Effects of Empagliflozin on Fibrosis and Cirrhosis in Chronic Hepatitis B Patients

NCT05147090 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: UW-21023
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic hepatitis B (CHB) affects 257million individuals worldwide. In 2017, it caused around 39.7 million cases of cirrhosis and 0.4 million cirrhosis-related deaths in 2017. However, there is no specific treatment for liver fibrosis/cirrhosis. Although nucleos(t)ide analogues (NAs) profoundly suppress viral replication, fibrosis/cirrhosis progression can still occur in NA-treated patients. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that may prevent fibrosis/cirrhosis progression by reducing hepatic steatosis/inflammation, dampening renin-angiotensin aldosterone system (RAAS) activation, and reducing fluid retention, effects of which are independent of glycemic control. Clinical studies in diabetic patients show SGLT2 inhibitors reduce hepatis steatosis/inflammation, regress ascites (a cirrhotic complication), and improve liver function parameters and survival prognosis in terms of model for end-stage liver disease (MELD) score. There are currently no randomized controlled trials (RCTs) on role of SGLT2 inhibitors in preventing fibrosis/cirrhosis progression in CHB patients. Magnetic resonance elastography (MRE) and transient elastography (TE) are non-invasive techniques for liver stiffness measurement (LSM), although MRE is more accurate than TE. The investigators propose a double-blind, randomized, placebo-controlled trial to compare effect of empagliflozin (an SGLT2 inhibitor) with placebo (1:1 ratio) in preventing fibrosis progression in both diabetic and non-diabetic NA-treated CHB patients with significant/advanced fibrosis or compensated cirrhosis. 108 patients will be randomly sampled from our pre-existing TE database. Empagliflozin 10mg daily will be given to treatment arm. Placebo pills will be manufactured identical in appearance to empagliflozin. Subjects will receive active or placebo pills for three years, and undergo clinical, anthropometric and laboratory assessments (at baseline, weeks 8, 16, and every 4 months thereafter). They will undergo LSM by TE at baseline, end of first, second and third year, and by MRE at baseline and end of third year. Primary outcome is difference in change to liver stiffness (measured by MRE) from baseline between the two groups at the end of third year. The study results will determine whether SGLT2 inhibitors can prevent hepatic fibrosis/cirrhosis progression in NA-treated CHB patients.

Conditions

Chronic Hepatitis b; NAFLD; Cirrhosis; Fibrosis, Liver; Empagliflozin; SGLT2 Inhibitors

Outcome Measures

Primary Outcomes (1)

• Change in liver stiffness (measured by MRE)

  difference in change to liver stiffness from baseline between the two groups at the end of year 3 as measured by MRE

  week 156

Secondary Outcomes (19)

• Remission of significant/advanced fibrosis and cirrhosis

  week 156

• Progression of significant/advanced fibrosis to cirrhosis (measured by MRE)

  week 156

• Progression to decompensated cirrhosis

  week 156

• Change in liver stiffness (measured by transient elastography)

  week 26, 52, 104 and 156

• Change in fat content (measured by transient elastography)

  week 26, 52, 104 and 156

Study Arms (2)

Empagliflozin group

ACTIVE COMPARATOR

Empagliflozin 10mg daily for 156 weeks

Drug: Empagliflozin 10 MG

Placebo group

PLACEBO COMPARATOR

Placebo pills (identical in appearance to empagliflozin 10mg) daily for 156 weeks

Drug: Placebo pills

Interventions

Empagliflozin 10 MG DRUG

Empagliflozin 10mg daily

Also known as: empagliflozin

Empagliflozin group

Placebo pills DRUG

Identical in appearance to empagliflozin 10mg daily

Also known as: placebo

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be recruited if they have significant/advanced fibrosis or cirrhosis confirmed by MRE

You may not qualify if:

• decompensated cirrhosis (variceal bleeding, ascites, hepatic hydrothorax, hepatic encephalopathy),
• portal vein thrombosis,
• alcohol intake \>20g within last 2 years,
• concurrent chronic liver disease (chronic hepatitis C infection, autoimmune hepatitis, Wilson's disease, hemochromatosis, primary biliary cholangitis, drug-induced),
• history of malignancy including hepatocellular carcinoma (HCC),
• pregnancy,
• contraindications to empagliflozin (estimated glomerular filtration rate (eGFR) \<45mL/min/1.73m2, recurrent genitourinary tract infections, gangrene, allergy),
• contraindications to MRI (e.g., claustrophobia, implanted devices with ferromagnetic properties).

Sponsors & Collaborators

• The University of Hong Kong: lead
• Research Grant Council: collaborator

Study Sites (1)

The University of Hong Kong/Queen Mary Hospital

Hong Kong, Hong Kong, China, 852, Hong Kong

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Non-alcoholic Fatty Liver Disease; Fibrosis; Liver Cirrhosis

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fatty Liver

Study Officials

• Ka Shing Cheung, MD, MPH

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The placebo pills will be manufactured in identical appearance to the study drug (empagliflozin)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible subjects will be randomly allocated to either the empagliflozin group or placebo group (i.e. control group)

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 7, 2021
• Study Start: January 2, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 30, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)