TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA
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Purpose
| Condition | Intervention | Phase |
|---|---|---|
| Chronic Hepatitis B | Drug: Lamivudine plus adefovir Drug: Tenofovir | Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| 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. |
- 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.
- Virologic response [ Time Frame: Week 96 while on treatment ]Virologic response Percentage number of patients with virus reactivation at Week 48
- Antiviral resistance [ Time Frame: Week 96 while on treatment ]Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy.
- Biochemical response [ Time Frame: Week 96 while on treatment ]Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96
- Serologic response [ Time Frame: Week 96 while on treatment ]Serologic response (1) HBeAg loss/seroconversion in HBeAg-positive CHB Percentage number of patients with HBeAg loss or seroconversion at Week 48 and 96.
- Safety assessment [ Time Frame: Week 96 while on treatment ]Safety assessment
| Enrollment: | 171 |
| Study Start Date: | November 2012 |
| Study Completion Date: | April 2016 |
| Primary Completion Date: | March 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Lamivudine plus adefovir
Continue lamivudine/adefovir add on treatment (standard treatment)
|
Drug: Lamivudine plus adefovir
Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks
Other Names:
|
|
Experimental: Tenofovir
Switch from lamivudine/adefovir add on treatment to tenofovir monotherapy
|
Drug: Tenofovir
Tenofovir 300mg QD for 96 weeks
Other Name: Viread
|
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.
Eligibility
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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
Contacts and Locations
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01732367
| Korea, Republic of | |
| Department of Internal Medicine, Keimyung University Dongsan Medical Center | |
| Daegu, Korea, Republic of, ASI|KR|KS002|TAEGU | |
| Principal Investigator: | Byoung Kuk Jang, M.D | Department of Internal Medicine, Keimyung University Dongsan Medical Center |
More Information
| Responsible Party: | Jang Byoung Kuk, Keimyung University Dongsan Medical Center |
| ClinicalTrials.gov Identifier: | NCT01732367 History of Changes |
| Other Study ID Numbers: |
TDF0001 |
| First Submitted: | November 19, 2012 |
| First Posted: | November 22, 2012 |
| Last Update Posted: | October 28, 2016 |
| Last Verified: | October 2016 |
Keywords provided by Jang Byoung Kuk, Keimyung University Dongsan Medical Center:
|
Tenofovir Lamivudine Adefovir Chronic Hepatitis B |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis, Chronic Hepatitis B Hepatitis B, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections |
DNA Virus Infections Tenofovir Lamivudine Adefovir Adefovir dipivoxil Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |