Clinical trial NCT06381323: The Clinical Efficacy and Safety of Finerenone in the Treatment of Primary Aldosteronism
Official title: Study on the Clinical Efficacy and Safety of the New Mineralocorticoid Receptor Antagonist Finerenone in the Treatment of Primary Aldosteronism: a Multicenter, Prospective, Open-label Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Primary Aldosteronism
Finerenone
Mineralocorticoid Receptor Antagonist
Keywords: Primary Aldosteronism
Finerenone
Mineralocorticoid Receptor Antagonist
Hypertension
24-hour ambulatory blood pressure monitoring
Daytime SBP
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2024-04-24
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of our research is to clarify the therapeutic efficacy and safety of Finerenone in patients with Primary Aldosteronism and explore the effective clinical predictive indicators of Finerenone in the treatment of Primary Aldosteronism.

Detailed description: Primary aldosteronism(PA) is a clinical syndrome characterized by autonomous aldosterone secretion in the body caused by adrenal cortical adenoma or hyperplasia not regulated by renin, angiotensin II, and sodium status regulation. It is the most common cause of secondary hypertension, accounting for about 10% of all hypertensive patients. The latest prospective study in China showed that the prevalence of primary aldosteronism in newly diagnosed hypertensive patients was 4%, with an additional 3% of suspicious primary aldosteronism patients. Excessive activation of the mineralocorticoid receptor (MR) in the body leads to well-known increased circulating volume overload, hypertension, and hypokalemia, as well as significantly increased cardiovascular, renal, and mortality risks. Therefore, primary aldosteronism is currently considered a new public health problem and has important implications for early diagnosis and precise treatment of primary aldosteronism.

Only about 30% of patients with PA (aldosterone-producing adenoma or unilateral adrenal hyperplasia) can be cured or relieved through surgical resection, while about 65% of patients with primary aldosteronism caused by bilateral adrenal cortical hyperplasia require drug treatment. Currently, the only available drug in China is the first-generation mineralocorticoid receptor antagonist, spironolactone, which is greatly limited in its use due to its significant side effects on the gonads caused by the blockade of androgens and progesterones. Another MRA, eplerenone, which has not yet been marketed in China, is expensive and clinically inferior to spironolactone. Therefore, a large number of patients with primary aldosteronism are currently not using or using low doses of spironolactone, unable to fully counteract the high aldosterone effect, and unable to effectively control the risk of cardiovascular and renal damage. Therefore, it is necessary to explore new drugs for the treatment of primary aldosteronism.

Finerenone is a newly developed novel non-steroidal MRA, which has higher affinity and selectivity for MR binding compared to steroidal MRA (spironolactone or eplerenone). Existing clinical research results suggest that Finerenone can effectively reduce the risk of cardiovascular and renal damage in patients with chronic kidney disease and diabetes, and has good safety.

This study aims to be the first internationally to conduct clinical research on the use of the novel mineralocorticoid receptor antagonist finerenone for the treatment of primary aldosteronism. Through a multicenter, prospective, open-label study, the clinical efficacy and safety of this medication will be clearly established, providing high-level evidence of the use of finerenone in patients with primary aldosteronism. The project's results will offer a new option for the pharmacological treatment of primary aldosteronism, with the goal of better controlling patients' biochemical abnormalities, effectively reducing the risk of cardiovascular and renal damage, and improving disease prognosis.

Eligibility criteria: Inclusion Criteria:

1. Age:18-75 years old.
2. History of hypertension, with a sitting SBP ≥140 and \<180 mmHg, and a sitting DBP ≥90 and \<120 mmHg during the last two evaluations within the observation period.
3. Patients with PA who are eligible for drug treatment.
4. Diagnostic criteria for primary aldosteronism: (1) Hypertension or use of antihypertensive medications, with or without hypokalemia; (2) Screening test: Baseline plasma aldosterone to renin ratio (ARR) \>30 (ng/dl)/(ng/ml/h) or ARR \>2.4 (ng/dl)/(mU/L), with plasma aldosterone \>15 ng/dl and plasma renin activity \<1.0 ng/ml/h; (3) At least one confirmed test is positive: ① After a captopril test, plasma aldosterone decreases by \<30% or plasma aldosterone is ≥11 ng/dl, with suppressed renin activity; ② Sitting saline infusion test results in a plasma aldosterone ≥10 ng/dl.
5. eGFR ≥60 ml/ (min\*1.73m2).
6. Signed informed consent form.

Exclusion Criteria:

1. Other secondary hypertension (such as renal vascular hypertension, Cushing's syndrome, subclinical Cushing's syndrome, and pheochromocytoma) or hypertensive crisis.
2. Orthostatic hypotension.
3. Heart failure, acute myocardial infarction, stroke, transient ischemic attack, or other acute cardiovascular events within the past 6 months.
4. History of adrenal surgery within the past 6 months.
5. History of carotid artery surgery within the past 6 months.
6. History of arterial vascular reconstruction surgery within the past 6 months.
7. Hospitalization within the past year due to severe hyperkalemia, with serum potassium levels \<2.5 or ≥5.0 mmol/L.
8. Abnormal liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5× upper limit of normal (ULN), total bilirubin (TBIL) \> 1.5× ULN.
9. Use of spironolactone, hydralazine, or minoxidil within 30 days prior to enrollment.
10. Concurrent use of potent CYP3A4 inhibitors or inducers for treatment.
11. Known or suspected tumors; other autoimmune diseases, uncontrolled infectious diseases, severe respiratory, blood, and neurological diseases.
12. Pregnancy or planning pregnancy within 3 months before or after treatment, and breastfeeding women.
13. Mental illness, alcohol or drug abuse, inability to cooperate with treatment.
14. Patients with pacemakers.
15. Participation in other clinical trials.

Primary outcomes:
measure: 24h systolic BP drop value
timeFrame: 12 weeks
Secondary outcomes:
measure: The change of diastolic BP from the baseline level after Finerenone treatment
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
measure: Hypertension remission rate
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
measure: Change of serum potassium level
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
measure: Change of plasma renin activity
timeFrame: Baseline,4 week,8 weeks,12 weeks,16 weeks
measure: Change of ARR
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
measure: Change of UACR
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
measure: Change of eGFR
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Other outcomes:
measure: Incidence of Treatment-Adverse Events as assessed by gynaecomastia, mastodynia, menstrual abnormalities, impotence, hyperkalemia and other adverse events.
timeFrame: Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Locations:
city: Nanjing
country: China
facility: Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Ping Li
role: STUDY_DIRECTOR
References: