Mark Patrick B, De Sousa-Amorim Erika, Eriksson Anna L, Zachrisson Maria L, Guzman Nicolas J, Miller Matthew T, Jiang Yunyun, Heerspink Hiddo J L
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK.
Nephrol Dial Transplant. 2025 Jul 7. doi: 10.1093/ndt/gfaf119.
Despite benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) recommended for treatment of chronic kidney disease (CKD), there is still an unmet need for managing renal residual risk. Based on pre-clinical data, balcinrenone is a novel mineralocorticoid receptor antagonist that maintains cardio-renal benefits without increasing hyperkalaemia risk. Use of balcinrenone and dapagliflozin is expected to provide complementary and additive kidney and cardiovascular protection. The MIRO-CKD study tests the hypothesis that balcinrenone with dapagliflozin is superior to dapagliflozin alone in reducing albuminuria in patients with CKD.
MIRO-CKD is a double-blind, active-controlled, phase 2b study evaluating the efficacy and safety of balcinrenone/dapagliflozin in 300 adults (planned) with CKD, eGFR 25-60 mL/min/1.73m2 and serum potassium within normal range. Participants are being randomized 1:1:1 to balcinrenone/dapagliflozin 15 mg/10 mg, 40 mg/10 mg or placebo/dapagliflozin 10 mg for 12 weeks, followed by an 8-week wash-out period to assess off-drug effects. The primary endpoint is the change in log-transformed urinary albumin-to-creatinine ratio (UACR) from baseline to Week 12. Other outcomes include pharmacokinetics, safety and tolerability.
614 patients were screened and 324 were randomized across 15 countries in Asia, Europe, North and South America. 56.2% of participants were taking SGLT2i and 87.1% renin angiotensin aldosterone system inhibitors at enrolment. The patient population are at increased risk of CKD progression by having CKD stage 3/4 and albuminuria (median UACR: 365.5 mg/g; mean eGFR: 42.2 mL/min/1.73m2). 56.5% of participants had type 2 diabetes mellitus.
MIRO-CKD is a fully recruited global trial enrolling a contemporary CKD population at increased risk of progression and with an increased risk of hyperkalaemia based on their reduced kidney function. The study will assess the efficacy, safety and tolerability of the combination of balcinrenone and dapagliflozin to identify an optimal dose for a future phase 3 study in patients with CKD.
尽管钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）被推荐用于治疗慢性肾脏病（CKD）且具有诸多益处，但在管理肾脏残余风险方面仍存在未满足的需求。基于临床前数据，巴氯烯酮是一种新型盐皮质激素受体拮抗剂，可维持心肾获益而不增加高钾血症风险。联合使用巴氯烯酮和达格列净有望提供互补且累加的肾脏和心血管保护作用。MIRO-CKD研究检验了以下假设：在降低CKD患者蛋白尿方面，巴氯烯酮联合达格列净优于单用达格列净。
MIRO-CKD是一项双盲、活性药物对照的2b期研究，评估巴氯烯酮/达格列净对300名（计划样本量）CKD成人患者的疗效和安全性，这些患者的估算肾小球滤过率（eGFR）为25 - 60 mL/min/1.73m²，血清钾在正常范围内。参与者按1:1:1随机分组，分别接受巴氯烯酮/达格列净15 mg/10 mg、40 mg/10 mg或安慰剂/达格列净10 mg治疗12周，随后有8周的洗脱期以评估停药效应。主要终点是从基线到第12周对数转换后的尿白蛋白与肌酐比值（UACR）的变化。其他结局指标包括药代动力学、安全性和耐受性。
共筛选了614例患者，324例在亚洲、欧洲、南北美洲的15个国家进行了随机分组。入组时，56.2%的参与者正在服用SGLT2i，87.1%正在服用肾素-血管紧张素-醛固酮系统抑制剂。该患者群体因处于CKD 3/4期且有蛋白尿（UACR中位数：365.5 mg/g；平均eGFR：42.2 mL/min/1.73m²）而有CKD进展风险增加的情况。56.5%的参与者患有2型糖尿病。
MIRO-CKD是一项已完成全部入组的全球试验，纳入了一个当代CKD人群，该人群因肾功能降低而有进展风险增加和高钾血症风险增加的情况。该研究将评估巴氯烯酮和达格列净联合用药的疗效、安全性和耐受性，以确定未来针对CKD患者进行3期研究的最佳剂量。
