or resistant hypertension. Patients receiving medications that may suppress renin and lead to false-positive results (e.g., β-adrenergic blockers and centrally acting α₂-agonists such as clonidine or α-methyldopa) should discontinue these medications and repeat testing after a 2-week washout period. 2. Systolic blood pressure of 140-190 mmHg (or currently receiving antihypertensive treatment). Notes: (1) Office mean seated blood pressure is defined as the average of three seated blood pressure measurements obtained at any single on-site visit. (2) There is no diastolic blood pressure criterion for inclusion. 3. Increased risk of cardiovascular disease (one or more of the following): * Previous history of clinical CVD (≥ 3 months) * Stroke * Myocardial infarction * Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) * Carotid endarterectomy or carotid stenting * Peripheral artery disease (PAD) with revascularization * Acute coronary syndrome with or without resting ECG change, ECG changes on a graded exercise test, or positive cardiac imaging study * Subclinical CVD within 3 years * ≥50% stenosis of a coronary, carotid, or lower extremity artery * Ankle brachial index (ABI) ≤0.90 * Chest pain with evidence of myocardial ischemia * 2 or more CVD risk factors * Male ≥50 years or female ≥55 years * History of smoking (≥1 cigarette per day in the past 12 months) * Diabetes mellitus * BMI \>28 kg/m² * Dyslipidemia despite receiving maximally tolerated statin therapy: LDL cholesterol \>130 mg/dL (\>3.36 mmol/L), or HDL cholesterol \<40 mg/dL (\<1.03 mmol/L) in males or \<50 mg/dL (\<1.29 mmol/L) in females * Family history of premature coronary heart disease (defined as myocardial infarction or coronary revascularization) in a first-degree relative: male relative \<55 years or female relative \<65 years * Microalbuminuria (Note: If microalbuminuria is the only criterion, a repeat test is required for confirmation) * Estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m²
Exclusion criteria
1. Patients with PA who are planned to undergo adrenal surgical treatment. 2. Other clearly diagnosed forms of secondary hypertension (excluding subclinical Cushing's syndrome and obstructive sleep apnea \[OSA\]). 3. Severe hypertension: systolic blood pressure (SBP) ≥190 mmHg or diastolic blood pressure (DBP) ≥110 mmHg. 4. Diastolic blood pressure \<60 mmHg (without antihypertensive medication). 5. Myocardial infarction, unstable angina, stroke, or coronary revascularization (PCI or CABG) within the past 3 months. 6. Planned coronary revascularization (PCI or CABG) within the next 6 months. 7. Severe valvular heart disease, or valvular disease likely to require surgical or percutaneous valve replacement during the study period. 8. Hypertrophic cardiomyopathy (HCM). Definition: A disease characterized by unexplained left ventricular hypertrophy, with a non-dilated ventricular cavity and absence of other cardiac or systemic diseases. Clinically, HCM is usually diagnosed by echocardiography, defined as a maximum left ventricular wall thickness ≥15 mm, or 13-14 mm (considered borderline), particularly in the presence of additional supporting evidence (e.g., a family history of HCM). In elderly patients with left ventricular hypertrophy and a long-standing history of systemic hypertension, a diagnosis of HCM may be established if a definite sarcomeric gene mutation is identified, or if left ventricular wall thickness is markedly \>25 mm and/or there is left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve and mitral valve-septal contact. 9. NYHA functional class III-IV heart failure or left ventricular ejection fraction \<35%. 10. ALT or AST \>2.5 times the upper limit of normal, or active liver disease. 11. Dialysis dependence or eGFR \<30 mL/min/1.73 m². 12. Polycystic kidney disease or glomerulonephritis. 13. Any condition with an expected life expectancy \<5 years. 14. Factors likely to affect adherence to the intervention, including: * Alcohol abuse or drug abuse within the past 12 months. * History of severe non-adherence to medication or follow-up. * Residence far from the study center or planned relocation within 5 years. * Clinical diagnosis or treatment of dementia, or cognitive impairment preventing adherence to the protocol. * Other medical, psychiatric, or behavioral factors that may interfere with study participation. 15. Failure to provide written informed consent. 16. Current participation in another interventional study. 17. Pregnancy, planned pregnancy, or women of childbearing potential not using effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome: The number of composite cardiovascular events that occurred | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | A composite of major cardiovascular events, including nonfatal myocardial infarction, unstable angina, nonfatal stroke, hospitalization or treatment for heart failure, atrial fibrillation, coronary or non-coronary revascularization, and cardiovascular death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Myocardial Infarction (Fatal and Non-fatal) | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631events are reached (anticipated follow-up: 6-10 years). | — |
| Total Stroke (Fatal and Non-fatal) | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631events are reached (anticipated follow-up: 6-10 years). | — |
| Ischemic Stroke | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| Hemorrhagic Stroke | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| Heart Failure Requiring Hospitalization/Treatment or Death from Heart Failure | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated median follow-up: 6-10 years). | — |
| Atrial fibrillation | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| Revascularization (Including Coronary and Non-Coronary) | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| cardiovascular death | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| All-Cause Death | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| Health-Related Quality of Life | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years) | Patient-reported quality of life measured via the validated SF-36 questionnaire. The overall summary score ranges from 0 (worst imaginable health) to 100 (perfect health); higher scores reflect superior health-related quality of life. Assessed at scheduled follow-up visits throughout study follow-up. |
| Number of participants with adjudicated renal composite events (CKD progression, new-onset CKD, new-onset albuminuria) assessed via serial serum creatinine and urine ACR laboratory testing | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | CKD progression: defined as a decline in eGFR of ≥50%, progression to end-stage kidney disease (requiring dialysis or kidney transplantation), or eGFR \<15 ml/min/1.73 m², confirmed by two laboratory measurements. New-onset CKD: defined as a decline in eGFR of \>30% with eGFR \<60 ml/min/1.73 m², requiring confirmation. New-onset proteinuria: defined as an increase in urine albumin-to-creatinine ratio (ACR) from \<30 mg/g to \>30 mg/g, requiring confirmation. |
| Major Coronary Artery Disease (Non-fatal myocardial infarction, Unstable angina, Coronary revascularization, Death from coronary heart disease) | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
| Expanded Outcome (Primary Outcome + All-Cause Death) | Time from randomization to first occurrence of any component of the composite cardiovascular endpoint, assessed throughout the study until 631 events are reached (anticipated follow-up: 6-10 years). | — |
Countries
China
Contacts
CONTACTQifu Li, phD
Outcome results
None listed