Hepatitis B, ChronicPhase 4NCT03778567
Renoprotective Effects of Telbivudine in Chronic Hepatitis B
A Phase 4 study testing Telbivudine in people with Hepatitis B, Chronic and Chronic Kidney Diseases, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Renal impairment is common in patients with chronic hepatitis B infection. For those taking nucleotide analogues, renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B, Chronic, Chronic Kidney Diseases
- What is being tested?
- Telbivudine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Aug 2013to 31 May 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 - 70 years
- Documented HBsAg positivity for at least 6 months. Patients can be either HBeAg positive AND HBV DNA < 9 log10 copies/mL or HBeAg negative AND HBV DNA < 7 log10 copies/mL
- On combination therapy (lamivudine and tenofovir or lamivudine and adefovir) for at least 1 year
- Documented serum creatinine at least in 2 separate occasions in the last 1 year before recruitment
- MDRD eGFR 30-89ml/min at baseline
Who cannot join
- Concomitant liver disease including chronic hepatitis C and/or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis
- Significant alcohol intake or drug abuse
- Pregnant subjects
- Patients with co-existing significant chronic kidney disease (e.g.post renal transplantation etc.)
- Allergic to any of the medications involved in the study
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site
Department of Medicine, The University of Hong Kong, Queen Mary Hospital
Hong Kong
About this study
Official title: The Effect of Telbivudine on Renal Function in Chronic Hepatitis B Patients With Mild to Moderate Renal Impairment
Renal impairment is common in patients with chronic hepatitis B infection. For those taking nucleotide analogues, renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects. In this prospective study, consecutive CHB patients on combined lamivudine (LAM)+ADV/TDF are switched to LdT+ADV/TDF at recruitment and are followed up for 24 months. Estimated glomerular filtration rate (eGFR) is calculated with the Modification of Diet in Renal Disease (MDRD) equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers are investigated in cultured renal tubular epithelial cell line HK-2.
Read the detailed description
Background
Both CHB and chronic kidney disease are major health issue affecting millions of persons worldwide. Based on a large European multicenter database, the Virgil-database, it is estimated that 15% and 4% of the CHB patients in Europe had mild (GFR 50-80ml/min) and moderate (GFR <50ml/min) renal impairment respectively . These group of patients require special attention as the nucleos(t)ides agents (NA) used in the treatment of CHB are cleared by kidneys and may worsen the kidney function. Recently, a subgroup analysis of the GLOBE study and 4 small prospective studies provide circumstantial evidence on the use of telbivudine (LDT) that can improve renal function in CHB patients. However, there are no prospective, controlled trials to date to evaluate the relationship between LDT and renal function.
Research plan and methodology
This is a prospective study in CHB patients treated with NA and pre-existing mild to moderate renal impairment defined as estimated GFR (eGFR) 30-90ml/min.
Aims
To compare the renal function of patients before and after switching lamivudine to telbivudine.
To determine any adverse events from switching other NA to telbivudine To determine any biochemical and virological change from switching other NA to telbivudine by checking ALT, HBV DNA at baseline, and at weeks 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks To determine any change in 24 hour urinary protein and urinary glucose level To determine the in vitro effects of telbivudine on renal tubular cells
- Conditions
- Hepatitis B, Chronic, Chronic Kidney Diseases
- Being tested
- Telbivudine
- Keywords
- chronic hepatitis B infection, telbivudine, chronic kidney disease, nucleotide analogue
- Medical subject headings
- Hepatitis B, Chronic, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelbivudineDrug
Also called lamivudine is switched to telbivudine
CHB patients who are receiving adefovir or tenofovir disoproxil fumarate are recruited. At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued. The patients are followed-up for 24 months.
| Study group | Role | What they receive |
|---|---|---|
| lamivudine + nucleotide analogue | Other | At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued Receives: Drug: Telbivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal function change
Describe the change in renal function after 108 weeks of telbivudine switch
Measured: 108 weeks
Secondary outcomes (2)
Virologic suppression
Rate of virologic suppression
Measured: 108 weeks
Adverse events
Rate of adverse events
Measured: 108 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start1 Aug 2013
- Primary completion16 Jun 2016
- Study completion31 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by The 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Yuen Man Fung, The University of Hong Kong
- Investigators
- Man-Fung Yuen, DSc, MD, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03778567
- Sponsor's protocol ID
- HKUCTR - 1639
- Status last verified
- Dec 2018
- First submitted
- 12 Dec 2018
- Last updated
- 19 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Mak LY, Liu SH, Yap DY, Seto WK, Wong DK, Fung J, Chan TM, Lai CL, Yuen MF. In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue. Dig Dis Sci. 2019 Dec;64(12):3630-3641. doi: 10.1007/s10620-019-05717-0. Epub 2019 Jul 6.
PubMed 31280390
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Telbivudine on Renal Function in Chronic Hepatitis B Patients With Mild to Moderate Renal Impairment
- ClinicalTrials.gov ID
- NCT03778567
- Acronym / sponsor ID
- HKUCTR - 1639
- Conditions
- Hepatitis B, Chronic, Chronic Kidney Diseases
- Keywords
- chronic hepatitis B infection, telbivudine, chronic kidney disease, nucleotide analogue
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Aug 2013 (actual)
- Primary completion
- 16 Jun 2016 (actual)
- Study completion
- 31 May 2018 (actual)
- First posted
- 19 Dec 2018 (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.
Renal impairment is common in patients with chronic hepatitis B infection. For those taking nucleotide analogues, renal toxicity of adefovir disoproxil (ADV) and tenofovir disoproxil fumarate (TDF) is a significant concern in chronic hepatitis B (CHB) patients. Early observational clinical data suggested that telbivudine (LdT) might have renoprotective effects. In this prospective study, consecutive CHB patients on combined lamivudine (LAM)+ADV/TDF are switched to LdT+ADV/TDF at recruitment and are followed up for 24 months. Estimated glomerular filtration rate (eGFR) is calculated with the Modification of Diet in Renal Disease (MDRD) equation. The effects of LdT on cell viability and expression of kidney injury or apoptotic biomarkers are investigated in cultured renal tubular epithelial cell line HK-2.
Detailed description
Background
Both CHB and chronic kidney disease are major health issue affecting millions of persons worldwide. Based on a large European multicenter database, the Virgil-database, it is estimated that 15% and 4% of the CHB patients in Europe had mild (GFR 50-80ml/min) and moderate (GFR <50ml/min) renal impairment respectively . These group of patients require special attention as the nucleos(t)ides agents (NA) used in the treatment of CHB are cleared by kidneys and may worsen the kidney function. Recently, a subgroup analysis of the GLOBE study and 4 small prospective studies provide circumstantial evidence on the use of telbivudine (LDT) that can improve renal function in CHB patients. However, there are no prospective, controlled trials to date to evaluate the relationship between LDT and renal function.
Research plan and methodology
This is a prospective study in CHB patients treated with NA and pre-existing mild to moderate renal impairment defined as estimated GFR (eGFR) 30-90ml/min.
Aims
To compare the renal function of patients before and after switching lamivudine to telbivudine.
To determine any adverse events from switching other NA to telbivudine To determine any biochemical and virological change from switching other NA to telbivudine by checking ALT, HBV DNA at baseline, and at weeks 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks To determine any change in 24 hour urinary protein and urinary glucose level To determine the in vitro effects of telbivudine on renal tubular cells
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lamivudine + nucleotide analogue | Other | Drug: TelbivudineAt the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 - 70 years
- Documented HBsAg positivity for at least 6 months. Patients can be either HBeAg positive AND HBV DNA < 9 log10 copies/mL or HBeAg negative AND HBV DNA < 7 log10 copies/mL
- On combination therapy (lamivudine and tenofovir or lamivudine and adefovir) for at least 1 year
- Documented serum creatinine at least in 2 separate occasions in the last 1 year before recruitment
- MDRD eGFR 30-89ml/min at baseline
Key exclusion criteria (5 listed)
- Concomitant liver disease including chronic hepatitis C and/or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis
- Significant alcohol intake or drug abuse
- Pregnant subjects
- Patients with co-existing significant chronic kidney disease (e.g.post renal transplantation etc.)
- Allergic to any of the medications involved in the study
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 |
|---|---|---|
| TelbivudineAlso: lamivudine is switched to telbivudineCHB patients who are receiving adefovir or tenofovir disoproxil fumarate are recruited. At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued. The patients are followed-up for 24 months. | Drug | lamivudine + nucleotide analogue |
Primary outcome
Renal function change
Time frame: 108 weeks
Describe the change in renal function after 108 weeks of telbivudine switch
2 secondary outcomes
Virologic suppression
Time frame: 108 weeks
Adverse events
Time frame: 108 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
- Derived from this study: PubMed 31280390Mak LY, Liu SH, Yap DY, Seto WK, Wong DK, Fung J, Chan TM, Lai CL, Yuen MF. In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue. Dig Dis Sci. 2019 Dec;64(12):3630-3641. doi: 10.1007/s10620-019-05717-0. Epub 2019 Jul 6.
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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.
Man-Fung Yuen, DSc, MD, PhD principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Telbivudine in people with Hepatitis B, Chronic and Chronic Kidney Diseases, run by The 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 5 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: finished, as of the sponsor's last update on 19 Dec 2018. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Renal function change (time frame: 108 weeks). 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 NCT03778567, which also lists 1 linked publication.
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 19 Dec 2018.