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

ISRCTN	ISRCTN52111708
DOI	https://doi.org/10.1186/ISRCTN52111708
Secondary identifying numbers	RG_05-002

Submission date: 19/09/2005
Registration date: 12/10/2005
Last edited: 11/04/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr David Mutimer
Scientific

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

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Hepatitis B immunoglobulin (HBIg) withdrawal from combination lamivudine (LAM)/HBIg prophylaxis in liver transplant recipients
Study acronym	HBIg/ADV
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
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 study start date	01/10/2005
Completion date	01/10/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	120
Key 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
Key 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
Date of first enrolment	01/10/2005
Date of final enrolment	01/10/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Liver Unit

Birmingham
B15 2TH
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Website	http://www.bham.ac.uk
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Industry

Educational Grant from Gilead Sciences Inc

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

11/04/2017: No publications found in PubMed, verifying study status with principal investigator