Effect of Treatment With Finerenone on Cardio-Renal Target Organ Damage in Patients With Type 2 Diabetes.

Official title

Effect of Treatment With Finerenone on Cardio-Renal Target Organ Damage in Patients With Type 2 Diabetes - A Randomized Trial

Overview

The global prevalence of diabetes is increasing substantially. Around 40 % of patients with type 2 diabetes develop chronic kidney disease. Diabetic kidney disease is the leading cause of kidney failure, it is closely linked to cardiovascular disease and heart failure and is associated with a threefold increase in all-cause mortality and a 16-year loss in life expectancy. In large clinical trials, the novel drug finerenone has shown to lower the risk of chronic kidney disease progression and improve the cardiovascular outcome for patients with type 2 diabetes and chronic kidney disease. However these trials did not not reflect current standard-of-care for patients with type 2 diabetes and chronic kidney disease, as only a minority (6.7 %) received an SGLT2-I - a treatment that has been considered standard-of-care for these patients since 2022. The FineCaRe study aims to investigate the effect of treatment with finerenone in combination with an SGLT2-I on albuminuria and left ventricular mass in patients with type 2 diabetes and chronic kidney disease. The investigators will perform a 26-week investigator-initiated, single-center, placebo-controlled, double-blinded randomized clinical trial. After screening and inclusion, participants will be randomized 1:1 to either finerenone or placebo treatment. Outcomes will be assessed at baseline, during and after 26 weeks of treatment. The primary goal of the FineCaRe study is to acquire new knowledge that may help in preventing kidney failure in diabetic patients. With this project the investigators aim to contribute to the understanding of which disease mechanisms in the kidneys and heart that can be targeted in diabetic patients with kidney disease. This could hopefully provide better opportunities for preventing chronic kidney disease and kidney failure.

Interventions

• Drug Finerenone (BAY 94-8862)
  Patients with an eGFR of 25-60 ml/min/1.73m2 will receive an initial dose of 10 mg finerenone/placebo once daily and those with an eGFR of at least 60 ml/ in/1.73m2 will receive an initial dose of 20 mg finerenone/placebo once daily. From 4 weeks the target dose is 20 mg finerenone/placebo once daily. An increase in dose from 10 to 20 mg once daily will be encouraged after 4 weeks provided the plasma potassium level is 4.8 mmol/L or less and the eGFR stable. If eGFR is reduced with \>30 % compar
• Drug Placebo
  Placebo tablets matching BAY94-8862 are administered orally.

Primary outcome measures

• Change in left ventricular mass measured by non-contrast cardiac MRI of the heart [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in albuminuria measured by a urinary albumin-to-creatinine ratio (UACR) in morning spot urine samples (first morning voids). [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]

Secondary outcome measures (12)

• Change in the rate of myocardial fibrosis (extracellular cardiac volume - ECV %) measured by MRI of the heart using gadolinium-containing contrast. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in the rate of myocardial fibrosis measured by non-contrast T1-mapping using MRI of the heart. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in left ventricular ejection fraction (EF), left ventricular and atrial volumes measured by non-contrast MRI of the heart. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in thoracic aortic wall volume (TWV) measured by MRI of the heart. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in the rate of pulse wave velocity in the aorta measured by non-contrast MRI of the heart. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in arterial stiffness assessed as cf-PWV. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in 24-hour blood pressure. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in inflammatory and fibrotic biomarkers related to CVD measured in blood and urine. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in measured glomerular filtration rate (mGFR) assessed by injection of a tracer. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in eGFR slope including all available outpatient eGFR measured a) from before treatment to last day of treatment b) from 4 weeks after treatment initiation to last day after treatment. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in UACR by repeated measures analysis including all available outpatient UACR measurements from before treatment to the last day after treatment. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]
• Change in markers of the RAAS measured in blood and urine. [Time frame: From the baseline visit at week 0 to the end of treatment at week 26.]

Eligibility criteria

Inclusion criteria

• Age above 18 years.
• Diagnosis of type 2 diabetes according to the World Health Organization definition.
• Current treatment with a SGLT2-I1 at maximally tolerated dose.
• Current treatment with an ACE inhibitor or an ARB1 at maximally tolerated dose.
• Plasma potassium level of 4.8 mmol/L or less at the time of screening.
• CKD defined as eGFR ≥25 ml/min/1.73 m2 and albuminuria (UACR between 30-5000 mg/g).
• Speak and understand Danish fluently.

Exclusion criteria

• Inability to give informed consent.
• Severe renal disease with eGFR <25 ml/min/1.73m2.
• Severe hepatic disease (plasma ALAT above 3 x upper limit of normal).
• Active cancer diagnosis other than basal cell carcinoma.
• Treatment with systemic steroids at time of randomization.
• Bariatric surgery within 2 years or other gastrointestinal surgeries that induce chronic malabsorption.
• Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake.
• Chronic or acute pancreatitis.
• Pregnancy or breastfeeding (see pregnancy below).
• Poorly controlled medical condition, e.g. congestive heart failure (New York Heart Association III-IV or EF ≤ 40%), recent (within 3 months) stroke or acute myocardial infarction or any other condition that in the opinion of the investigator will put the trial participant at risk if participating in the trial.
• Allergy to finerenone or any of the excipients contained in the drug.
• Current systemic treatment with strong inhibitors of CYP3A4 (e.g. itraconazol, ketoconazole, ritonavir, cobicistat, clarithromycin) or strong inducers of CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital).
• Current treatment with other MRAs (e.g. spironolactone, eplerenone etc.).
• Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption.
• Addison's disease.
• Contraindications to MRI.
• Previous renal or heart transplantation.

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

Quadruple blind

Primary purpose

Treatment

Study locations

Denmark · 1 center

• Steno Diabetes Center Aarhus — Aarhus N

Identifiers

NCT: NCT07026539 · 20235044465800 · 2023-504446-58-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗