Finerenone for Patients With Primary Aldosteronism (FAIRY)

Official title

Finerenone for Patients With Primary Aldosteronism (FAIRY): A Multicenter, Randomized Clinical Trial

Overview

Using spironolactone as the control, to assess the efficacy and safety of finerenone in patients with primary aldosteronism(PA).

Detailed description

This is a multicenter, randomized study designed to evaluate efficacy and safety of finerenone in patients with PA. PA patients are randomly divided into two groups and treated with finerenone or spironolactone for 12 weeks. Spironolactone will be used as the control, while outcome will be assessed after 12-week treatment. Both drugs will be started at 20mg per day, Dose will be adjusted every four weeks to achieve the targeted blood pressure.

Interventions

• Drug Finerenone Oral Tablet
  Eligible patients will be started finerenone at 20mg per day, Dose will be adjusted every four weeks to achieve the targeted blood pressure (the mean office blood pressure \<140/90 mmHg).
• Drug Spironolactone Oral Tablet
  Eligible patients will be started spironolactone at 20mg per day, Dose will be adjusted every four weeks to achieve the targeted blood pressure (the mean office blood pressure \<140/90 mmHg).

Primary outcome measures

• Change from baseline in 24-hour SBP [Time frame: 12 weeks]

Secondary outcome measures (9)

• Change from baseline in 24-hour DBP [Time frame: 12 weeks]
• Change from baseline in daytime SBP [Time frame: 12 weeks]
• Change from baseline in daytime DBP [Time frame: 12 weeks]
• Change from baseline in nighttime SBP [Time frame: 12 weeks]
• Change from baseline in nighttime DBP [Time frame: 12 weeks]
• Blood pressure control rate at the end of the study [Time frame: 12 weeks]
• Serum potassium [Time frame: 12 weeks]
• Hypokalemia control rate at the end of the study [Time frame: 12 weeks]
• Plasma renin concentration [Time frame: 12 weeks]

Eligibility criteria

Inclusion criteria

• . Aged between 18-75, male or female;
• . With confirmed PA diagnosis (screening positive and at least one confirmatory test is positive); NOTE: Screening positive was defined as plasma aldosterone-to-renin ratio (ARR)

≥ 20(pg/ml)/(μIU/ml) or ARR≥30(ng/dL)/(ng/ml/hr). Plasma aldosterone concentration (PAC) post captopril challenge test (CCT) ≥ 110 pg/ml or PAC post seated saline infusion test (SSIT) ≥ 80 pg/ml was considered positive. Note: ARR≥10(pg/ml)/(μIU/ml) or ARR≥15(ng/dL)/(ng/ml/hr) can be considered positive if the patients with hypokalemia (serum potassium < 3.5mmol/L) or adrenal nodules (diameter > 1cm).

• . Not taking any antihypertensive drugs or on a stable regimen of antihypertensive agents(Limited to alpha-adrenergic receptor blockers and calcium channel blockers.) for more than four weeks before screening;
• . With a mean seated office SBP≥140 or DBP≥90 mmHg;
• . Able and willing to give informed consent for participation in the clinical study;

Exclusion criteria

• Has a plan to conduct PA subtype classification(eg. Adrenal vein sampling, PET-CT) in 3 months；
• Has planned surgery within 3 months;
• With a mean seated office SBP ≥ 180mmHg or DBP ≥ 110mmHg before randomization; Note: Mean seated BP is defined as the average of 3 seated BP measurements at any single clinical site visit. If the patient did not take their regularly scheduled antihypertensive medications prior to the visit, 1 BP re-test is allowed within 2 days after taking the medications.
• Night shift workers;
• Has a body mass index(BMI) ≥30 kg/m2 at screening;
• Has uncontrolled diabetes with fasting blood glucose(FBG)≥13.3mmol/L at screening;
• Has uncontrolled chronic diseases;
• Has known other secondary hypertension (eg, renal artery stenosis, Cushing's syndrome, pheochromocytoma, or aortic coarctation) except subclinical Cushing's syndrome;
• Has known and documented heart failure (New York Heart Association (NYHA) class III or IV), liver transaminase levels were more than 2 times higher than the upper limit of normal;
• Has had CABG or other major cardiac surgery (eg, valve replacement), peripheral arterial bypass surgery, or PCI within 6 months before Screening;
• Has had a stroke, transient ischemic attack, hypertensive encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before screening;
• Has poor compliance that can not fully participating in the study;
• Has hyperkalemia with serum potassium > 5.0mmol/L without potassium supplementation;
• Has a history of uncontrolled malignant tumor;
• Has more than 20mmHg difference of seated office SBP in both arms;
• Is not willing or not able to stop taking sex hormones, glucocorticoids, non-steroidal anti-inflammatory drugs, cyclosporine, tacrolimus, or antidepressants;
• Is pregnant, breastfeeding, or planning to become pregnant during the study;
• Complicated with severe mental illness;
• Has had prior solid organ transplant and/or cell transplants;
• Has a history of allergy to Finerenone or spironolactone;
• Has typical consumption of ≥15 alcoholic drinks weekly. Note: 1 drink of alcohol is equivalent to 360ml beer, 45ml spirits, or 150ml wine;
• Has participated in another clinical study involving any investigational drug within 30 days prior to screening；
• Female of childbearing potential refuses to use non-hormonal contraception methods during the study period;
• Refuse to stop eating grapefruit or grapefruit juice during treatment with Finerenone;
• Other situations that the investigator assesses the subject as unable to complete the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the first affiliated hospital of Chongqing medical university — Chongqing

Publications

• Rehan M, Raizman JE, Cavalier E, Don-Wauchope AC, Holmes DT. Laboratory challenges in primary aldosteronism screening and diagnosis. Clin Biochem. 2015 Apr;48(6):377-87. doi: 10.1016/j.clinbiochem.2015.01.003. Epub 2015 Jan 22. PMID 25619896
• Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2. PMID 26934393
• Menard J. The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52. doi: 10.1016/j.mce.2003.10.008. PMID 15134800
• Vilela LAP, Almeida MQ. Diagnosis and management of primary aldosteronism. Arch Endocrinol Metab. 2017 May-Jun;61(3):305-312. doi: 10.1590/2359-3997000000274. PMID 28699986
• Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, Kolkhof P, Kim SY, Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013 Aug;34(31):2453-63. doi: 10.1093/eurheartj/eht187. Epub PMID 23713082
• Agarwal R, Ruilope LM, Ruiz-Hurtado G, Haller H, Schmieder RE, Anker SD, Filippatos G, Pitt B, Rossing P, Lambelet M, Nowack C, Kolkhof P, Joseph A, Bakris GL. Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes. J Hypertens. 2023 Feb 1;41(2):295-302. doi: 10.1097/HJH.0000000000003330. Epub 2022 Dec 8. PMID 36583355
• Agarwal R, Pitt B, Palmer BF, Kovesdy CP, Burgess E, Filippatos G, Malyszko J, Ruilope LM, Rossignol P, Rossing P, Pecoits-Filho R, Anker SD, Joseph A, Lawatscheck R, Wilson D, Gebel M, Bakris GL. A comparative post hoc analysis of finerenone and spironolactone in resistant hypertension in moderate-to-advanced chronic kidney disease. Clin Kidney J. 2022 Oct 30;16(2):293-302. doi: 10.1093/ckj/sfac2 PMID 36864892
• Filippatos G, Anker SD, Agarwal R, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Schloemer P, Tornus I, Joseph A, Bakris GL; FIDELIO-DKD Investigators. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. Circulation. 2021 Feb 9;143(6):540-552. doi: 10.1161/CIRCULATIONAHA.120.051898. Epub 2020 Nov 16. PMID 33198491

Identifiers

NCT: NCT06457074 · FAIRY Study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗