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ISRCTN
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ISRCTN52111708
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ClinicalTrials.gov identifier
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Public title
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Hepatitis B Immunoglobulin (HBIg) Withdrawal from Combination Lamivudine (LAM)/HBIg Prophylaxis in Liver Transplant Recipients
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Scientific title
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Acronym
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HBIg/ADV
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Serial number at source
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RG_05-002
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Study hypothesis
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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.
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Lay summary
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Ethics approval
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Not provided at time of registration
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Study design
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Randomised controlled trial
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Countries of recruitment
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United Kingdom
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Disease/condition/study domain
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Hepatitis B virus infected liver transplant recipients
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Participants - inclusion criteria
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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
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Participants - exclusion criteria
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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 three 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 two 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 three months (e.g. adefovir dipivoxil, famciclovir, lobucavir, emtricitabine, DAPD, LFMAU, entecavir, ganciclovir, tenofovir or others), other than lamivudine and HBIg
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Anticipated start date
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01/10/2005
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Anticipated end date
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01/10/2011
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Status of trial
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Completed |
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Patient information material
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Target number of participants
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120
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Interventions
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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 two years, with ADV being used as a rescue therapy
Arm 2: LAM 100 mg QD + ADV 10 mg QD for two 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 two years (ADV will function as a rescue medication after withdrawal of HBIg)
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Primary outcome measure(s)
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The incidence of emergence of detectable serum HBV DNA during prophylaxis (more than or equal to 200 copies/ml HBV DNA).
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Secondary outcome measure(s)
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The response of serum HBV DNA and outcome of HBV infection for those patients who require adefovir dipivoxil rescue.
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Sources of funding
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Educational Grant from Gilead Sciences Inc
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Trial website
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Publications
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Contact name
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Dr
David
Mutimer
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Address
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Liver Unit
Queen Elizabeth Hospital
Edgbaston
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City/town
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Birmingham
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Zip/Postcode
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B15 2TH
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Country
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United Kingdom
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Sponsor
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University of Birmingham (UK)
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Address
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Edgbaston
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City/town
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Birmingham
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Zip/Postcode
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B15 2TT
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Country
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United Kingdom
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Sponsor website:
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http://www.bham.ac.uk
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Date applied
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19/09/2005
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Last edited
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18/08/2006
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Date ISRCTN assigned
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12/10/2005
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