SGLT2i to Prevent of Liver Complications in Patients With CHB and Diabetes Mellitus

NCT06364930 | Recruiting Phase 4

• 1 other identifier: SGLT2i_HBV Study
• Study Type: interventional
• Target: 412
• Locations: 1 country
• Sites: 1

Brief Summary

This is a five-year, double blinded, randomised trial of dapagliflozin versus placebo in patients with chronic hepatitis B and DM or IFG complicated with compensated advanced chronic liver disease (cACLD). 412 subjects will be recruited. Subject will be randomly assigned to receive dapagliflozin 10mg daily or dapagliflozin placebo one tablet daily for up to 5 years. After randomization, subject will be followed up at month 3, month 6 and then 6-monthly until 60 months (follow up ± 4 weeks from scheduled clinic visit is allowed). At each visit, drug compliance, physical examination, observed or reported adverse events will be assessed. 10ml of blood will be taken at each visit and transient elastography to assess fibrosis regression will be performed at 60th month or at withdrawal visit. You are discouraged to use (pegylated)-interferon, any other NA including lamivudine, adefovir, and telbivudine, another SGLT2i Empagliflozin (Jardiance), Dapagliflozin + Metformin XR (Xigduo).

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is liver complications

  defined as HCC and any cirrhotic complications, namely ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, hepatic encephalopathy, and/or hepatorenal syndrome (HRS).

  60 months

Secondary Outcomes (4)

• Cardiovascular complications

  60 months

• change in liver stiffness measurement

  60 months

• change anthropometric parameters (body weight)

  60 months

• change anthropometric parameters (waist-hip ratio)

  60 months

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

10mg QD for 60 months

Drug: Dapagliflozin 10mg Tab

Placebo

PLACEBO COMPARATOR

10mg QD for 60 months

Drug: Placebo 10mg Tab

Interventions

Placebo 10mg Tab DRUG

Placebo 10mg Tab QD for 60 months.

Placebo

Dapagliflozin 10mg Tab DRUG

Dapagliflozin 10mg Tab QD for 60 months.

Dapagliflozin

Eligibility Criteria

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

You may qualify if:

• Patients with chronic hepatitis B on ETV, TDF or TAF monotherapy for at least 12 months.
• Known or newly diagnosed type 2 diabetes mellitus (T2D), defined as HbA1c ≥5.7% or fasting blood sugar ≥5.6 mmol/L, or random blood sugar ≥11.1 mmol/L, or 2 hours sugar after oral glucose tolerance test ≥7.8 mmol/L.
• Stable use of anti-diabetic drugs in the last three months.
• Presence of compensated advanced chronic liver disease (cACLD) with liver stiffness measurement \>10.0 kPa, or significant portal hypertension (spleen stiffness measurement \> 41.3 kPa), or presence any sign of portal hypertension (e.g. splenomegaly, ascites, varices)
• Aged 18 years old or above.
• Written informed consent obtained.

You may not qualify if:

• Patients with hepatitis C virus (HCV) infection as indicated by a positive antibody to HCV (anti-HCV) serology test.
• Patients with history of cirrhotic complications or hepatocellular carcinoma
• Patients with organ transplantation
• Patients receiving a SGLT2i
• Contraindications to SGLT2i due to renal insufficiency (GFR \< 45 mL/min/1.73m2)
• Poor glycaemic control with HbA1c \>9.0%
• Use of multiple anti-diabetic drugs (3 or more)
• Change in anti-diabetic drugs in the last three months.
• Serious medical illnesses or malignancy
• Age \< 18 years
• No patient consents

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (10)

• Sarin SK, Kumar M, Eslam M, George J, Al Mahtab M, Akbar SMF, Jia J, Tian Q, Aggarwal R, Muljono DH, Omata M, Ooka Y, Han KH, Lee HW, Jafri W, Butt AS, Chong CH, Lim SG, Pwu RF, Chen DS. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2020 Feb;5(2):167-228. doi: 10.1016/S2468-1253(19)30342-5. Epub 2019 Dec 15. Erratum In: Lancet Gastroenterol Hepatol. 2020 Mar;5(3):e2. doi: 10.1016/S2468-1253(20)30021-2.

  BACKGROUND

• Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019 Aug;23(3):401-416. doi: 10.1016/j.cld.2019.04.002. Epub 2019 Jun 1.

  PMID: 31266616 BACKGROUND

• GBD 2016 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1345-1422. doi: 10.1016/S0140-6736(17)32366-8.

  PMID: 28919119 BACKGROUND

• Baik D, Kim BW, Oh JK, Kim KA, Ki M. Costs of viral hepatitis B in the Republic of Korea, 2002-2015. J Viral Hepat. 2020 Feb;27(2):156-167. doi: 10.1111/jvh.13219. Epub 2019 Nov 14.

  PMID: 31638305 BACKGROUND

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Shrikrishnapalasuriyar N, Shaikh A, Ruslan AM, Sharaf G, Udiawar M, Price DE, Stephens JW. Dapagliflozin is associated with improved glycaemic control and weight reduction at 44 months of follow-up in a secondary care diabetes clinic in the UK. Diabetes Metab Syndr. 2020 May-Jun;14(3):237-239. doi: 10.1016/j.dsx.2020.03.007. Epub 2020 Mar 26.

  PMID: 32247210 BACKGROUND

• Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK. Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus. Dig Dis Sci. 2020 Feb;65(2):623-631. doi: 10.1007/s10620-019-5477-1. Epub 2019 Jan 25.

  PMID: 30684076 BACKGROUND

• Leiter LA, Forst T, Polidori D, Balis DA, Xie J, Sha S. Effect of canagliflozin on liver function tests in patients with type 2 diabetes. Diabetes Metab. 2016 Feb;42(1):25-32. doi: 10.1016/j.diabet.2015.10.003. Epub 2015 Nov 11.

  PMID: 26575250 BACKGROUND

• Carretero Gomez J, Ena J, Segui Ripoll JM, Carrasco-Sanchez FJ, Gomez Huelgas R, Casas Rojo JM, Suarez Tembra M, Carabantes Rueda JJ, Arevalo Lorido JC. Effect of newer antihyperglycemic drugs on liver steatosis indices in patients with diabetes and obesity. Curr Med Res Opin. 2021 Nov;37(11):1867-1873. doi: 10.1080/03007995.2021.1965563. Epub 2021 Aug 28.

  PMID: 34357836 BACKGROUND

• Adamstein NH, Cornel JH, Davidson M, Libby P, de Remigis A, Jensen C, Ekstrom K, Ridker PM. Association of Interleukin 6 Inhibition With Ziltivekimab and the Neutrophil-Lymphocyte Ratio: A Secondary Analysis of the RESCUE Clinical Trial. JAMA Cardiol. 2023 Feb 1;8(2):177-181. doi: 10.1001/jamacardio.2022.4277.

  PMID: 36449307 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

dapagliflozin

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

Study Officials

• Grace LH Wong, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angel ML Chim, MSc

CONTACT

+85235054205; angelchim@cuhk.edu.hk

Grace LH Wong, MD

CONTACT

+85235053538; wonglaihung@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 15, 2024
• Study Start: March 26, 2024
• Primary Completion (Estimated): October 31, 2030
• Study Completion (Estimated): March 30, 2031
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)