Pneumonia Vaccine in Liver Transplant Recipients: a Booster Strategy Using a Conjugate Vaccine

Transplant Clinical Trial

Official title:

Immunogenicity of Pneumococcal Vaccine in Liver Transplant Recipients Using a Conjugate-Polysaccharide Priming-Booster Strategy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00152802
• Other study ID #: 04-0450-A
• Status: Active, not recruiting
• Phase: Phase 4
• First received: September 7, 2005
• Last updated: February 16, 2007
• Start date: January 2005
• Est. completion date: January 2009

Study information

• Verified date: September 2005
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The trial will compare a group of patients whose immune system is primed with the pneumococcal conjugate vaccine and then given a boost with polysaccharide vaccine (prime-boost strategy) vs. a group vaccinated with the standard 23-valent polysaccharide vaccine alone. It is hypothesized that the conjugate vaccine priming will provide an enhanced response in these immunosuppressed individuals who may respond poorly to standard vaccination.

Description:

OBJECTIVE: Responses to 23-valent polysaccharide pneumococcal vaccine (PPV23) are poor in organ transplant recipients. We have recently shown that the conjugate pneumococcal vaccine (PCV7) is immunogenic in this population but responses remain suboptimal. This is a clinical study designed to assess the immunogenicity of a novel pneumococcal vaccination strategy in a cohort of adult liver transplant recipients. The trial will compare a group of patients primed with the pneumococcal conjugate vaccine plus polysaccharide boost with a group primed with placebo plus the standard 23-valent polysaccharide vaccine.

Specific objectives of this study are:

• To determine the quantitative antibody response using both vaccine strategies

• To determine the functional antibody response by the opsonophagocytic assay. This assay has the advantage of assessing if patient antibody responses represent truly functional antibodies that display opsonic activity against pneumococcus and is likely better correlated with protective efficacy.

• To determine the durability of response over two years In addition, the safety of the conjugate vaccine and a determination of whether time from transplant affects response to vaccination will be made.

HYPOTHESIS: It is hypothesized that the PCV7 priming will provide an enhanced response in these immunosuppressed individuals who may respond poorly to standard vaccination.

RESEARCH PLAN: We will enroll 130 liver transplant recipients from the out-patient transplant clinics at Toronto General Hospital, Toronto, Ontario. Recipients who have had pneumococcal vaccination in the past 5 years will be excluded. Upon enrolment, patients will be randomized to receive either placebo or PCV7 in a blinded fashion. Eight weeks later, all subjects will receive PPV23. Serum will be obtained at baseline, 8 weeks, 16 weeks, 6, 12, 18, and 24 months. Sera will be used to perform antibody testing to seven pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F). The baseline, 8, and 16 week sera will be used for opsonophagocytic assay to the above seven serotypes. A baseline nasopharyngeal swab will also be obtained to look for colonization with Streptococcus pneumoniae. Patient recruitment is expected to take two years and follow-up of all patients should be complete by year 3. An additional 4 months will be needed to complete all laboratory testing. The primary outcome will be anticapsular antibody concentration at 16 weeks. A serotype response will be defined as a 2-fold or greater rise in titer from the 8 week concentration. A vaccine response will be defined as response to at least one serotype of the seven measured.

FUTURE DIRECTIONS: Results of this trial will help to develop a rational and optimal pneumococcal vaccination strategy that would prevent significant morbidity in organ transplant recipients. We are currently studying the impact of pneumococcal disease in transplantation by: (i) a review of invasive pneumococcal disease in transplant recipients in Toronto-Peel region to determine incidence and predominating serotypes; (ii) a Canadian survey of vaccination practices in transplantation; (iii) a 3-year follow-up study to determine the sustainability of immune response to pneumococcal vaccine in renal transplant patients previously enrolled in a vaccine trial. We hope that these studies will form the basis of pneumococcal vaccination recommendations for organ transplant recipients.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

Male or female outpatients who fulfill the following criteria will be eligible for the study:

• Liver transplant recipients greater than 3 months post-transplant

• No prior pneumococcal vaccination within the last 5 years

• Stable allograft function as evidenced by a alanine aminotransferase <10 times the upper limit of normal (mmol/L) that is not worsening

• Able to provide written informed consent and comply with study protocol

• Age > 16

Exclusion Criteria:

• Unable to provide informed consent or comply with protocol

• Prior pneumococcal vaccination within 5 years of enrolment

• Splenectomy

• Admitted to hospital for acute illness

• Febrile illness in the past 2 weeks

• Intravenous Immunoglobulin in the last 6 months

• Current episode of allograft rejection

• Currently on full-dose anticoagulation as a contraindication to intramuscular injection

Study Design

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

Related Conditions & MeSH terms

• Transplant

Intervention

Biological:
• The polysaccharide vaccine Pneumovax (Merck-Frosst)

• The conjugate vaccine used will be Prevnar (Wyeth vaccines)

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody titres to the seven serotypes contained in conjugate vaccine (4, 6B, 9V, 14, 19F, 23F) measured at baseline, 8 and 16 weeks. Primary outcome measure will be the anticapsular antibody concentration at 16 weeks.
Secondary	i) Functional Antibody concentration: The titer of functional antibody against the seven pneumococcal serotypes contained in the conjugate vaccine will be determined
Secondary	ii) Adverse Reactions: Any adverse effects attributed to conjugate or polysaccharide vaccines will be documented. These will include local reactions such as redness, swelling, tenderness and systemic reactions such as fever.
Secondary	iii) Invasive Pneumococcal Disease: The study is not sufficiently powered to look at differences in pneumococcal disease between the two groups. However, any occurrence of documented pneumococcal disease in vaccinated patients will be recorded.