A multicenter open-label randomized controlled trial comparing continuing lamivudine treatment with switching from lamivudine to entecavir treatment for the patients with chronic hepatitis B or cirrhosis receiving lamivudine administration without lamivudine-resistant YMDD mutant virus.

UMIN ID: UMIN000000601

Registered date:01/08/2007

Basic Information

• Recruitment status: Complete: follow-up complete
• Health condition(s) or Problem(s) studied: Chronic hepatitis B or cirrhosis
• Date of first enrollment: 2007/01/01
• Target sample size: 120
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

Lamivudine continuing group:Lamivudine (brand name: Zefix) administration 100mg per day orally is continued. If HBV DNA elevates above 4 log copy/ml or YMDD mutant HBV is detected by PCR thereafter, the study is discontinued, and the patients may be treated with additional administration of adefovir dipivoxil (brand name Hepsera) 10 mg per day orally, switching to entecavir treatment 1.0mg per day orally, or continuation of lamivudine administration, according to the decision of the doctor considering the condition of liver.
Switch-to-entecavir arm: Discontinue lamivudine treatment and switch to entecavir (brand name: Baraclude) administration in a daily dose of 0.5mg before retiring at night. If HBV DNA elevates over 4 log copy/ml or YMDD mutant HBV is detected by PCR afterwards, the patient drops out of the study and may be treated with combination therapy of lamivudine 100mg and adefovir dipivoxil 10mg per day orally, or switching to entecavir treatment in a daily dose of 1.0mg orally, considering the condition of liver.

Outcome(s)

• Primary Outcome: (1) Change of HBV DNA level and incidence rate of virological breakthrough, i.e., elevation of HBV DNA more than 1 log copy/ml.(2) HBeAg clearance rate(3) HBeAg seroconversion rate(4) Incidence of YMDD mutant virus(5) Incidence of entecavir-resistance related mutation
• Secondary Outcome: (1)ALT (2)s-Albumin (3)Prothrombin time 3(3)T.Bil (5)Platelets count (6) Ascites (7)Hepatic encephalopathy (8) Child-Pugh score (9) Development or recurrence of hepatocellular carcinoma (10) Precore mutant HBV (11) Core promoter mutant HBV

Key inclusion & exclusion criteria

• Age minimum: 30years-old
• Age maximum: 75years-old
• Gender: Male and Female
• Exclude criteria: (1)The patients who has a history of an allergy against nucleos(t)ide analogues(2)The patients who have received interferon or other nucleoside analogues than lamivudine within 6 months before registration.(3) Pregnant women, or women who are nursing(4)The patients with other chronic liver disease, such as autoimmune hepatitis, primary biliary cirrhosis, alcoholic hepatitis, or chronic hepatitis C.(5)The patients with an uncontrollable heart trouble (myocardial infarction, heart failure, or arrhythmia)(6)The patients with chronic renal failure or chronic respiratory failure(7)The patients who were thought to be inapproriate for this study by the doctor

Related Information

• Primary Sponsor: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
• Source(s) of Monetary Support: None