The Clinical Efficacy and Safety of Finerenone in the Treatment of Primary Aldosteronism

Primary Aldosteronism Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06381323
• Other study ID #: PA2024
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2024
• Est. completion date: April 1, 2027

Study information

• Verified date: March 2024
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Ping Li, Ph.D
• Phone: 86-025-83106666
• Email: li78321[@]yeah.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: April 1, 2027
• Est. primary completion date: March 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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: ? After a captopril test, plasma aldosterone decreases by <30% or plasma aldosterone is =11 ng/dl, with suppressed renin activity; ? 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.

Related Conditions & MeSH terms

• Hyperaldosteronism
• Mineralocorticoid Receptor Antagonist
• Primary Aldosteronism

Intervention

Drug:
• Finerenone
All eligible subjects enter a 2-week enrollment phase and only take stable doses of controlled-release nifedipine. After completing baseline examinations, subjects with SBP <180 and =140 mmHg and DBP <120 and =90 mmHg enter the follow-up phase of the treatment period. Eligible subjects receive a starting dose of 20 mg qd of Finerenone. If the blood pressure is still =140/90 mmHg at week 4, serum potassium is <5.0 mmol/L, and eGFR has decreased <30% compared to baseline, the Finerenone dose is adjusted to 40 mg qd.

Locations

Country	Name	City	State
China	Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Treatment-Adverse Events as assessed by gynaecomastia, mastodynia, menstrual abnormalities, impotence, hyperkalemia and other adverse events.	Adverse effects such as gynaecomastia, mastodynia, menstrual abnormalities and impotence due to its agonist activity.; Hyperkalemia.; Other adverse events.	Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Primary	24h systolic BP drop value	The average daytime systolic blood pressure drop from baseline levels after treatment with Finerenone at 12 weeks.	12 weeks
Secondary	The change of diastolic BP from the baseline level after Finerenone treatment	To Clarify the antihypertensive effect of Finerenone by measuring daytime diastolic blood pressure from baseline to the end of treatment .	Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Secondary	Hypertension remission rate	The proportion of patients with SBP<140mmHg and DBP<90mmHg.	Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Secondary	Change of serum potassium level	Proportion of patients with normal blood potassium levels (serum potassium level = 3.5mmol/L and = 5.5mmol/L).	Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Secondary	Change of plasma renin activity	to compare plasma renin activity during the progression	Baseline,4 week,8 weeks,12 weeks,16 weeks
Secondary	Change of ARR	To see if Finerenone can influence ARR[(ng/dl)/(ng/ml/h)]	Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Secondary	Change of UACR	Compared to the placebo group, the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease decreased by 18% after treatment with nonnarcotic ketones.	Baseline,4 weeks,8 weeks,12 weeks,16 weeks
Secondary	Change of eGFR	Estimated glomerular filtration rate (eGFR) decline condition.	Baseline,4 weeks,8 weeks,12 weeks,16 weeks