Aspirin for Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

Aspirin for Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized Controlled Trial

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide and a significant public health issue. MASLD may progress to liver cirrhosis and/or hepatocellular carcinoma. Although previous evidence suggests that aspirin has antisteatotic and antifibrotic effects on the liver, a randomized controlled trial assessing long-term efficacy and safety of aspirin in MASLD patients has yet to be conducted. This study aims to conduct a randomized controlled trial to evaluate the efficacy of aspirin in treating MASLD.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Dysfunction Associated Steatotic Liver Disease
• Intervention / Treatment: Drug: Aspirin 81 mg Enteric Coated Tab - 1 tablet; Drug: Placebo

Detailed Description

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most common chronic liver diseases, with an estimated prevalence exceeding 30% globally. MASLD can result in liver cirrhosis, hepatocellular carcinoma (HCC), and death, and it has become the leading cause of HCC waiting for liver transplantation in the U.S. Unfortunately, although several new drugs put forth in clinical trials have been shown to offer certain benefits towards improving MASLD, an effective medicine remains lacking. With the limitations in efficacy and safety issues, even though some medications maybe hopeful in the treatments for MASLD, more medical choices remain highly expected. Emerging laboratory evidence suggests that antiplatelet therapy, e.g., aspirin, can reduce the risk of MASLD progression; however, a well-designed clinical trial should be mandatory before its clinical use. A recently published 6-month, phase 2 randomized controlled trial (RCT) demonstrated that daily aspirin might improve MASLD, but several limitations of this study should be further investigated. Therefore, we aim to conduct a RCT to evaluate the long-term effect of low-dose aspirin therapy on MASLD. This phase 2, double-blind, randomized, placebo-controlled trial will recruit MASLD patients, who fulfill the inclusion and exclusion criteria of this study. Participants will be randomly assigned in a 1:1 ratio to receive daily low-dose (81mg) aspirin or a placebo for 240 weeks. Participants will be follow-up at outpatient clinics every 12 weeks, and liver stiffness measurement (LSM) will be evaluated by using vibration-controlled transient elastography (VCTE). The surrogate primary endpoint is mean absolute change of VCTE-estimated liver stiffness at week 48. The clinical- outcome primary endpoint is MASLD-related outcomes (LSM progression >= 5 kPa, liver decompensation, HCC development, cardiovascular events, and death) at week 240. The secondary endpoints include mean absolute changes of hepatic fat fraction measured by 1H-MR spectroscopy and liver function parameters and the cumulative incidence of bleeding events. Additionally, the study will explore associations between stool microbiota/ MASLD-related single nucleotide polymorphisms, such as PNPLA3, TM6SF2, MBOAT7 genes, and clinical outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Teng-Yu Lee, MD, MBA, PhD; Phone Number: 3301 +886423592525; Email: tylee@vghtc.gov.tw

Study Locations

• Taiwan
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital
    • Contact: Teng-Yu Lee, MD, MBA, PhD; Phone Number: 3301 0423592525; Email: tylee@vghtc.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years of age or older
2. Diagnosed with MASLD, which is defined by the Delphi consensus, with at least one out of five cardiometabolic criteria

Exclusion Criteria:

1. Increased alcohol intake (average ≥ 20 g/day for women and ≥ 30 g/day for men)
2. Glycated hemoglobin (HbA1c) level ≥ 9.0%
3. Other causes of chronic liver disease, such as HBV, HCV, autoimmune hepatitis, Wilson's disease, etc.
4. Liver decompensation (Child-Pugh class B or C)
5. Liver cirrhosis with significant portal hypertension (platelet count < 100,000/mm3, splenomegaly, and/or the presence of esophageal/gastric varices)
6. High-risk EGV, defined as F2, F3, or with red-color signs, diagnosed by endoscopy within 6 months before screening
7. Active peptic ulcer disease diagnosed by endoscopy within 6 months be- fore screening
8. FIB-4 index < 1.3 at screening
9. Indicated for any anti-platelet therapy, such as history of cardiovascular events
10. History of aspirin allergy
11. History of bleeding disorders, such as hemophilia
12. Pregnancy or breast feeding
13. Severe renal impairment, which is defined as eGFR < 30 mL/min/1.73 m²
14. Any malignancies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin arm; Participants will be randomly assigned in a 1:1 ratio to receive daily low-dose (81mg) aspirin or a placebo	Drug: Aspirin 81 mg Enteric Coated Tab - 1 tablet; Participants will be randomly assigned in a 1:1 ratio to receive daily low-dose (81mg) aspirin or a placebo; Other Names: Un-impede E.F.C.
Placebo Comparator: Placebo arm; Participants will be randomly assigned in a 1:1 ratio to receive daily low-dose (81mg) aspirin or a placebo	Drug: Placebo; Participants will be randomly assigned in a 1:1 ratio to receive daily low-dose (81mg) aspirin or a placebo; Other Names: Placebo Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean absolute change of VCTE-estimated LSM	The surrogate primary endpoint is mean absolute change of VCTE-estimated LSM (kPa).	Week 48
Cumulative incidence of MASLD-related clinical outcomes	The clinical-outcome primary endpoint is the cumulative incidence (%) of any MASLD-related adverse outcomes, including LSM progression >= 5 kPa, liver decompensation, HCC development, cardiovascular events, and death.	Week 240

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean percentage change of VCTE-estimated LSM	Mean percentage change of LSM measured by VCTE (%)	Week 48, Week 240
Changes in hepatic fat fraction	Mean change of hepatic fat fraction measured by MRS (%)	Week 48, Week 240
Mean absolute changes of serum AST/ ALT	Mean absolute changes of serum AST, ALT (U/L)	Week 48, Week 240
Mean percentage changes of serum AST/ ALT	Mean percentage changes of serum AST/ ALT (%)	Week 48, Week 240

Collaborators and Investigators

• Sponsor: Taichung Veterans General Hospital
• Investigators: Study Chair: Teng-Yu Lee, MD, MBA, PhD, Taichung Veterans General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: April 6, 2025
• First Submitted That Met QC Criteria: April 12, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Aspirin
• Other Study ID Numbers: CF24404A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No