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

February 6, 2023 updated by: Grace Lai Hung Wong, Chinese University of Hong Kong

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

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.

Study Type

Observational

Enrollment (Anticipated)

1800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Shatin, Hong Kong
        • Prince of Wales Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

CHB patients who are receiving TAF or ETV as antiviral therapy for CHB, who were either previously treatment naïve.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CKD at 12 months
Time Frame: 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in eGFR
Time Frame: 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
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2022

Primary Completion (ANTICIPATED)

December 21, 2025

Study Completion (ANTICIPATED)

December 31, 2026

Study Registration Dates

First Submitted

June 13, 2022

First Submitted That Met QC Criteria

June 15, 2022

First Posted (ACTUAL)

June 21, 2022

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 6, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TAF-renal study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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