The Norwegian Nucleoside Analogue Stop Study — Nuc-Stop  

Hepatitis B, Chronic Clinical Trial

Official title: The Norwegian Nucleoside Analogue Stop Study: a Randomized Open-label Trial in HBeAg Negative Chronic Hepatitis B, Aiming at Achieving a Functional Cure.

Status Completed

Clinical Trial Summary

Globally, an estimated 257 million individuals have chronic hepatitis B-virus infection (CHB). In the absence of treatment 15-40% of these will progress to liver cirrhosis and/or hepatocellular carcinoma. Oral antiviral treatment suppresses the virus and improves prognosis, but less than 0.5% per year achieve a "functional cure" (i.e. HBsAg loss). One remaining controversy, therefore, is whether antiviral treatment must continue life-long. Observational studies have assessed stopping antiviral treatment after years of viral suppression; however, HBsAg loss has rarely been seen. But interestingly, a few small trials that chose watchful waiting instead of re-initiation of treatment when reactivation occurred, achieved 40% HBsAg loss during 6 years follow-up.

The present proposal is a randomized controlled trial that will assess the safety, efficacy, and cost-effectiveness of treatment discontinuation - and delayed restart - in HBeAg negative CHB. The study is sufficiently powered to address the hypotheses, and a pilot study that demonstrates feasibility has been performed. Patients will be enrolled at 12 Norwegian hospitals, in addition to our collaborating institution in Ethiopia - the largest CHB treatment center in sub-Saharan Africa. If the study shows that discontinuation is safe and effective, it will directly impact both national and international treatment guidelines.

Main objective:

-To study whether stopping nucleoside analogue (NA) therapy - and delaying re-start - can trigger an immune response and set off a functional cure (viz HBsAg loss)

Secondary objectives:

• Assess whether stopping NA therapy - and delaying re-start - leads to a higher chance of HBsAg loss

• Assess the safety of stopping NA therapy - and delaying re-start - in terms of hepatic decompensation, fibrosis progression, and/or adverse events

• Study whether stopping NA therapy - and delaying re-start - leads to a higher chance of sustained off-therapy immune control (low viral load and normal ALT)

• Assess the quality of life and cost-effectiveness of stopping NA therapy - and delaying re-start

• Identify predictors of HBsAg loss

Clinical Trial Description

n/a

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic

• NCT number: NCT03681132
• Study type: Interventional
• Source: Oslo University Hospital
• Status: Completed
• Phase: Phase 4
• Start date: September 20, 2018
• Completion date: January 31, 2023