Hepatitis B immunoglobulin (HBIg) withdrawal from combination lamivudine (LAM)/HBIg prophylaxis in liver transplant recipients

• Register: ISRCTN
• Last refreshed on: 8 May 2017
• Main ID: ISRCTN52111708
• Date of registration: 12/10/2005
• Prospective Registration: No
• Primary sponsor: University of Birmingham (UK)
• Public title: Hepatitis B immunoglobulin (HBIg) withdrawal from combination lamivudine (LAM)/HBIg prophylaxis in liver transplant recipients
• Scientific title: Hepatitis B immunoglobulin (HBIg) withdrawal from combination lamivudine (LAM)/HBIg prophylaxis in liver transplant recipients
• Date of first enrolment: 01/10/2005
• Target sample size: 120
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN52111708
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

United Kingdom

Contacts

• Name: David Mutimer

Key inclusion & exclusion criteria

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
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Hepatitis B virus infected liver transplant recipients
Infections and Infestations
Hepatitis B virus infected liver transplant recipients

Intervention(s)

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)

Primary Outcome(s)

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

Secondary Outcome(s)

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

Secondary ID(s)

RG_05-002

Source(s) of Monetary Support

Educational Grant from Gilead Sciences Inc