Biomarker-guided treatment strategy for chronic kidney disease

A Biomarker-targeted Clinical Trial to Optimize Treatment for Patients With Chronic Kidney Disease: A Prospective, Randomized, Open-Label, Parallel-Group, Multicenter Study

This trial will test whether using urine biomarkers to guide adding dapagliflozin, finerenone, and/or semaglutide can better reduce albuminuria and protect kidneys in adults with CKD.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 125 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Steno Diabetes Center Copenhagen (other)
• Locations: 4 sites (Herlev and 3 other locations)
• Trial ID: NCT07239570 on ClinicalTrials.gov

What this trial studies

CKD-bioMatch is a prospective, randomized, open-label, parallel-group, multicenter study that will enroll 125 adults with CKD and elevated albuminuria and randomize them 1:1 to biomarker-targeted treatment versus standard of care. In the biomarker arm, participants begin one of three medications (dapagliflozin, finerenone, or semaglutide) and have urinary albumin-to-creatinine ratio (UACR) and urinary epidermal growth factor (UEGF) measured after approximately four weeks on the maximum tolerated dose. Based on the biomarker response, clinicians will decide to continue, switch, or add another study medication and repeat the four-week biomarker evaluation for each change. The comparator arm receives usual guideline-based care, and the study compares biomarker-guided sequencing to standard practice across several European centers.

Who should consider this trial

Good fit: Adults aged 18–75 years with CKD, eGFR >= 25 mL/min/1.73 m2, UACR 100–5000 mg/g (with some allowance for historical values), and on stable ACE inhibitor or ARB therapy are ideal candidates.

Not a fit: Patients with eGFR < 25 mL/min/1.73 m2, type 1 diabetes, history of pancreatitis, BMI < 18.5 kg/m2, recent major cardiac events, or already treated with two or more of the study drugs are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could personalize and speed selection of effective therapies to lower albuminuria and slow CKD progression.

How similar studies have performed: Large randomized trials have shown kidney-protective effects for SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists, but using urine biomarkers to guide sequencing and combination of these drugs is largely novel and untested in randomized settings.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75 years
2. UACR 100-5000 mg/g (11.3-565 mg/mmol) in two consecutive first-morning void urine samples at screening. (UACR 80-100 mg/g is accepted if historical measurements are above 100 mg/g and if it cannot be explained by any new treatment.)
3. Stable treatment with a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least four weeks prior to randomization. (Unless such treatment is contraindicated or not tolerated.)
4. Ability to communicate with the study staff and understand and sign the informed consent.

Exclusion Criteria:

1. eGFR \< 25 mL/min/1.73m2 at screening.
2. Treatment with two or all three of the study drugs
3. History of pancreatitis at screening
4. Body mass index \< 18.5 kg/m2 at screening
5. Type 1 diabetes
6. Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrollment
7. NYHA class IV Congestive Heart Failure at screening
8. Potassium \> 5.0 mmol/L at screening
9. Addison's Disease
10. Concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, cobicistat, clarithromycin)
11. Treatment with a potassium-sparing diuretic or a mineralocorticoid receptor antagonist, except for finerenone (e.g., spironolactone, eplerenone, or amiloride)
12. Elevated Alanine Aminotransferase (ALT) \> 3 x upper normal limit at screening, autoimmune hepatitis, and/or severe hepatic impairment (including but not limited to a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt).
13. Autosomal dominant or autosomal recessive polycystic kidney disease
14. Lupus nephritis or ANCA-associated vasculitis, or any other primary or secondary kidney disease requiring immunosuppressive therapy within 6 months prior to screening
15. Kidney transplant or dialysis
16. Known or suspected hypersensitivity to the study medications or related products
17. Presence or history of malignant neoplasms (except basal cell skin cancer or squamous cell skin cancer) within five years before screening.
18. Any other history, condition, therapy, or uncontrolled intercurrent illness that could, as judged by the investigator, affect participant safety or compliance with study requirements.
19. A female who is pregnant, breastfeeding, or intends to become pregnant, or a woman of childbearing potential (WOCBP) who is not using highly effective contraceptive methods.
20. Known or suspected abuse of narcotics.
21. Participant in another intervention study.
22. Vulnerable (i.e., under guardianship) or mentally incapacitated subjects (i.e., not able to understand and sign the informed consent).

Where this trial is running

Herlev and 3 other locations

• Steno Diabetes Center Copenhagen — Herlev, Denmark (RECRUITING)
• University Medical Center Hamburg-Eppendorf — Hamburg, Germany (NOT_YET_RECRUITING)
• Hospital Clinico de Valencia — Valencia, Spain (NOT_YET_RECRUITING)
• Lund University — Malmö, Sweden (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Peter Rossing

Conditions: Chronic Kidney Disease, Personalized medicine, Biomarkers