A Biomarker-targeted Clinical Trial to Optimize Treatment for Patients With Chronic Kidney Disease

Официальное название

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

Обзор

Over 800 million people worldwide suffer from chronic kidney disease (CKD), which is associated with a high individual disease burden for those affected, multiple secondary diseases, frequent doctor contacts, and hospitalizations, but also outstanding costs for the health system and the solidarity community. Appropriate interventions are essential to prevent the development and progression of CKD. In the past decade, great progress has been made in the search for drugs that can slow the progression of CKD. Sodium-glucose co-transporter 2 inhibitors, the non-steroidal mineralocorticoid receptor antagonist, finerenone, and the glucagon-like peptide-1 receptor agonist, semaglutide, have demonstrated albuminuria-lowering effects and kidney protection in people with CKD. Although these new pharmacological approaches show great promise, it is unclear how to optimally sequence and combine these therapies. In addition, the therapies are often not implemented due to treatment inertia and fear of adverse effects. This study aims to address this knowledge gap by utilizing a biomarker-guided treatment approach to reduce the decline in kidney function. The aim of the CKD-bioMatch study is to evaluate the efficacy of a biomarker-targeted treatment approach versus standard of care in people with CKD and albuminuria. We hypothesize that a biomarker-targeted treatment approach is superior to standard of care at reducing estimated glomerular filtration rate (eGFR) decline in people with CKD.

Подробное описание

The study is a prospective, randomized, open-label, parallel-group, multicenter study. CKD-bioMatch will enroll 125 individuals with CKD (eGFR ≥ 25 mL/min/1.73m² and UACR 100-5000 mg/g). Participants will be randomized 1:1 to a biomarker-targeted treatment approach versus standard of care.

In the treatment arm, a sequence of pharmacological treatments will be added (dapagliflozin, finerenone, and/or semaglutide), guided by the participant's characteristics and the urinary biomarkers urinary albumin-to-creatinine ratio (UACR) and urinary epidermal growth factor (UEGF). Participants will start treatment with one of the three study medications. After approximately four weeks on the maximum tolerated dose of the allocated medication, UACR and UEGF will be measured, and based on the biomarker response, a decision will be made to continue, switch, or add a new treatment. If a second drug is initiated, the treatment effect of that second drug will be evaluated on UACR and UEGF after four weeks on the maximum tolerated dose, and if the UACR response is insufficient, a third drug can be added, or the third drug can replace the second drug. The biomarker response of the third drug will be evaluated in the same manner as that of the first two drugs.

Вмешательства

• Препарат Dapagliflozin
  Dapagliflozin 10 mg daily.
• Препарат Semaglutide
  Semaglutide injection once weekly. Will be titrated every 4 weeks to the highest tolerable dose according to standard guidelines, aiming at 1 mg once weekly.
• Препарат Finerenone
  Finerenone 10-20 mg daily.

Первичные конечные точки

• Chronic eGFR slope [Срок оценки: From week 26 to 104]

Вторичные конечные точки (3)

• Change in eGFR from baseline to end of study [Срок оценки: From baseline to week 112]
• Change in eGFR from baseline to end of treatment. [Срок оценки: From baseline to week 104]
• Change in UACR [Срок оценки: From baseline to week 104]

Критерии участия

Критерии включения

• Age ≥ 18 and ≤ 75 years
• 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.)
• 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.)
• Ability to communicate with the study staff and understand and sign the informed consent.

Критерии исключения

• eGFR < 25 mL/min/1.73m2 at screening.
• Treatment with two or all three of the study drugs
• History of pancreatitis at screening
• Body mass index < 18.5 kg/m2 at screening
• Type 1 diabetes
• Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrollment
• NYHA class IV Congestive Heart Failure at screening
• Potassium > 5.0 mmol/L at screening
• Addison's Disease
• Concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, cobicistat, clarithromycin)
• Treatment with a potassium-sparing diuretic or a mineralocorticoid receptor antagonist, except for finerenone (e.g., spironolactone, eplerenone, or amiloride)
• 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).
• Autosomal dominant or autosomal recessive polycystic kidney disease
• Lupus nephritis or ANCA-associated vasculitis, or any other primary or secondary kidney disease requiring immunosuppressive therapy within 6 months prior to screening
• Kidney transplant or dialysis
• Known or suspected hypersensitivity to the study medications or related products
• Presence or history of malignant neoplasms (except basal cell skin cancer or squamous cell skin cancer) within five years before screening.
• Any other history, condition, therapy, or uncontrolled intercurrent illness that could, as judged by the investigator, affect participant safety or compliance with study requirements.
• 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.
• Known or suspected abuse of narcotics.
• Participant in another intervention study.
• Vulnerable (i.e., under guardianship) or mentally incapacitated subjects (i.e., not able to understand and sign the informed consent).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Дания · 1 центр

• Steno Diabetes Center Copenhagen — Herlev

Германия · 1 центр

• University Medical Center Hamburg-Eppendorf — Hamburg

Испания · 1 центр

• Hospital Clinico de Valencia — Valencia

Швеция · 1 центр

• Lund University — Malmö

Идентификаторы

NCT: NCT07239570 · 2023-507449-27

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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