Chronic Hepatitis BNCT05423834
Chronic Kidney Disease Progression in Chronic Hepatitis B Patients on Tenofovir Alafenamide (TAF) Versus Entecavir
An observational study of Chronic Hepatitis B, run by Chinese University of Hong Kong at 1 site in Hong Kong.
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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Tenofovir alafenamide and Entecavir
- How many people
- 1,800 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Sep 2022to 31 Dec 2026
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: CHB patients who are receiving TAF or ETV as antiviral therapy for CHB, who were either previously treatment naïve.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Chronic Hepatitis B
- Being tested
- Tenofovir alafenamide, Entecavir
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir alafenamideDrug
Chronic hepatitis B patients who are receiving TAF as antiviral therapy for CHB, who were previously treatment naïve.
EntecavirDrug
Chronic hepatitis B patients who are receiving ETV as antiviral therapy for CHB, who were previously treatment naïve.
| Study group | Role | What they receive |
|---|---|---|
| TAF-treated Chronic hepatitis B patients | Chronic hepatitis B patients that treated with Tenofovir alafenamide Receives: Drug: Tenofovir alafenamide | |
| ETV-treated Chronic hepatitis B patients | Chronic hepatitis B patients that treated with Entecavir Receives: Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
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 /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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2022
- Study start1 Sep 2022
- Primary completion21 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 1,800 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Grace Lai Hung Wong, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05423834
- Sponsor's protocol ID
- TAF-renal study
- Status last verified
- Feb 2023
- First submitted
- 13 Jun 2022
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24787673European 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(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
PubMed 28427875Sarin 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, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
PubMed 26563120Terrault 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 abstract available.
PubMed 26566064Wong 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. Epub 2018 Aug 20.
PubMed 30125952
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic Kidney Disease Progression in Chronic Hepatitis B Patients on Tenofovir Alafenamide (TAF) Versus Entecavir
- ClinicalTrials.gov ID
- NCT05423834
- Acronym / sponsor ID
- TAF-renal study
- Conditions
- Chronic Hepatitis B
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,800 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 21 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 21 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 12 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAF-treated Chronic hepatitis B patients | – | Drug: Tenofovir alafenamideChronic hepatitis B patients that treated with Tenofovir alafenamide |
| ETV-treated Chronic hepatitis B patients | – | Drug: EntecavirChronic hepatitis B patients that treated with Entecavir |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- CHB patients who are receiving TAF or ETV as antiviral therapy for CHB, who were either previously treatment naïve.
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir alafenamideChronic hepatitis B patients who are receiving TAF as antiviral therapy for CHB, who were previously treatment naïve. | Drug | TAF-treated Chronic hepatitis B patients |
| EntecavirChronic hepatitis B patients who are receiving ETV as antiviral therapy for CHB, who were previously treatment naïve. | Drug | ETV-treated Chronic hepatitis B patients |
Primary outcome
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.
1 secondary outcome
Change in eGFR
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Results publication: PubMed 24787673Lo 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.
- Results publication: PubMed 28427875European 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(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
- Results publication: PubMed 26563120Sarin 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, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
- Results publication: PubMed 26566064Terrault 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 abstract available.
- Results publication: PubMed 30125952Wong 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. Epub 2018 Aug 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Hepatitis B, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CKD at 12 months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05423834, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.