Clinical trial NCT07026539: Effect of Treatment With Finerenone on Cardio-Renal Target Organ Damage in Patients With Type 2 Diabetes - A Randomized Trial
Official title: Effect of Treatment With Finerenone on Cardio-Renal Target Organ Damage in Patients With Type 2 Diabetes - A Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus (T2DM)
Chronic Kidney Disease Due to Type 2 Diabetes Mellitus
Cardiovascular Diseases
Keywords: Mineralocorticoid receptor antagonist (MRA)
Type 2 diabetes
Chronic kidney disease
Diabetic complications
finerenone
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2025-06-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

We will perform a 26-week investigator-initiated, single-center, placebo-controlled, double-blinded randomized clinical trial. After screening and inclusion, patients 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 we 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.


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.

Primary outcomes:
measure: Change in left ventricular mass measured by non-contrast cardiac MRI of the heart
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in albuminuria measured by a urinary albumin-to-creatinine ratio (UACR) in morning spot urine samples (first morning voids).
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
Secondary outcomes:
measure: Change in the rate of myocardial fibrosis (extracellular cardiac volume - ECV %) measured by MRI of the heart using gadolinium-containing contrast.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in the rate of myocardial fibrosis measured by non-contrast T1-mapping using MRI of the heart.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in left ventricular ejection fraction (EF), left ventricular and atrial volumes measured by non-contrast MRI of the heart.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in thoracic aortic wall volume (TWV) measured by MRI of the heart.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in the rate of pulse wave velocity in the aorta measured by non-contrast MRI of the heart.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in arterial stiffness assessed as cf-PWV.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in 24-hour blood pressure.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in inflammatory and fibrotic biomarkers related to CVD measured in blood and urine.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in measured glomerular filtration rate (mGFR) assessed by injection of a tracer.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: 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.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in UACR by repeated measures analysis including all available outpatient UACR measurements from before treatment to the last day after treatment.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in markers of the RAAS measured in blood and urine.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in inflammatory and fibrotic biomarkers related to CKD (e.g. markers of renal tubule damage) measured in blood and urine.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in kidney microstructure and fibrosis assessed as changes in T1-mapping and changes in the rate of ADC-values of diffusion-weighted MRI of the kidneys using non-contrast MRI.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in renal oxygenation assessed by BOLD MRI and change in renal perfusion with a pseudo continuous arterial spin labeling (pCASL), both non-contrast MR techniques
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in kidney size measured by a Dixon water/fat sequence MRI, a non-contrast MRI technique.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
Other outcomes:
measure: Change in retinal thickness assessed with Optical Coherence Tomography (OCT).
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in retinal oxygenation measured by oximetry.
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
measure: Change in the transcriptomic, proteomic, and/or metabolomic profile in plasma and urine. Furthermore, to test if possible changes can be related to pathways involved in and/or serve as biomarkers of the progression of cardiovascular and/or kidney disease
timeFrame: From the baseline visit at week 0 to the end of treatment at week 26.
Locations:
city: Aarhus N
country: Denmark
facility: Steno Diabetes Center Aarhus
Study officials:
References: