Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in T2D and CKD (FIVE-STAR) (FIVE-STAR)

Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in Type 2 Diabetes and Chronic Kidney Disease (FIVE-STAR)

To evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in patients with type 2 diabetes and chronic kidney disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Diseases; Type 2 Diabetes
• Intervention / Treatment: Drug: Finerenone; Drug: Placebo

Detailed Description

Finerenone is a novel non-steroidal selective mineralocorticoid receptor antagonist (MRA), characterized by a higher selectivity and affinity for mineralocorticoid receptors than conventional steroidal MRA. In the international phase III trials (FIDELIO-DKD and FIGARO-DKD), finerenone reduced the risk of progression of nephropathy and cardiovascular events in chronic kidney disease (CKD) patients with type 2 diabetes (T2D) who had been on standard treatment for CKD and T2D. However, the possible mechanistic insights into clinical benefits of finerenone in that patient population are currently very limited. To address them, in this investigator-initiated, multicenter, placebo-controlled, randomized trial (FIVE-STAR), the investigators seek to assess the effects of finerenone on vascular stiffness and cardiorenal biomarkers in patients with T2D and CKD.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Koichi Node, MD, PhD; Phone Number: +81-952-34-2364; Email: node@cc.saga-u.ac.jp

Study Locations

• Japan
  • Saga, Japan, 849-8501
    • Saga University Hospital
    • Contact: Atsushi Tanaka, MD, PhD; Phone Number: +81-952-34-2364; Email: tanakaa2@cc.saga-u.ac.jp

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients who have given their written consent to participate in this study
• Patients who are 20 years of age or older at the time of consent (regardless of gender)
• Patients with type 2 diabetes mellitus
• 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.
• Patients who have not changed their medications for type 2 diabetes and chronic kidney disease in the past 4 weeks prior to obtaining consent

Exclusion Criteria:

• Patients who are currently taking or have taken MRAs containing finerenone in the past 4 weeks prior to obtaining consent.
• Patients with a history of hypersensitivity to finerenone
• Patients with HbA1c greater than 10%.
• Patients with a serum potassium level of 4.9 mEq/L or higher
• Patients with NYHA class II-IV HFrEF (LVEF <35%)
• Patients with poorly controlled hypertension (e.g., systolic BP >170 mmHg, diastolic BP >110 mmHg, or hypertensive emergencies)
• 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
• Patients with a preplanned surgical or percutaneous intervention for coronary artery reconstruction or other cardiovascular disease during the individual observation period.
• Patients with a preplanned treatment such as electrical cardioversion, cardiac resynchronization therapy or pacemaker implantation during the individual observation period.
• Patients with preplanned dialysis or kidney transplantation during the individual observation period.
• Patients with severe hepatic dysfunction (Child-Pugh Class C)
• Patients receiving itraconazole, ritonavir-containing products, atazanavir, darunavir, fosamprenavir, cobicistat-containing products, or clarithromycin, or ensitrelvir
• Patients with Addison's disease
• Patients with active infectious diseases
• Pregnant, possibly pregnant, or lactating patients
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo tablets	Drug: Placebo; 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. 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.
Experimental: Finerenone; Kerendia® tablets	Drug: Finerenone; 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. 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.; Other Names: Kerendia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CAVI	Change in CAVI at 24 weeks after initiation of protocol treatment compared to baseline	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in UACR	Proportional changes in geometric mean of UACR at 12 and 24 weeks post-protocol treatment compared to baseline (key secondary endpoint)	12 weeks, 24 weeks
Change in pentosidine	Proportional changes in geometric mean of pentosidine at 24 weeks post-protocol treatment compared to baseline	24 weeks
Change in urinary type IV collagen	Proportional changes in geometric mean of urinary type IV collagen at 24 weeks post-protocol treatment compared to baseline	24 weeks
Change in urinary alpha1-MG	Proportional changes in geometric mean of urinary alpha1-MG at 24 weeks post-protocol treatment compared to baseline	24 weeks
Change in urinary beta2-MG	Proportional changes in geometric mean of urinary beta2-MG at 24 weeks post-protocol treatment compared to baseline	24 weeks
Change in urinary NGAL	Proportional changes in geometric mean of urinary NGAL at 24 weeks post-protocol treatment compared to baseline	24 weeks
Change in urinary NAG	Proportional changes in geometric mean of urinary NAG at 24 weeks post-protocol treatment compared to baseline	24 weeks
Change in urinary L-FABP	Proportional changes in geometric mean of urinary L-FABP at 24 weeks post-protocol treatment compared to baseline	24 weeks

Collaborators and Investigators

• Sponsor: Saga University
• Investigators: Principal Investigator: Koichi Node, MD, PhD, Saga University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): June 5, 2023

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Vascular Stiffness; Finerenone
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Diabetes Mellitus; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 00002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No