Efficacy Study of Combined Hepatitis A and Hepatitis B Vaccine to Protect Against Hepatitis B in Hemodialysis Patients

Hepatitis B Clinical Trial

Official title:

Efficacy of Combined Hepatitis A and Hepatitis B (Twinrix) Vaccine Compared With Hepatitis B Vaccine Alone in Providing Seroprotection Against Hepatitis B in Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00186836
• Other study ID #: 2400
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: April 19, 2007
• Start date: November 2004
• Est. completion date: November 2006

Study information

• Verified date: April 2007
• Source: St. Joseph's Healthcare Hamilton
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Does vaccinating hemodialysis patients with Twinrix® (combination vaccine against hepatitis A and hepatitis B) result in a difference in hepatitis B antibody response in comparison to the monovalent hepatitis B vaccine? Hepatitis B infection is an important cause of mortality and morbidity. Current standard vaccination practices have low efficacy levels in patients (eg. hemodialysis patients) who are most susceptible of infection. Efficacy of the two regiments will be studied.

Description:

Hepatitis B virus (HBV) is a human pathogen that causes acute and chronic liver infection. Immunosuppression may be associated with more frequent persistent infection and HBV infections in renal dialysis patients can become chronic. The routes of transmission of the virus is well established; direct percutaneous inoculation of virus via exchange of contaminated blood, blood products, body fluids, and hemodialysis. The Center for Diseases Control and Prevention (CDC) recommends immunization in high-risk groups, including hemodialysis patients. Ninety to ninety five percent of healthy, immunocompent adults develop protective anti-hepatitis B surface antibody (anti-HBs) with a primary series of hepatitis B vaccination, but the overall efficacy in renal dialysis patients is much lower. The proportion of hemodialysis patients who develop a seroprotective antibody even with higher doses of vaccination is a median 64% (range: 34-88%).

Reports suggest that combined vaccination of hepatitis B and hepatitis A (Twinrix®:

combination vaccine containing inactivated hepatitis A and recombinant hepatitis B) may improve immunogenicity in healthy individuals. In one study, comparing Anti-HBs geometric mean titres (GMT) at month 6 of the series, subjects receiving the combined vaccine showed a statistically significant higher response than those who obtained the monovalent vaccines. Other studies also reflect the same trend at varying points in the vaccination series.

Currently, there are 426 patients in the hemodialysis program at St. Joseph’s Healthcare in Hamilton and 324(76%) patients are susceptible to HBV infection.

Our study will determine if the improved immunogenicity observed with combined HAV and HBV vaccine will increase the efficacy of HBV vaccine in hemodialysis patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: November 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Hemodialysis patients

• Age greater than or equal to 18

• Able and willing to give informed consent

• Undetectable Anti-HBs Ab level

Exclusion Criteria:

• Presence of hepatitis BsAg, hepatitis BcAb

• Treatment with IVIg (intravenous immune globulin) within the last 6 months

• Hypersensitivity to components of either vaccine

• Contraindication to intramuscular injections

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Biological:
• Engerix-B and Twinrix

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
St. Joseph's Health Care London

Country where clinical trial is conducted

Canada, 

References & Publications (9)

Abraham B, Baine Y, De-Clercq N, Tordeur E, Gerard PP, Manouvriez PL, Parenti DL. Magnitude and quality of antibody response to a combination hepatitis A and hepatitis B vaccine. Antiviral Res. 2002 Jan;53(1):63-73. — View Citation

Ambrosch F, André FE, Delem A, D'Hondt E, Jonas S, Kunz C, Safary A, Wiedermann G. Simultaneous vaccination against hepatitis A and B: results of a controlled study. Vaccine. 1992;10 Suppl 1:S142-5. — View Citation

Czeschinski PA, Binding N, Witting U. Hepatitis A and hepatitis B vaccinations: immunogenicity of combined vaccine and of simultaneously or separately applied single vaccines. Vaccine. 2000 Jan 6;18(11-12):1074-80. — View Citation

Kallinowski B, Knöll A, Lindner E, Sänger R, Stremmel W, Vollmar J, Zieger B, Jilg W. Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course? Vaccine. 2000 Aug 15;19(1):16-22. — View Citation

Knöll A, Hottenträger B, Kainz J, Bretschneider B, Jilg W. Immunogenicity of a combined hepatitis A and B vaccine in healthy young adults. Vaccine. 2000 Apr 3;18(19):2029-32. — View Citation

Lee MB, Middleton D. Enteric illness in Ontario, Canada, from 1997 to 2001. J Food Prot. 2003 Jun;66(6):953-61. — View Citation

Leroux-Roels G, Moreau W, Desombere I, Safary A. Safety and immunogenicity of a combined hepatitis A and hepatitis B vaccine in young healthy adults. Scand J Gastroenterol. 1996 Oct;31(10):1027-31. — View Citation

Murdoch DL, Goa K, Figgitt DP. Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability. Drugs. 2003;63(23):2625-49. Review. — View Citation

Recommendations for preventing transmission of infections among chronic hemodialysis patients. MMWR Recomm Rep. 2001 Apr 27;50(RR-5):1-43. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepatitis B antibody response at month 7 (Significant antibody response defined as anti-HBs Ab greater than or equal to 10mIU/mL ).
Secondary	Anti-HBs geometric mean response at 7 months.
Secondary	Efficacy of Twinrix® in achieving seroprotection against HAV in hemodialysis patients(Significant antibody response defined as at least 20mIU/mL concentration of anti-HAV.)
Secondary	Frequency of adverse events associated with vaccine administration