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

Sponsor

Chinese University of Hong Kong (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05423834

Collaborator

(none)

1,800

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: Tenofovir alafenamide Drug: Entecavir

Detailed 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

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1800 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Dec 21, 2025

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
TAF-treated Chronic hepatitis B patients Chronic hepatitis B patients that treated with Tenofovir alafenamide	Drug: Tenofovir alafenamide Chronic hepatitis B patients who are receiving TAF as antiviral therapy for CHB, who were previously treatment naïve.
ETV-treated Chronic hepatitis B patients Chronic hepatitis B patients that treated with Entecavir	Drug: Entecavir Chronic hepatitis B patients who are receiving ETV as antiviral therapy for CHB, who were previously treatment naïve.

Arm

Intervention/Treatment

TAF-treated Chronic hepatitis B patients

Chronic hepatitis B patients that treated with Tenofovir alafenamide

Drug: Tenofovir alafenamide

Chronic hepatitis B patients who are receiving TAF as antiviral therapy for CHB, who were previously treatment naïve.

ETV-treated Chronic hepatitis B patients

Chronic hepatitis B patients that treated with Entecavir

Drug: Entecavir

Chronic hepatitis B patients who are receiving ETV as antiviral therapy for CHB, who were previously treatment naïve.

Outcome Measures

Primary Outcome Measures

CKD at 12 months [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.

Secondary Outcome Measures

Change in eGFR [12 months]
calculated using the CKD Epidemiology Collaboration (CKD-EPI) equation expressed as a single equation: GFR (in mL/min/1.73 m2) = 141 × min (Scr /κ, 1)α × max(Scr /κ, 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) , κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1.11 CKD stages 1, 2, 3A, 3B, 4 and 5 were defined based on eGFR

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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