Comparing Inclisiran Versus Statin for Primary Aldosteronism

NCT07884955 | Recruiting DMC

• 1 other identifier: ISPA
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Primary aldosteronism represents one of the leading causes of resistant hypertension. Circulating cholesterol is established as the exclusive substrate for adrenal aldosterone synthesis, and statins, which suppress cholesterol production, are currently widely applied in clinical settings. Emerging clinical evidence has demonstrated that in patients with essential hypertension, the plasma aldosterone level decreased by 43% (from 13.9 ng/dL to 7.9 ng/dL) after treatment with PCSK9 inhibitors. However, the effect of PCSK9 inhibitors with superior lipid-lowering efficacy combined with amlodipine besylate on aldosterone levels remains elusive. The present clinical trial adopted inclisiran, a PCSK9 inhibitor with well-documented clinical safety and robust lipid-lowering effects, in combination with amlodipine besylate. Through randomized grouping intervention and follow-up, this study aimed to compare the differential effects of two therapeutic regimens-inclisiran-based therapy and statin-based therapy-on plasma aldosterone levels, as well as improvements in a spectrum of clinical parameters including blood pressure , serum potassium and so on in patients with primary aldosteronism. The outcomes of this trial are expected to provide novel and more effective pharmacological strategies for the management of primary aldosteronism.

Conditions

Primary Aldosteronism

Keywords

primary aldosteronism; PCSK9; Statins; Inclisiran

Outcome Measures

Primary Outcomes (1)

• Change from baseline in plasma aldosterone level

  24 weeks after randomization

Secondary Outcomes (6)

• Change from baseline in systolic and diastolic blood pressure

  24 weeks after randomization

• Change from baseline in plasma renin concentration

  24 weeks after randomization

• Change from baseline in 24-hour urinary aldosterone

  24 weeks after randomization

• Change from baseline in serum potassium level

  24 weeks after randomization

• Change from baseline in plasma lipid

  24 weeks after randomization

Study Arms (2)

Subcutaneous inclisiran plus oral amlodipine besylate and spironolactone

EXPERIMENTAL

Participants receive inclisiran subcutaneously plus oral amlodipine besylate and spironolactone

Drug: inclisiran; Drug: Spironolactone (drug); Drug: Amlodipine besylate

Statin plus amlodipine besylate and spironolactone

PLACEBO COMPARATOR

Participants receive statin plus oral amlodipine besylate and spironolactone

Drug: Lipophilic statins (such as Simvastatin, Atorvastatin, Fluvastatin, Lovastatin,Pitavastatin); Drug: Spironolactone (drug); Drug: Amlodipine besylate

Interventions

inclisiran DRUG

Subcutaneous inclisiran

Subcutaneous inclisiran plus oral amlodipine besylate and spironolactone

Spironolactone (drug) DRUG

oral Spironolactone

Statin plus amlodipine besylate and spironolactone; Subcutaneous inclisiran plus oral amlodipine besylate and spironolactone

Lipophilic statins (such as Simvastatin, Atorvastatin, Fluvastatin, Lovastatin,Pitavastatin) DRUG

oral Lipophilic statins (such as Simvastatin, Atorvastatin, Fluvastatin, Lovastatin,Pitavastatin)

Statin plus amlodipine besylate and spironolactone

Amlodipine besylate DRUG

oral Amlodipine besylate

Statin plus amlodipine besylate and spironolactone; Subcutaneous inclisiran plus oral amlodipine besylate and spironolactone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with hypertension aged18-70years.
• Meeting the diagnostic criteria for primary aldosteronism (PA) according to the \*Expert Consensus on the Diagnosis and Treatment of Primary Aldosteronism (2025 Edition)
• Patients either untreated or on antihypertensive therapy; after a 1-2week washout period, blood pressure is \<160/100mmHg.
• Serum potassium at the end of the run-in period: 3mmol/L ≤ serum potassium \<5mmol/L.
• Voluntary participation in the trial and provision of written informed consent.

You may not qualify if:

• Office blood pressure \>180/110mmHg.
• Severe hepatic insufficiency or severe renal insufficiency.
• Acute coronary syndrome, myocardial infarction, percutaneous coronary intervention, or cerebrovascular accident within the previous 6 months; heart failure of NYHA class II-IV.
• Serum potassium \<2.5mmol/L or \>5.5mmol/L.
• Pregnancy or planned pregnancy within 1year.
• Neurological or psychiatric disorders.
• Concurrent malignant neoplasm.
• Low-density-lipoprotein-cholesterol(LDL-C) \<2.6mmol/L.
• Any other conditions that, in the investigator's opinion, may interfere with efficacy and/or safety assessment of the study (including but not limited to poor subject compliance or inability to attend scheduled follow-up due to long-distance residence).

Sponsors & Collaborators

• Third Military Medical University: lead

Study Sites (1)

Daping Hospital,Third Military Medical University

Chongqing, Chongqing Municipality, 400042, China

RECRUITING

Related Publications (5)

• Wu H, He H, Han T, Tian X, Zhu Z. Targeting cholesterol-dependent adrenal steroidogenesis for management of primary aldosteronism. Trends Endocrinol Metab. 2025 Sep;36(9):789-801. doi: 10.1016/j.tem.2024.12.001. Epub 2025 Jan 6.

  PMID: 39765399 BACKGROUND

• Izkhakov E, Shacham Y, Serebro M, Yaish I, Marcus Y, Shefer G, Tordjman K, Greenman Y, Stern N, Ziv-Baran T. The Effect of the PCSK9 Inhibitor Evolocumab on Aldosterone Secretion among High Cardiovascular Risk Patients: A Pilot Study. J Clin Med. 2021 Jun 5;10(11):2504. doi: 10.3390/jcm10112504.

  PMID: 34198795 BACKGROUND

• Navarese EP, Kolodziejczak M, Schulze V, Gurbel PA, Tantry U, Lin Y, Brockmeyer M, Kandzari DE, Kubica JM, D'Agostino RB Sr, Kubica J, Volpe M, Agewall S, Kereiakes DJ, Kelm M. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 Jul 7;163(1):40-51. doi: 10.7326/M14-2957.

  PMID: 25915661 BACKGROUND

• Baudrand R, Pojoga LH, Vaidya A, Garza AE, Vohringer PA, Jeunemaitre X, Hopkins PN, Yao TM, Williams J, Adler GK, Williams GH. Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects. Circulation. 2015 Nov 10;132(19):1825-33. doi: 10.1161/CIRCULATIONAHA.115.016759. Epub 2015 Oct 2.

  PMID: 26432671 BACKGROUND

• Capponi AM. Regulation of cholesterol supply for mineralocorticoid biosynthesis. Trends Endocrinol Metab. 2002 Apr;13(3):118-21. doi: 10.1016/s1043-2760(01)00538-0.

  PMID: 11893525 BACKGROUND

MeSH Terms

Conditions

Hyperaldosteronism

Interventions

ALN-PCS; Simvastatin; Atorvastatin; Fluvastatin; Lovastatin; pitavastatin; Spironolactone; Pharmaceutical Preparations; Amlodipine

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Dihydropyridines; Pyridines

Central Study Contacts

Liyuan Yuan

CONTACT

+8617374960635; 706539967@qq.com

Zhiming Zhu

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Department of Hypertension and Endocrinology

Study Record Dates

• First Submitted: October 13, 2026
• First Posted: October 21, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: October 21, 2026

Record last verified: 2026-10

Locations

CN (1)