In earlier clinical studies, when patients who have been on lamivudine (LAM) were switched to adefovir dipivoxil (ADV), some patients developed ALT flares with an elevation of ALT \> 10 x the upper limits of normal (ULN). There were no cases of hepatic decompensation with the flares, however. The transition methods were varied among physicians from no overlapping to overlapping for 1 to 3 months with LAM and ADV. There is still some uncertainty about the optimal approach to switching from LAM to ADV. This study will compare the safety of directly switching to ADV to a protocolled switch after a period of overlap of 12 weeks. This will facilitate pro-active switching in patients on LAM and will also highlight genotypic resistance ahead of phenotypic resistance as a reason to switch patients. Data to date have only been presented as part of a controlled study in patients with clinically evident LAM-resistance. This study will enroll patients who still have serum hepatitis B virus (HBV) DNA suppression whilst receiving LAM.
Chronic HBV infection is an important worldwide cause of morbidity, mortality and source of potential new infections. There are an estimated 350 million carriers of HBV in the world. In China, Southeast Asia and sub-Saharan Africa, as many as 10-15% of the population are chronically infected. In North America and Northern Europe, infection and carrier rates are much lower, usually below 1%. Intermediate carrier rates of 1-5% are found in Southern Europe (e.g., Italy, Greece and Spain), parts of South and Central America, the Middle East and Japan. Persistent infection develops in over 90% of perinatally infected children and in 3-10% of people who become infected after the age of 6 years. Worldwide, it has been estimated that more than one million people die annually due to HBV-related end stage diseases such as cirrhosis and hepatocellular carcinoma. The goal of antiviral therapy for hepatitis B is to reduce a patient's risks for progressive liver disease through prolonged suppression or eradication of HBV infection and to arrest or ameliorate HBV-related liver damage.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Observe the proportion of patients with ALT elevations (> 10 x ULN) at any time over the course of the switch
Time frame: baseline, 3, 6, 9, and 12 months
Study serum HBV DNA levels over time
Time frame: baseline, 3, 6, 9, and 12 months
Study serum ALT levels over time
Time frame: baseline, 3, 6, 9, and 12 months
Study the proportion of patients with YMDD variants at entry
Time frame: baseline, 3, 6, 9, and 12 months
Study the safety during the switching period
Time frame: baseline, 3, 6, 9, and 12 months
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