Finerenone for Type 2 diabetes mellitus | Chronic kidney disease

Inclusion criteria

• {"criterion_text":"- Diagnosis of type 2 diabetes according to the World Health Organization definition\n- Chronic kidney disease defined as eGFR ≥ 25 ml/min/1.73 m2 and elevated albuminuria (urinary albumin-to-creatine ratio of 30-5000 mg/g).\n- Current treatment with an sodium-glucose-cotransporter 2 (SGLT2)-inhibitor at maximally tolerated dose\n- Current treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) at maximally tolerated dose\n- Serum potassium level of 4.8 mmol/L or less at the time of screening\n- Age above 18 years\n- Speak and understand Danish fluently"}

Exclusion criteria

• {"criterion_text":"- Inability to give informed consent\n- Severe hepatic disease (serum ALAT above 3x upper limit of normal)\n- Active cancer diagnosis other than basal cell carcinoma\n- Treatment with systemic steroids at time of randomization.\n- Bariatric surgery within 2 years or other gastrointestinal surgeries that induce chronic malabsorption.\n- 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.\n- Chronic or acute pancreatitis.\n- Pregnancy or breastfeeding\n- Previous renal or heart transplantation\n- 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.\n- Allergy to finerenone or any of the excipients contained in the drug.\n- Current systemic treatment with strong inhibitors of CYP3A4 (e.g. itraconazol, ketocona-zole, ritonavir, cobicistat, clarithromycin) or strong inducers of CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital).\n- Current treatment with other mineralocorticoid receptor antagonists (e.g. spironolactone, eplerenone etc.).\n- Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.\n- Addison’s disease.\n- Contraindications to magnetic resonance imaging (MRI).\n- Severe renal disease with eGFR<25 ml/min/1.73m2"}

Primary endpoints

• {"endpoint_text":"- Change in left ventricular mass measured by non-contrast cardiac MRI.","definition_or_measurement_approach":"Measured by non-contrast cardiac MRI."}
• {"endpoint_text":"- Change in albuminuria measured by urinary albumin-to-creatinine ratio (UACR) in morning spot urine samples (first morning voids).","definition_or_measurement_approach":"Measured as urinary albumin-to-creatinine ratio (UACR) in morning spot urine samples (first morning voids)."}

Secondary endpoints

• {"endpoint_text":"- Change in the rate of myocardial fibrosis (extracellular cardiac volume – ECV %) measured by MRI of the heart using gadolinium-containing contrast.","definition_or_measurement_approach":"Measured by MRI of the heart using gadolinium-containing contrast; extracellular cardiac volume (ECV %) assessment."}
• {"endpoint_text":"- Change in the rate of myocardial fibrosis measured by non-contrast T1-mapping, measured by non-contrast MRI of the heart.","definition_or_measurement_approach":"Measured by non-contrast T1-mapping using non-contrast cardiac MRI."}
• {"endpoint_text":"- Change in left ventricular ejection fraction (EF), left ventricular and atrial volumes measured by non-contrast MRI of the heart.","definition_or_measurement_approach":"Measured by non-contrast cardiac MRI assessing EF and chamber volumes."}
• {"endpoint_text":"- Change in the rate of pulse wave velocity in the aorta measured by non-contrast MRI of the heart.","definition_or_measurement_approach":"Measured by non-contrast MRI assessing aortic pulse wave velocity."}
• {"endpoint_text":"- Change in arterial stiffness assessed as carotid-femoral pulse wave velocity.","definition_or_measurement_approach":"Assessed as carotid-femoral pulse wave velocity (method not further specified)."}
• {"endpoint_text":"- Change in 24-hour blood pressure.","definition_or_measurement_approach":"Measured as change in 24-hour ambulatory blood pressure."}
• {"endpoint_text":"- Change in inflammatory and fibrotic biomarkers related to cardiovascular disease measured in blood and urine.","definition_or_measurement_approach":"Measured via blood and urine biomarker assays for inflammatory and fibrotic markers relevant to cardiovascular disease."}
• {"endpoint_text":"- Change in measured glomerular filtration rate (mGFR) assessed by injection of a tracer.","definition_or_measurement_approach":"mGFR assessed by injection of a tracer (measured GFR methodology)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"eGFR slope computed from outpatient eGFR measurements over specified time intervals (before treatment to last day, and from 4 weeks after initiation to last day)."}
• {"endpoint_text":"- Change in UACR by repeated measures analysis including all available outpatient UACR measurements from before treatment to the last day after treatment.","definition_or_measurement_approach":"UACR change analysed by repeated measures including all outpatient UACR from before treatment to last day after treatment."}
• {"endpoint_text":"- Change in markers of the renin-angiotensin-aldosterone system measured in blood and urine.","definition_or_measurement_approach":"Measured via blood and urine assays for renin-angiotensin-aldosterone system markers."}
• {"endpoint_text":"- Change in inflammatory and fibrotic biomarkers related to chronic kidney disease (e.g. markers of renal tubule damage) measured in blood and urine.","definition_or_measurement_approach":"Measured via blood and urine biomarker assays for renal inflammation and fibrosis (including renal tubule damage markers)."}
• {"endpoint_text":"- Change in kidney microstructure and fibrosis assessed as changes in T1-mapping and changes in the rate of apparent diffusion coefficient (ADC)-values of diffusion-weighted MRI of the kidneys using non-contrast MRI.","definition_or_measurement_approach":"Assessed by non-contrast renal MRI: T1-mapping and ADC values from diffusion-weighted imaging."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessed by non-contrast renal MRI techniques: BOLD MRI for oxygenation and pCASL for perfusion."}
• {"endpoint_text":"- Change in kidney size measured by a Dixon water/fat sequence MRI, a non-contrast MRI technique.","definition_or_measurement_approach":"Measured by Dixon water/fat sequence on non-contrast MRI."}
• {"endpoint_text":"- Change in thoracic aortic wall volume (TWV) measured by MRI of the heart.","definition_or_measurement_approach":"Measured by cardiac MRI assessing thoracic aortic wall volume (TWV)."}

Methods

• Recruitment adverts and postings (Appendix B - Rekrutteringsopslag).
• Newspaper and social media advertising (Appendix C - Annonce til avis_sociale medier).
• Recruitment letters (Appendix E - Rekrutteringsbrev) and e-Boks letters (Appendix D - E-boks brev) sent to potential participants.
• Participant information and informed consent materials provided (Appendix F - Deltagerinformation; Appendix H - Samtykkeerklring).

Denmark

Earliest CTIS Part Ii Submission Date

09-08-2024

Latest Decision Or Authorization Date

03-03-2025

Processing Time Days

206

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Aarhus University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"Sponsor duty code 1","organisation_type":"Educational Institution"}