NCT04102176

Halting Nucleoside Analogues in Chronic Hepatitis B

HALT NUCs: Halting Nucleoside Analogue Therapy in Chronic Hepatitis B

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 120 (actual)
• Sponsor: Seng Gee Lim · Academic / Other
• Sex: All
• Age: 21 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Most patients with Chronic Hepatitis B are on nucleoside analogy (NA) long term, but this leads to HBsAg loss (defined as functional cure) of only 2% at 6 years. Recently a number of studies have shown significant HBsAg loss rates after stopping nucleoside analogues (NA). However, no criteria to select such patients have been evaluated. Consequently, the objective of the study is not only to determine the proportion of patients able to achieve HBsAg loss in those with qHBsAg≤100IU/ml. The study is designed as a randomised control trial with 1:2 parallel arm randomisation to continuing NA or stopping therapy. Patients will be monitored after stopping therapy for Hepatitis B flares and also to document HBsAg loss.

Detailed description

Chronic Hepatitis B (CHB) affects over 250 million persons and is considered one of the major causes of mortality and morbidity globally. Standard treatment consists of nucleos(t)ide analogues (NA) or peginterferon (PEG). There has been increasing interested in HBsAg loss, defined as functional cure. However this has been difficult to achieve with NA, and although rates of HBsAg loss are higher with PEG, they are still \<10%. However, a number of studies have shown that HBsAg loss rates were significantly higher in those who stopped NA. A study from Greece by Hadziyannis had a 39% HBsAg loss after patients stopped adefovir therapy. Further studies have shown similar results, and those not able to clear HBsAg have had quiescent disease, although some patients had to restart therapy usually due to hepatitis B flares. No deaths have been reported. Consequently, while stopping therapy has led to HBsAg loss in some patients, it is not clear which patients would benefit the most. The prior studies have indicated that patients most likely to lose HBsAg had low qHBsAg levels and a level ≤100 IU/ml had a high possibility of HBsAg loss. Consequently, we propose to test whether patients with CHB on NA \>1year and without liver cirrhosis and with qHBsAg≤100 IU/ml are able to lose HBsAg compared to those who continue NA. The study is designed as a parallel arm RCT randomised 1:2 to continue NA versus stop NA. Patients will be monitored regularly for clinical status, virological markers, and liver markers. The primary endpoint is HBsAg loss at the end of the study in those who stop versus those who continue NA. Additional outcomes will be hepatitis B flares, inactive hepatitis B status, virological relapse, and restarting therapy.

Conditions

• Chronic Hepatitis B

Interventions

Type	Name	Description
OTHER	stopping nucleos(t)ide therapy	patients taking nucleoside(t)ide therapy will stop treatment
OTHER	Continue nucleos(t)ide analogue	Continue nucleos(t)ide analogue

Timeline

• Start date: 2019-01-29
• Primary completion: 2026-02-01
• Completion: 2026-02-01
• First posted: 2019-09-25
• Last updated: 2025-07-14

Locations

1 site across 1 country: Singapore