Chronic Hepatitis BPhase 4NCT01732367
TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA
A Phase 4 study testing Lamivudine plus adefovir and Tenofovir in people with Chronic Hepatitis B, run by Keimyung University Dongsan Medical Center at 1 site in South Korea.
Trial summary
This study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in Lamivudine plus Adefovir Treated Lamivudine-resistant chronic hepatitis B patients with Undetectable Hepatitis B Virus DNA Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Lamivudine plus adefovir and Tenofovir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 171 participants
- Where
- 1 siteSouth Korea
- Study dates
- Nov 2012to Apr 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients aged 18 or older
- The CHB patients (both HBeAg-positive and - negative) who have at least 6 months undetectable HBV DNA (serum HBV DNA ≤ 20 IU/mL) after lamivudine plus adefovir combination therapy.
Who cannot join
- Patients with decompensated liver disease
- Patients with HCV, HDV or HIV
- Patients with HCC
- Serum ALT > 2x ULN level
- Serum creatinine > 2.0mg/dL
- Pregnant or lactating women
Show all 9Show fewer
- Women who have a plan for pregnancy within the three coming years
- Patients who have uncontrolled severe concomitant diseases- severe cardiovascular diseases and other infection
- Those who have no capabilities to understand and sign an informed consent
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Department of Internal Medicine, Keimyung University Dongsan Medical Center
Daegu, ASI|KR|KS002|TAEGU
About this study
Official title: Randomized Trial of Tenofovir Versus Lamivudine Plus Adefovir in Lamivudine Plus Adefovir Treated Lamivudine-resistant Chronic Hepatitis B Patients With Undetectable Hepatitis B Virus DNA.
This study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in Lamivudine plus Adefovir Treated Lamivudine-resistant chronic hepatitis B patients with Undetectable Hepatitis B Virus DNA
Read the detailed description
Recently, in Korea, long-term medication of antiviral agents and their resulting resistance expression have been the most serious cause of failure to treat chronic hepatitis B. Exp.
In particular, the annual resistance rate to lamivudine currently widely being used in Korea amounts to about 15 to 20 percents and the rate is expected to reach 70 to 80 percent in four to five years.
The guidelines by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a combination therapy with adefovir or tenofovir for patients with lamivudine resistant HBV .
In Korea, however, in case of combined prescription of lamivudine and adefovir, only one of them is covered by the health insurance and therefore many patients are difficult to continue treatment due to their economic conditions.
Tenofovir that has been developed most recently and will be placed on sale sooner or later in Korea has strong antiviral effects, causes little or no emergence of resistant viruses, and is known to have lower nephrotoxicity than adefovir.
In particular, several papers reported that tenofovir has effective and sustaining antiviral effects in patients who had other antiviral agents resistant HBV as well as those who received initial treatment. This shows that patients only with lamivudine resistant HBV can be treated only with tenofovir without a combination therapy and when they have low levels of HBV DNA, treatment is relatively effective despite their resistance to adefovir.
Therefore, it is considered that tenofovir switching therapy in patients with undetectable HBV DNA after lamivudine plus adefovir combination therapy to maintain their virus response.
The results of this study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in such patients.
- Conditions
- Chronic Hepatitis B
- Being tested
- Lamivudine plus adefovir, Tenofovir
- Keywords
- Tenofovir, Lamivudine, Adefovir, Chronic Hepatitis B
- 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.
Lamivudine plus adefovirDrug
Also called Zeffix, Hepsera
Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks
TenofovirDrug
Also called Viread
Tenofovir 300mg QD for 96 weeks
| Study group | Role | What they receive |
|---|---|---|
| Lamivudine plus adefovir | Active comparator | Continue lamivudine/adefovir add on treatment (standard treatment) Receives: Drug: Lamivudine plus adefovir |
| Tenofovir | Experimental | Switch from lamivudine/adefovir add on treatment to tenofovir monotherapy Receives: Drug: Tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage number of patients with virus reactivation
Percentage number of patients with virus reactivation (HBV DNA > 40 IU/mL on two consecutive samples taken 1 month apart, or persistent HBV DNA levels of 20-40 IU/mL on three consecutive 1 month interval) at Week 96 while on treatment.
Measured: Week 96 while on treatment
Secondary outcomes (5)
Virologic response
Virologic response Percentage number of patients with virus reactivation at Week 48
Measured: Week 96 while on treatment
Antiviral resistance
Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy.
Measured: Week 96 while on treatment
Biochemical response
Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96
Measured: Week 96 while on treatment
Serologic response
Serologic response (1) HBeAg loss/seroconversion in HBeAg-positive CHB Percentage number of patients with HBeAg loss or seroconversion at Week 48 and 96.
Measured: Week 96 while on treatment
Safety assessment
Safety assessment
Measured: Week 96 while on treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionMar 2016
- Study completionApr 2016
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 Chronic Hepatitis BStudies of the same condition, open and under way.
- 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Keimyung University Dongsan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Kyungpook National University Hospital, Daegu Catholic University Medical Center, DongGuk University, Pusan National University Hospital, Yeungnam University Hospital
- Responsible party
- Principal investigator, Jang Byoung Kuk, Keimyung University Dongsan Medical Center
- Investigators
- Byoung Kuk Jang, M.D, Principal investigator, Department of Internal Medicine, Keimyung University Dongsan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01732367
- Sponsor's protocol ID
- TDF0001
- Status last verified
- Oct 2016
- First submitted
- 19 Nov 2012
- Last updated
- 28 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lee HJ, Kim SJ, Kweon YO, Park SY, Heo J, Woo HY, Hwang JS, Chung WJ, Lee CH, Kim BS, Suh JI, Tak WY, Jang BK. Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients. PLoS One. 2018 Jan 12;13(1):e0190581. doi: 10.1371/journal.pone.0190581. eCollection 2018.
PubMed 29329305
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Tenofovir Versus Lamivudine Plus Adefovir in Lamivudine Plus Adefovir Treated Lamivudine-resistant Chronic Hepatitis B Patients With Undetectable Hepatitis B Virus DNA.
- ClinicalTrials.gov ID
- NCT01732367
- Acronym / sponsor ID
- TDF0001
- Conditions
- Chronic Hepatitis B
- Keywords
- Tenofovir, Lamivudine, Adefovir, Chronic Hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- Keimyung University Dongsan Medical CenterUniversity, hospital or other
- Collaborators
- Kyungpook National University Hospital, Daegu Catholic University Medical Center, DongGuk University, Pusan National University Hospital, Yeungnam University Hospital
- Study start
- Nov 2012
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 22 Nov 2012 (estimated)
- 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.
This study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in Lamivudine plus Adefovir Treated Lamivudine-resistant chronic hepatitis B patients with Undetectable Hepatitis B Virus DNA
Detailed description
Recently, in Korea, long-term medication of antiviral agents and their resulting resistance expression have been the most serious cause of failure to treat chronic hepatitis B. Exp.
In particular, the annual resistance rate to lamivudine currently widely being used in Korea amounts to about 15 to 20 percents and the rate is expected to reach 70 to 80 percent in four to five years.
The guidelines by the American Association for the Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL) recommend a combination therapy with adefovir or tenofovir for patients with lamivudine resistant HBV .
In Korea, however, in case of combined prescription of lamivudine and adefovir, only one of them is covered by the health insurance and therefore many patients are difficult to continue treatment due to their economic conditions.
Tenofovir that has been developed most recently and will be placed on sale sooner or later in Korea has strong antiviral effects, causes little or no emergence of resistant viruses, and is known to have lower nephrotoxicity than adefovir.
In particular, several papers reported that tenofovir has effective and sustaining antiviral effects in patients who had other antiviral agents resistant HBV as well as those who received initial treatment. This shows that patients only with lamivudine resistant HBV can be treated only with tenofovir without a combination therapy and when they have low levels of HBV DNA, treatment is relatively effective despite their resistance to adefovir.
Therefore, it is considered that tenofovir switching therapy in patients with undetectable HBV DNA after lamivudine plus adefovir combination therapy to maintain their virus response.
The results of this study will provide a rationale for switch from lamivudine plus adefovir to tenofovir monotherapy in such patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lamivudine plus adefovir | Active comparator | Drug: Lamivudine plus adefovirContinue lamivudine/adefovir add on treatment (standard treatment) |
| Tenofovir | Experimental | Drug: TenofovirSwitch from lamivudine/adefovir add on treatment to tenofovir monotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male and female patients aged 18 or older
- The CHB patients (both HBeAg-positive and - negative) who have at least 6 months undetectable HBV DNA (serum HBV DNA ≤ 20 IU/mL) after lamivudine plus adefovir combination therapy.
Key exclusion criteria (9 listed)
- Patients with decompensated liver disease
- Patients with HCV, HDV or HIV
- Patients with HCC
- Serum ALT > 2x ULN level
- Serum creatinine > 2.0mg/dL
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 |
|---|---|---|
| Lamivudine plus adefovirAlso: Zeffix, HepseraLamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks | Drug | Lamivudine plus adefovir |
| TenofovirAlso: VireadTenofovir 300mg QD for 96 weeks | Drug | Tenofovir |
Primary outcome
Percentage number of patients with virus reactivation
Time frame: Week 96 while on treatment
Percentage number of patients with virus reactivation (HBV DNA > 40 IU/mL on two consecutive samples taken 1 month apart, or persistent HBV DNA levels of 20-40 IU/mL on three consecutive 1 month interval) at Week 96 while on treatment.
5 secondary outcomes
Virologic response
Time frame: Week 96 while on treatment
Antiviral resistance
Time frame: Week 96 while on treatment
Biochemical response
Time frame: Week 96 while on treatment
Serologic response
Time frame: Week 96 while on treatment
Safety assessment
Time frame: Week 96 while on treatment
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 28 Oct 2016.
- Derived from this study: PubMed 29329305Lee HJ, Kim SJ, Kweon YO, Park SY, Heo J, Woo HY, Hwang JS, Chung WJ, Lee CH, Kim BS, Suh JI, Tak WY, Jang BK. Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients. PLoS One. 2018 Jan 12;13(1):e0190581. doi: 10.1371/journal.pone.0190581. eCollection 2018.
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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.
Byoung Kuk Jang, M.D principal investigator
Department of Internal Medicine, Keimyung University Dongsan Medical Center
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 Lamivudine plus adefovir and Tenofovir in people with Chronic Hepatitis B, run by Keimyung University Dongsan Medical Center at 1 site in South Korea.
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 2 inclusion and 9 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 28 Oct 2016. 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 South Korea. 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?
Percentage number of patients with virus reactivation (time frame: Week 96 while on treatment). 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 NCT01732367, 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 28 Oct 2016.