Condition category
Infections and Infestations
Date applied
19/09/2005
Date assigned
12/10/2005
Last edited
18/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr David Mutimer

ORCID ID

Contact details

Liver Unit
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RG_05-002

Study information

Scientific title

Acronym

HBIg/ADV

Study hypothesis

Combination prophylaxis with lamivudine and HBIg is now the standard of care for most, if not all, liver transplant recipients. There are problems associated with HBIg. It is expensive, protocols for HBIg vary, and compliance of medical staff and patients with complex protocols can be poor. Furthermore, in some countries, ongoing supplies of HBIg are not guaranteed.

It is proposed to evaluate the safety of HBIg withdrawal from patients who are receiving combination lamivudine/HBIg following liver transplantation. The proposed study design will examine the following hypotheses:
1. It is safe to withdraw HBIg from the existing prophylaxis regime for recipients who had a low pre-treatment serum HBV titre.
2. Combination lamivudine and adefovir dipivoxil will provide a safe alternative to lamivudine and HBIg prophylaxis for recipients who had a high pre-treatment serum HBV titre.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

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

Condition

Hepatitis B virus infected liver transplant recipients

Intervention

Patients will be stratified into two groups according to the pre-lamivudine treatment, pre-transplantation serum HBV DNA titre (baseline viral load):

Stratum A: in high-risk patients: HBV DNA more than or equal to 1.0 x 10^6 genomic copies/ml or patients who had detectable serum HBV DNA measured with hybridisation assays. (Patients who have not serum HBV DNA measured before commencement of lamivudine treatment may be included in the study, but must enter stratum A).
Patients will be randomised (1:1) into two groups:
Arm 1: LAM 100 mg QD + HBIg (according to each participating unit’s existing protocol) for 2 years, with ADV being used as a rescue therapy
Arm 2: LAM 100 mg QD + ADV 10 mg QD for 2 years

Stratum B: in low-risk patients (HBV DNA less than 1.0 x 10^6 genomic copies/ml)
Arm 3: LAM 100 mg QD only for 2 years (ADV will function as a rescue medication after withdrawal of HBIg)

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The incidence of emergence of detectable serum HBV DNA during prophylaxis (more than or equal to 200 copies/ml HBV DNA).

Secondary outcome measures

The response of serum HBV DNA and outcome of HBV infection for those patients who require adefovir dipivoxil rescue

Overall trial start date

01/10/2005

Overall trial end date

01/10/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or female patients 18 to 75 years of age
2. Patients with serum HBsAg negativity and HBV DNA negativity (<200 copies/mL as per Roche COBAS AMPLICOR HBV MONITOR)
3. Patients have received a liver transplantation and have been successfully treated with lamivudine and HBIg for at least 12 months
4. Females of childbearing potential must have a negative urine pregnancy test at screening. Pre-menopausal females who are using effective methods of contraception and who agree to continue to do so for the duration of the study medication dosing and for 30 days after the last dose of study medication will be able to participate. Post-menopausal females will be eligible for enrollment
5. Confirmation that sexually active males must be practicing acceptable methods of contraception (vasectomy, condom, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period
6. Able to give written informed consent and comply with the requirements of the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

120

Participant exclusion criteria

1. Lactating females or females with a positive pregnancy test
2. History of hypersensitivity to HBIg, lamivudine or adefovir dipivoxil. HCV, hepatitis delta virus (HDV), and/or human immunodeficiency virus (HIV) seropositive
3. Evidence of active liver disease due to other causes (e.g. Wilson’s disease, hemochromatosis, autoimmune hepatitis, hepatitis C or hepatitis D co-infection, known HIV positivity, alpha-1 antitrypsin deficiency, alcoholic liver disease, obesity-induced liver disease, drug-related liver diseases)
4. Previous participation in an investigational trial involving administration of any investigational compound within 3 months prior to the study screening
5. Clinically relevant alcohol or drug use or history of alcohol or drug use considered by the investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events
6. Therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cis-platin, pentamidine) or competitors of renal excretion (e.g. probenecid) within 2 months prior to study screening or the expectation that subject will receive these during the course of the study, unless clinically mandated
7. The use of antiviral therapy with agents demonstrating potential anti-HBV activity within the previous 3 months (e.g. adefovir dipivoxil, famciclovir, lobucavir, emtricitabine, DAPD, LFMAU, entecavir, ganciclovir, tenofovir or others), other than lamivudine and HBIg

Recruitment start date

01/10/2005

Recruitment end date

01/10/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Liver Unit
Birmingham
B15 2TH
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

http://www.bham.ac.uk

Funders

Funder type

Industry

Funder name

Educational Grant from Gilead Sciences Inc

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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