TDF VS LAM + ADV in LAM + ADV Treated LAM-resistant CHB Patients With Undetectable Hepatitis B Virus DNA

Chronic Hepatitis B Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01732367
• Other study ID #: TDF0001
• Status: Completed
• Phase: Phase 4
• First received: November 19, 2012
• Last updated: October 27, 2016
• Start date: November 2012
• Est. completion date: April 2016

Study information

• Verified date: October 2016
• Source: Keimyung University Dongsan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationKorea: Institutional Review Board
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: April 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Lamivudine plus adefovir
Lamivudine 100mg QD for 96 weeks + Adefovir 10mg QD for 96 weeks
• Tenofovir
Tenofovir 300mg QD for 96 weeks

Locations

Country	Name	City	State
Korea, Republic of	Department of Internal Medicine, Keimyung University Dongsan Medical Center	Daegu

Sponsors (6)

Lead Sponsor	Collaborator
Keimyung University Dongsan Medical Center	Daegu Catholic University Medical Center, DongGuk University, Kyungpook National University, Pusan National University Hospital, Yeungnam University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 96 while on treatment	No
Secondary	Virologic response	Virologic response Percentage number of patients with virus reactivation at Week 48	Week 96 while on treatment	No
Secondary	Antiviral resistance	Antiviral resistance percentage number of patients who developed drug resistant mutation at Week 48 and 96 while on randomized therapy.	Week 96 while on treatment	No
Secondary	Biochemical response	Biochemical response percentage number of patients with biochemical breakthrough at Week 48 and 96	Week 96 while on treatment	No
Secondary	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.	Week 96 while on treatment	No
Secondary	Safety assessment	Safety assessment	Week 96 while on treatment	No