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

Brief Summary

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”

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.

  • Study Type: Interventional
  • Study Design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: July 2012

Detailed Clinical Trial 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.

Interventions Used in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: ADV plus hepatitis B vaccination

Outcome Measures for this Clinical Trial

Primary Measures

  • Development of de novo hepatitis B infection after transplant with a core antibody positive liver
    • Time Frame: Standard of care visits post-transplant for 2 years
      Safety Issue?: Yes

Secondary Measures

  • Proportion of patients with a sustained hepatitis B surface antibody titer > 500 IU/mL prior to and after vaccination
    • Time Frame: 12-18 months post transplant
      Safety Issue?: Yes
  • Proportion of patients who develop de novo hepatitis B infection post ADV withdrawal, which will be assessed at 6 months post withdrawal
    • Time Frame: Six months after hepatitis B vaccination (2 years post transplant)
      Safety Issue?: Yes

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Columbia University
  • Collaborator
    • Gilead Sciences
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Robert S Brown, Jr, MD, MPH, Principal Investigator, Center for Liver Disease and Transplantation at Columbia University Medical Center

References

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.

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.

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01146808