Effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease

JRCT ID: jRCTs021230011

Registered date:22/06/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: type 2 diabetes and chronic kidney disease
• Date of first enrollment: 22/06/2023
• Target sample size: 100
• Study type: Interventional

Intervention(s)

After confirming the eligibility of patients whose written consent has been obtained, patients who meet all inclusion criteria will be enrolled. Patients will be randomized (assigned) to one of two groups, the finerenone group or the placebo group, and will be administered the medication, observation, and prescribed tests at baseline (before the start of study drug administration), 4, 12, and 24 weeks under double-blind conditions. In principle, baseline testing will be conducted within 60 days of obtaining consent, and study drug dosing will begin the day after that.
Study participants will be instructed to take either finerenone or placebo orally once daily (preferably at approximately the same time every during the morning). For study participants with baseline eGFR less than 60mL/min/1.73 m2, the starting dose will be 10mg/day of finerenone (equivalent to 10mg/day in the placebo group), followed by 20 mg/day (equivalent to 20mg/day in the placebo group) approximately 4 weeks after the first dose, in accordance with the latest package insert. The dose should be increased to 20mg/day (equivalent to 20mg/day in the placebo group) in principle after 4 weeks from the start of the first dose, in accordance with the latest package insert. In addition, study participants with a baseline eGFR of 60 mL/min/1.73m2 or higher will receive 20mg/day of finerenone (equivalent to 20mg/day in the placebo group) as the starting dose.

Outcome(s)

• Primary Outcome: Change in CAVI at 24 weeks after initiation of protocol treatment compared to baseline

Secondary Outcome

1. Proportional changes in geometric mean of UACR at 12 and 24 weeks post-protocol treatment compared to baseline (key secondary endpoint)
2. Proportional changes in geometric mean of blood biomarkers (pentosidine) and urinary biomarkers (type IV collagen, alpha1-MG, beta2-MG, NGAL, NAG, L-FABP creatinine ratio) at 24 weeks post-protocol treatment compared to baseline

<Other endpoints
1. Change from baseline in vital signs (weight, BMI, eEV, blood pressure/pulse pressure/pulse rate in the office, and blood pressure/pulse pressure/pulse rate at home) at 4, 12, and 24 weeks after the start of protocol treatment
2. Change from baseline in blood collection indices (serum creatinine, eGFR, serum cystatin C*, serum potassium, HbA1c*, plasma (or serum) aldosterone concentration**, plasma (or serum) renin activity or concentration**) at 4, 12, and 24 weeks after initiation of protocol treatment (*performed at baseline, 12 and 24 weeks only, **assessed at baseline and evaluated at 24 weeks only)
3. Change from baseline in AI and % mean arterial pressure at 24 weeks after initiation of protocol treatment
4. Change from baseline in cardiac function indices (LVEF, septal e', lateral e', E, E/e', LVMI, LAD, LAVI) as assessed by echocardiography at 24 weeks post-protocol treatment Change from baseline
5. Change in a total of max 181 proteins analyzed comprehensively by proteomic analysis(Target 96) at 24 weeks after initiation of protocol treatment compared to baseline (exploratory endpoint)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who have given their written consent to participate in this study
2) Patients who are 20 years of age or older at the time of consent (regardless of gender)
3) Patients with type 2 diabetes mellitus
4) Patients with chronic kidney disease who meet both of the following criteria
I. eGFR greater than 25 mL/min/1.73 m2 and less than 90 mL/min/1.73 m2
II. UACR greater than 30 mg/g.cr. and less than 3500 mg/g.cr.
5) Patients who have not changed their medications for type 2 diabetes and chronic kidney disease in the past 4 weeks prior to obtaining consent

Exclude criteria

1) Patients who are currently taking or have taken MRAs containing finerenone in the past 4 weeks prior to obtaining consent.
2) Patients with a history of hypersensitivity to finerenone
3) Patients with HbA1c greater than 10%.
4) Patients with a serum potassium level of 4.9 mEq/L or higher
5) Patients with NYHA class II-IV HFrEF (LVEF <35%)
6) Patients with poorly controlled hypertension (e.g., systolic BP >170 mmHg, diastolic BP >110 mmHg, or hypertensive emergencies)
7) Patients with a history of ischemic stroke, acute coronary syndrome, cardiovascular surgery or percutaneous intervention, or hospitalization for worsening heart or renal failure in the past 8 weeks prior to obtaining consent
8) Patients with a preplanned surgical or percutaneous intervention for coronary artery reconstruction or other cardiovascular disease during the individual observation period.
9) Patients with a preplanned treatment such as electrical cardioversion, cardiac resynchronization therapy or pacemaker implantation during the individual observation period.
10) Patients with preplanned dialysis or kidney transplantation during the individual observation period.
11) Patients with severe hepatic dysfunction (Child-Pugh Class C)
12) Patients receiving itraconazole, ritonavir-containing products, atazanavir, darunavir, fosamprenavir, cobicistat-containing products, or clarithromycin, or ensitrelvir
13) Patients with Addison's disease
14) Patients with active infectious diseases
15) Pregnant, possibly pregnant, or lactating patients
16) Other patients deemed inappropriate for this study by the principal investigator or subinvestigators (e.g., patients with renal artery stenosis, one kidney, or active malignancy).

Related Information

• Primary Sponsor: Node Koichi
• Source(s) of Monetary Support: Bayer Yakuhin, Ltd.
• Secondary ID(s): NCT05887817