Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RG_05-002
Study information
Scientific title
Hepatitis B immunoglobulin (HBIg) withdrawal from combination lamivudine (LAM)/HBIg prophylaxis in liver transplant recipients
Acronym
HBIg/ADV
Study hypothesis
The aim of this study is 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
Hospitals
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 units 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 measure
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 (if study stopped)
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. Wilsons 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
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
Basic results (scientific)
Publication list