Adefovir Plus Vaccination in Transplant Patients Without Hepatitis B That Receive a Core Antibody Positive Liver

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01146808
• Other study ID #: AAAB8413
• Secondary ID: IN-US-103-0158
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2006
• Est. completion date: September 2012

Study information

• Verified date: August 2021
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Liver Transplantation

Intervention

Drug:
• Adefovir dipivoxil and hepatitis B vaccination
Adefovir 10mg po daily, or adjusted for renal function and option for Hepatitis B vaccination, double dose

Locations

Country	Name	City	State
United States	Center for Liver Disease and Transplantation at Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of de Novo Hepatitis B Infection After Transplant With a Core Antibody Positive Liver	Determined by positive hepatitis B serology (tests positive for HBsAg) and HBV DNA viral load (>40 IU/mL).	Standard of care visits post-transplant for 2 years
Secondary	Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination		12-18 months post transplant
Secondary	Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal		Six months after hepatitis B vaccination (2 years post transplant)

External Links

•   Liver Transplantation information from the NIH