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

Sponsor
The University of Hong Kong
Study ID
NCT05147090
Phase
PHASE4
Status
Active Not Recruiting

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Empagliflozin 10 MG — DRUG
    Empagliflozin 10mg daily
  • Placebo pills — DRUG
    Identical in appearance to empagliflozin 10mg daily

Study Details

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.

Key Dates

Start date
Jan 2, 2022
Status verified
Dec 2025
Primary completion
Dec 31, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
106 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Empagliflozin group
    Empagliflozin 10mg daily for 156 weeks
  • Placebo Comparator: Placebo group
    Placebo pills (identical in appearance to empagliflozin 10mg) daily for 156 weeks

Primary Outcome Measure

Change in liver stiffness (measured by MRE) [ Time Frame: week 156 ]

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