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

February 16, 2007 updated by: University Health Network, Toronto

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment

130

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G2N2
        • University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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 Outcome Measures

Outcome Measure
i) Functional Antibody concentration: The titer of functional antibody against the seven pneumococcal serotypes contained in the conjugate vaccine will be determined
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Deepali Kumar, BSc, MSc, MD, FRCP(C), University Health Network, Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Study Completion

January 1, 2009

Study Registration Dates

First Submitted

September 7, 2005

First Submitted That Met QC Criteria

September 7, 2005

First Posted (Estimate)

September 9, 2005

Study Record Updates

Last Update Posted (Estimate)

February 19, 2007

Last Update Submitted That Met QC Criteria

February 16, 2007

Last Verified

September 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04-0450-A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Transplant

Clinical Trials on The polysaccharide vaccine Pneumovax (Merck-Frosst)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mongolia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe