Chronic Kidney Disease Progression in Chronic Hepatitis B Patients on Tenofovir Alafenamide (TAF) Versus Entecavir

Chronic Hepatitis B Clinical Trial

Official title:

Chronic Kidney Disease Progression in Chronic Hepatitis B Patients on Tenofovir Alafenamide (TAF) Versus Entecavir

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05423834
• Other study ID #: TAF-renal study
• Status: Active, not recruiting
• Start date: September 1, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2023
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). TAF has been approved in the clinical practice guidelines in the west. Since its availability in Asia in 2017, there have been evolving data concerning its positive impact on renal safety as shown in registration trials. The primary objective of this study is to compare the risk of chronic kidney disease (CKD) progression in chronic hepatitis B patients on TAF versus ETV in a territory-wide cohort in Hong Kong.

Description:

Antiviral therapy with nucleos(t)ide analogues (NAs) has revolutionized the management of chronic hepatitis B (CHB) in the last two decades.1 Entecavir (ETV), a nucleoside analogue, is one of the first-line NAs recommended by all international treatment guidelines.2-4 As hepatitis B surface antigen (HBsAg) seroclearance rarely occurs, most patients require long-term, if not life-long, NA therapy. Hence, the safety of NAs requires careful scrutiny. In clinical trials, nephrotoxicity may occur in a small proportion of patients receiving nucleotide analogues. We previously demonstrated that tenofovir disoproxil fumarate (TDF) was associated with mild renal impairment in a minority of patients; those treated with entecavir (ETV) had a similar risk compared to untreated patients.5 Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). TAF has been approved in the clinical practice guidelines in the west. Since its availability in Asia in 2017, there have been evolving data concerning its positive impact on renal safety as shown in registration trials.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1800
• Est. completion date: December 31, 2026
• Est. primary completion date: December 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Positive hepatitis B surface antigen (HBsAg) or documented history of CHB for 6 months or more; AND
• On TAF 25 mg daily as antiviral treatment for CHB (cases); OR
• On ETV 0.5 to 1.0 mg daily as antiviral treatment for CHB (controls)

Exclusion Criteria:

• Previous NA treatment prior to TAF or ETV
• Positive antibody against hepatitis C, D, or human immunodeficiency virus (anti-HCV, anti-HDV, or anti-HIV)
• Evidence of other autoimmune or metabolic liver diseases (except non-alcoholic fatty liver disease).
• Moribund state including advanced/pre-terminal liver cancer or other non-hepatic cancers
• Non-hepatic cancer undergoing chemotherapy within last 6 months

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Disease Progression
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Tenofovir alafenamide
Chronic hepatitis B patients who are receiving TAF as antiviral therapy for CHB, who were previously treatment naïve.
• Entecavir
Chronic hepatitis B patients who are receiving ETV as antiviral therapy for CHB, who were previously treatment naïve.

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Shatin

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (5)

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67 — View Citation

Lo AO, Wong GL. Current developments in nucleoside/nucleotide analogues for hepatitis B. Expert Rev Gastroenterol Hepatol. 2014 Aug;8(6):607-22. doi: 10.1586/17474124.2014.909724. Epub 2014 Apr 30. — View Citation

Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, — View Citation

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan;63(1):261-83. doi: 10.1002/hep.28156. Epub 2015 Nov 13. No ab — View Citation

Wong GL, Chan HL, Tse YK, Yip TC, Lam KL, Lui GC, Szeto CC, Wong VW. Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment. Aliment Pharmacol Ther. 2018 Nov;48(9):984-992. doi: 10.1111/apt.14945. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CKD at 12 months	To evaluate chronic kidney disease (CKD) progression at 12 months. The CKD progression is defined as an increase in CKD stage for at least 1 stage for at least 3 consecutive months during follow-up.	12 months
Secondary	Change in eGFR	calculated using the CKD Epidemiology Collaboration (CKD-EPI) equation expressed as a single equation: GFR (in mL/min/1.73 m2) = 141 × min (Scr /?, 1)a × max(Scr /?, 1)-1.209 × 0.993Age × 1.018 [for the cases of females] × 1.159 [for the cases of ethnic Africans ]; where: Scr is the serum creatinine in mg/dL (equals to serum creatinine in micromole/L /88.4) , ? is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /? or 1, and max indicates the maximum of Scr /? or 1.11 CKD stages 1, 2, 3A, 3B, 4 and 5 were defined based on eGFR	12 months