Safety and Efficacy of Finerenone in Metabolic Dysfunction Associated Steatotic Liver Disease(MASLD/NAFLD) Related Cirrhosis Patients With Ascites in Prevention of Chronic Kidney Disease.

Official title

Safety and Efficacy of Finerenone in Metabolic Dysfunction Associated Steatotic Liver Disease(MASLD/NAFLD) Related Cirrhosis Patients With Ascites in Prevention of Chronic Kidney Disease. A Randomized Control Trial.

Overview

Renal dysfunction is a frequent and clinically important complication in cirrhosis, and MASLD/NAFLD is associated with increased risk of incident CKD; however, finerenone has not been specifically studied in MASLD-cirrhosis populations despite proven cardiorenal benefits in diabetic CKD. This monocentric, open-label, randomized controlled trial at the Department of Hepatology, ILBS, New Delhi will enroll 160 adults (18-80 years) with MASLD/NAFLD cirrhosis, clinical grade I-II ascites, and stable eGFR ≥60 mL/min/1.73 m² (MDRD-6), with key exclusions including CTP class C, refractory ascites, significant coagulopathy, intrinsic kidney disease, recent major cardiovascular events, and other protocol-defined contraindications. Participants will receive standard medical treatment (dietary measures, diuretics as indicated, metabolic control, complication management, albumin/beta-blockers as needed) and will be randomized to finerenone (5 mg/day uptitrated to 10-20 mg/day) versus spironolactone (50 mg/day uptitrated to 100-200 mg/day). The primary endpoint is incident CKD at 6 months , defined as sustained eGFR \<60 mL/min/1.73 m² over 3 months. Secondary endpoints include MAKE/MACE/MALO at 6 months, drug-related adverse events (including hyperkalemia, hyponatremia, hypotension, hyperuricemia), AKI/AKD episodes, renal biomarkers (e.g., cystatin C, UPCR), ascites response, liver severity scores (MELD 3.0/MELD-Na/CTP), and metabolic/inflammatory/endothelial markers (e.g., HbA1c, HOMA-IR, hsCRP, vWF). Sample size (n=160; 80/arm) is powered to detect an absolute 20% reduction in CKD progression (35% to 15%) with 80% power and 5% alpha (10% dropout), with intention-to-treat analyses including Kaplan-Meier and Cox regression methods.

Interventions

• Drug Finerenone
  finerenone 5 mg/day followed by 10 mg/day. Dose will be increased as necessary up to 20mg/day.
• Drug Spironolactone
  Spironolactone 50mg/day followed by 100mg/day,Dose will be increased as necessary up to 200mg/day.
• Other Standard Medical Treatment
  1. Salt restricted diet, high protein diet 2. Patient education 3. Use of loop diuretics as indicated and tolerated 4. Glycemic control in diabetic subjects- SGLT2 inhibitors/DPP4 inhibitors/ GLP-1 analog +/- insulin 5. Managing complications of liver disease 6. Albumin infusions as and when required as per physician's discretion. 7. Use of Beta blockers as indicated and tolerated.

Primary outcome measures

• Incidence of chronic kidney disease (CKD) in patients with MASLD/NAFLD related cirrhosis with clinical ascites at 6 months between both the groups, defined as: [Time frame: 6 months]

Secondary outcome measures (6)

• Incidence of hyperkalemia/hyponatremia/hypotension/hyperuricemia. [Time frame: 6 months]
• Incidence of Acute Kidney Injury (AKI) - Number and proportion of participants developing Acute Kidney Injury - Based on KDIGO criteria (increase in serum creatinine ≥0.3 mg/dL in 48 hours or ≥1.5× baseline within 7 days) . [Time frame: 6 months]
• Incidence of Acute Kidney Disease (AKD) - Number and proportion of participants developing Acute Kidney Disease (Kidney dysfunction lasting 7-90 days after AKI or de novo). [Time frame: 6 months]
• Change in Model for End-Stage Liver Disease Sodium (MELD-Na) score- Mean change from baseline in MELD-Na score. [Time frame: 6 months]
• Change in Child-Turcotte-Pugh (CTP) score - Mean change from baseline in Child-Turcotte-Pugh score [Time frame: 6 months]
• Composite liver decompensation outcome- measured as % participants with ≥1 event, Includes: SBP, variceal bleed, hepatic encephalopathy. [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Age > 18 years <80years
• Patient of MASLD/ NAFLD cirrhosis with clinical ascites
• Stable eGFR-(>60 ml/min/1.73m2) calculated using MDRD-6 equation: eGFR (ml/min/1.73 m2) = 170 × (Scr)-0.999 × (Age)-0.176 × (0.762 if patient is female) × (1.180 if black) × (SUN)-0.170 × (Albumin)0.318

Exclusion criteria

• Age <18 years >80 years
• K/C/O systemic hypertension.
• Coagulopathy- INR >2.5
• Post TIPS
• CTP class C
• Any intrinsic/structural kidney disease.
• Refractory Ascites
• Patient with HCC(outside MILAN criteria) or portal vein thrombosis
• Pregnancy or Lactating mother
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
• Patients with anuria, acute renal failure, or Addison's disease
• Heart failure (NYHA II to IV)
• History of hospitalization for hyperkalaemia or acute renal failure induced by previous aldosterone antagonist treatment
• Ongoing drug or alcohol abuse
• Uncontrolled type 2 DM ( HbA1C > 9)
• MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
• Coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\]) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomisation
• Diagnosed Mixed ascites (additional etiology of ascites apart from portal hypertension)
• Patients who are on spirinolactone with stable ascites in the past 12 weeks
• Refusal to give consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

India · 1 center

• Institute of Liver and Biliary Sciences — New Delhi

Identifiers

NCT: NCT07585526 · ILBS-MASLDCKD-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗