Chinese Herbal Medicine Combined with Entecavir to Reduce the Off-therapy Recurrence Riks in HBeAg-positive Chronic Hepatitis B Patients: a Multi-center, Double-blind, Randomized Controlled Trial in China

Background: Nucleos(t)ide analogs (NAs) are the first-line options against chronic hepatitis B (CHB). NAs produce a potent suppression of viral replication but are associated with tiny opportunity of HBsAg seroclearance and high risks of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study is designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NAs withdrawal.Methods/design: The study is a nationwide, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 120 weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the Experimental group and Control group in a 1:1 ratio. Patients in the experimental group will be prescribed with TCM formulae (Tiao-Gan-Jian-Pi-Jie-Du granule) plus ETV 0.5mg per day for consolidation therapy of 96 weeks. Patients in the control group will be prescribed with TCM granule placebo plus ETV 0.5mg per day for the same course. After the consolidation therapy, all patients will discontinue their trial drugs and closely monitored in the next 24 weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the accumulative rate of CR at the end of this trial.Conclusion: This study is the first of its kind to observe therapeutic effects in respect of reducing recurrence after drug withdrawals after a unified integrative consolidation therapy in CHB population.