Clinical trial NCT01146808: Adefovir Plus Vaccination in Transplant Patients Without Hepatitis B That Receive a Core Antibody Positive Liver
Official title: Prevention of de Novo Hepatitis B Infection With Adefovir Dipivoxil (ADV) and Hepatitis B Vaccination in HBsAg Seronegative Recipients of Liver Grafts From Hepatitis B Core Antibody Positive (HBcAb+) Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis B
Liver Transplantation
Keywords: Vaccination
Immunocompromised Host
Antiviral Agents
Drug Resistance, Viral
Resource Allocation
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2010-06-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the efficacy of adefovir (ADV) in preventing de novo Hepatitis B in patients who receive Hepatitis B core antibody (HBcAb) positive grafts but who are not Hepatitis B Surface antigen (HBsAg) positive prior to transplant (Hepatitis B naive patients). The second objective is to evaluate the efficacy of accelerated vaccination with Hepatitis B in inducing innate immunity, thereby obviating the need for life-long antiviral therapy.

Detailed description: The investigators will conduct a prospective, open-label study of Hepatitis B naive patients who received HBcAb + livers and adefovir prophylaxis post-transplant. At one year to 18 months following transplantation, all study patients will then be vaccinated with standard Hepatitis B vaccine at double dose on a monthly basis for three months, at which point they will be tested for Hepatitis B surface antibody (HBsAb). Any study patients that have developed a sufficient antibody response (HBsAb \>500 IU) will be given the option to discontinue anti-viral treatment in a monitored setting.

Eligibility criteria: Inclusion Criteria:

* Recipients who do not have evidence of hepatitis B surface antigen, regardless of HBcAb and HBsAb status, who:

  1. received liver transplantation with hepatitis B core antibody positive (and HBsAg negative) grafts,
  2. received adefovir treatment post transplantation, and
  3. who have not reached the 18 month post transplantation time period.

Exclusion Criteria:

* Recipients with hepatitis B surface antigen positivity prior to liver transplant.
* Grafts from hepatitis B surface antigen positive patients.
* Previous intolerance to ADV therapy
* Recipients with pre-transplant creatinine \> 1.6 mg/dL
* Patients younger than 21 years of age
* Patients who are pregnant or breastfeeding

Primary outcomes:
measure: Development of de Novo Hepatitis B Infection After Transplant With a Core Antibody Positive Liver
timeFrame: Standard of care visits post-transplant for 2 years
Secondary outcomes:
measure: Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination
timeFrame: 12-18 months post transplant
measure: Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal
timeFrame: Six months after hepatitis B vaccination (2 years post transplant)
Other outcomes:
Locations:
city: New York
country: United States
facility: Center for Liver Disease and Transplantation at Columbia University Medical Center
state: New York
Study officials:
affiliation: Center for Liver Disease and Transplantation at Columbia University Medical Center
name: Robert S Brown, Jr, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, Melzer JS, Roberts JP, Tomlanovich SJ, Vincenti F, et al. The risk of transmission of hepatitis B from HBsAg(-), HBcAb(+), HBIgM(-) organ donors. Transplantation. 1995 Jan 27;59(2):230-4.
citation: Saab S, Chang AJ, Comulada S, Geevarghese SK, Anselmo RD, Durazo F, Han S, Farmer DG, Yersiz H, Goldstein LI, Ghobrial RM, Busuttil RW. Outcomes of hepatitis C- and hepatitis B core antibody-positive grafts in orthotopic liver transplantation. Liver Transpl. 2003 Oct;9(10):1053-61. doi: 10.1053/jlts.2003.50208.