The Norwegian Nucleoside Analogue Stop Study

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

Conditions

• Hepatitis B, Chronic

Interventions

OTHER

Stop of therapy

The active intervention is to stop antiviral therapy, and delay re-start in the high-threshold group.

Sponsors & Collaborators

• University Hospital, Akershus

  collaborator OTHER

• Addis Ababa University

  collaborator OTHER

• St. Paul's Hospital Millennium Medical College, Ethiopia

  collaborator OTHER

• South-Eastern Norway Regional Health Authority, Norway

  collaborator UNKNOWN

• Bærum Hospital, Norway

  collaborator UNKNOWN

• Drammen Hospital, Norway

  collaborator UNKNOWN

• Tønsberg Hospital, Norway

  collaborator UNKNOWN

• Helse Stavanger HF

  collaborator OTHER_GOV

• Ålesund Hospital, Norway

  collaborator UNKNOWN

• Bodø Hospital, Norway

  collaborator UNKNOWN

• Hvidovre University Hospital

  collaborator OTHER

• Karolinska University Hospital

  collaborator OTHER

• Oslo University Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-09-20

Primary Completion

2023-01-31

Completion

2023-01-31

Countries

• Denmark
• Ethiopia
• Norway
• Sweden

Study Locations