Condition category
Infections and Infestations
Date applied
07/01/2014
Date assigned
31/03/2014
Last edited
21/06/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Hepatitis B virus (HBV) is a virus which causes long term liver damage in people all over the world. It is very common in much of sub-Saharan Africa and southeast Asia. Some countries have more than 10% of the entire population with the virus. Zambia is a country with a high HBV prevalence – approximately 10%. HBV causes liver cirrhosis and liver cancer after several decades of infection, but now this is preventable. It is known that the best way to treat people who have active HBV infection is to give them powerful drugs that stop the virus replicating. The old drugs that used to be used to treat hepatitis B (such as lamivudine) are very cheap but they are not very powerful and many people develop resistance to them so that they stop working after a period of time. The new drugs that are used to treat hepatitis B are more powerful and most people do not develop resistance. However, the new drugs may have more side effects in the long term and they are much more expensive. In many infections we know that starting treatment with a powerful drug and then reducing the treatment to a weaker drug is very effective. In London a small study of this approach has been tried in patients with hepatitis B with success in most cases. Specifically people who had been treated with the expensive new drug tenofovir and who were responding to treatment were changed to treatment with the weaker, cheaper, probably safer drug lamivudine. The great majority responded very well. The aim of this study is to find out whether this way of treating hepatitis B works in Lusaka, Zambia.

Who can participate?
80 Zambian adults, both sexes and aged 18 years or more, with HBV infection, already with evidence of some liver damage (using a marker in blood called ALT).

What does the study involve?
Participants take tenofovir, the best single drug currently available, for 12 months to suppress the virus, then step down to lamivudine treatment. The evidence suggests that after a period of complete viral suppression lamivudine failure may be much less likely. Participants are monitored very closely during the 6 months after stepping down to lamivudine.

What are the possible benefits and risks of participating?
The main benefit is that participants receive at least 18 months of powerful antiviral therapy. The principal risks are associated with the liver biopsy (bleeding, but only 1 in 3000 have this problem), and the possibility that the infection may flare up aggressively at the end of the study. Past experience suggests that this is very uncommon. If successful, this approach could lead to a much more affordable treatment approach for Africans with HBV infection, of whom there are many tens of thousands.

Where is the study run from?
University Teaching Hospital, Lusaka (Zambia)

When is the study starting and how long is it expected to run for?
January 2014 to September 2017

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
1. Prof. Graham Foster, principal investigator
2. Prof. Paul Kelly and Dr Bright Nsokolo, chief investigators in Lusaka

Trial website

Contact information

Type

Scientific

Primary contact

Prof Graham Foster

ORCID ID

Contact details

Blizard Institute
Barts & The London School of Medicine
Queen Mary University of London
4 Newark Street
London
E1 2AT
United Kingdom
+44 (0)20 7882 7242
g.r.foster@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Step HEP

Study information

Scientific title

Step-down affordable treatment for chronic hepatitis B infection in Africa: feasibility of treatment strategy

Acronym

Step HEP

Study hypothesis

That a treatment regime of tenofovir for 48 weeks followed by lamivudine for 24 weeks effectively suppresses hepatitis B virus (HBV) replication in more than 50% of patients.

Ethics approval

University of Zambia Biomedical Research Ethics Committee, 24/05/2013, ref: 005-02-13

Study design

Single group evaluation of feasibility of treatment strategy

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Hepatitis B infection

Intervention

Patients will be given Tenofovir 300mg daily (orally) for 52 weeks and then lamivudine 100mg (orally) daily for 26 weeks. Patients will be followed up for 6 months after starting lamivudine.

Intervention type

Drug

Phase

Not Applicable

Drug names

Tenofovir, lamivudine

Primary outcome measures

Proportion of patients who successfully step down to lamivudine monotherapy with virological control of replication throughout

Secondary outcome measures

1. Proportion of patients who, even if there is virological rebound, achieve successful control on re-introduction of tenofovir
2. Accuracy of ALT monitoring in comparison with viral load monitoring
3. Accuracy of HBsAg quantification compared to viral load monitoring

The primary and secondary outcomes will be assessed by virological measurements in blood samples obtained every 3 months.

Overall trial start date

06/01/2014

Overall trial end date

01/09/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. HBV viral load >105 copies/ml
2. Alanine aminotransferase (ALT) >1.3 times upper limit of normal (which sets the criterion at 45 i.u./l)
3. Evidence of inflammation on liver biopsy
4. May be either e antigen negative (n=40) or positive (n=40)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

80

Participant exclusion criteria

1. Histological or radiological evidence of cirrhosis
2. HIV infection
3. History of alcohol abuse or histological evidence of alcoholic liver disease
4. History of any long-term drug ingestion
5. Histological evidence of metabolic liver disease (haemochromatosis, Wilson’s disease, a1-antitrypsin deficiency) or autoimmune liver disease [antibodies to M2 antigen, Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), nuclear antigens, microsomes or smooth muscle]
6. Histological or radiological evidence of schistosomiasis
7. Histological evidence of hepatitis D virus (HDV) infection
8. Virological evidence of active hepatitis C virus (HCV) or hepatitis E virus (HEV) infection

Recruitment start date

06/01/2014

Recruitment end date

31/12/2015

Locations

Countries of recruitment

Zambia

Trial participating centre

University Teaching Hospital
Lusaka
-
Zambia

Sponsor information

Organisation

Queen Mary University of London (UK)

Sponsor details

Barts & The London School of Medicine Joint R&D office
Rutland House
New Road
London
E1 2AX
United Kingdom
+44 (0)20 7882 7273
g.collins@qmul.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Research council

Funder name

Medical Research Council (MR/K007394/1)

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

21/06/2017: The overall trial end date was changed from 31/12/2015 to 01/09/2017.