Comparing the Efficacy and Safety of Finerenone and Spironolactone in the Treatment of Primary Aldosteronism

Compare the Efficacy and Safety of Finerenone, a New Type of Mineralocorticoid Receptor Antagonist, and Spironolactone in the Treatment of Primary Aldosteronism: a Single-Center, Prospective, Randomized Controlled Study

Primary aldosteronism (PA) is thought to be the most common secondary endocrine form of hypertension. Compared with patients with essential hypertension with similar blood pressure, patients with PA have significantly higher atrial fibrillation, myocardial infarction, heart failure, stroke, deterioration of renal function and all-cause mortality. Therefore, early and systematic implementation of effective surgical or medical treatment is essential to prevent or reverse the excess vascular events and mortality of these patients. The patients with bilateral PA were mainly treated with mineralocorticoid receptor antagonists (MRAs). The MRA spironolactone is effective at lowering BP and reversing the harmful metabolic consequences, but its use is limited by adverse effects such as gynaecomastia, mastodynia, menstrual abnormalities and impotence due to its agonist activity at the progesterone receptor and antagonist activity at the androgen receptor. Finerenone is claimed to be a more selective blocker of the mineralocorticoid receptor than spironolactone being associated with fewer antiandrogenic side-effects. In this study, we will compare the efficacy, safety and tolerability of finerenone versus spironolactone in patients with hypertension associated with primary aldosteronism.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension; Primary Aldosteronism
• Intervention / Treatment: Drug: Finerenone; Drug: Spironolactone

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ping Li, Ph.D; Phone Number: 86-025-83106666; Email: li78321@yeah.net
• Study Contact Backup: Name: Fan Yang, Ph.D; Phone Number: 86-025-83106666; Email: yangfan_0210@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Age: 18-75 years old.
• 2.History of hypertension, DBP <120 mmHg, SBP <180 mmHg.
• 3.Serum potassium level ≥ 2.5 mmol/L.
• 4.Primary Aldosteronis diagnosed by increased aldosterone renin ratio (ARR) > 30 ng/dl: ng/ml/h, and serum aldosterone levels ≥15 ng / dl, and confirmed by captopril inhibition test.

Exclusion Criteria:

• 1. Abnormal renal function: serum creatinine ≥ 2 × ULN or eGFR ≤ 60 ml/(min * 1.73m2);
• 2. Abnormal liver function: ALT and AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN；
• 3. Cardiac insufficiency, acute myocardial infarction, stroke or other acute cardiovascular events within 6 months;
• 4. Take spironolactone, guanethidine or reserpine 30 days before enrollment;
• 5. Known or suspected tumor; Other autoimmune diseases, uncontrolled infectious diseases, serious respiratory, blood and nervous system diseases;
• 6. There is a pregnancy plan in pregnancy or 3 months before and after treatment. Breast-feeding women;
• 7. Those who have mental illness, alcohol or drug abuse and cannot cooperate with treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Spironolactone	Drug: Spironolactone; The participants were randomized in an equal ratio to receive spironolactone 20 mg twice daily. Patients received the initial dose of study drug for the first 4 weeks of randomized treatment period. Thereafter, the dose of study medication was not changed for patients with adequate BP control. For patients not meeting BP < 140/90 mmHg at week 4, the dose of study medication was increased to spironolactone 40 mg twice daily. If BP > 160/110 mmHg at the time of 8 weeks follow-up, nifedipine 30mg once day was added.
Experimental: Finerenone	Drug: Finerenone; The participants were randomized in an equal ratio to receive finerenone 10 mg once daily. Patients received the initial dose of study drug for the first 4 weeks of randomized treatment period. Thereafter, the dose of study medication was not changed for patients with adequate BP control. For patients not meeting BP < 140/90 mmHg at week 4, the dose of study medication was increased to finerenone 20 mg once daily. If BP > 160/110 mmHg at the time of 8 weeks follow-up, nifedipine 30mg once day was added.; Other Names: Kerendia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypertension remission rate.	The proportion of patients with blood pressure<140/90 mmHg at 12 weeks.	12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of systolic and diastolic BP from the baseline level.	To compare the antihypertensive effect of finerenone versus spironolactone and to establish the noninferiority of finerenone by measuring the mean change from baseline to the week 16 endpoint in end- of-dose (trough) seated DBP.	Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks.
Change of serum potassium level	Change of serum potassium level (mmol/L)	Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks.
Changes of plasma renin activity and ARR.		Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks.
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.
Proportion of patients with normal serum.		Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks.

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: National Natural Science Foundation of China; National Key Research and Development Program of China
• Investigators: Study Director: Ping Li, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: April 3, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: treatment; hypertension; spironolactone; primary aldosteronism; finerenone
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hypertension; Hyperaldosteronism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: PA2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No